PROSTATE CANCER...as I see
LEXINGTON MEDICAL CENTER
Commentary:...[NOTE, 17 Sept. 2015: I have not methodically updated this page lately. DO NOT pay attention to my recommendations about specific, named physicians as treaters. AND, some links are now probably broken.]
You may have recently gotten good news about your,
or even a loved one's (with you either being a partner or at least partially in the role of a
caretaker), PSA test results or your prostate biopsy results. If so, that's great for
you.....for now!!! I started this web file many years ago. It is impossible for me to keep this file complete and up to date. So, I have decided to do what I can to maintain it. Some of the issues discussed are timeless. The most rapidly changing issues are (1) when should biopsies be performed and (2) how can one identify the favorable cancers.
While nearly all men would get prostate cancer if
all lived to be 100, NCI SEER data indicates that only about 0.2% of men (2 out of 1000) over age 65 actually
die from prostate cancer.
You still may find the following overview to be of
interest since at least one-third of men over fifty years of age will get (deal with)
prostate cancer in their lifetimes (probably half of those age 60 or older already have prostate
cancer they don't know about). Attempts to screen for this cancer have resulted in 2011 in a
crescendo of controversy. But, troublesomeness is not so much in the decision to screen for
the cancer or not. Over-diagnosis is not the problem; over-treatment is the
If you have, instead, gotten bad news or are
awaiting a final determination, this web area is offered in the hopes of helping you deal
with the situation. I advise that you immediately begin to collect your own information about
your case in your own personal folder because you may be getting more than one opinion. And,
there are neat on-line tools you can use that need such information to calculate an answer to
your question. And, if you have a large extended family or network of church or
other friends you'd like to "keep posted" about the details of your "journey" as you go through
this one of life's trials, check out Caring Bridge (previously linked, above) & create your own free, continually updateable website to
which friends & loved ones can post notes which you & each other can read. Of course,
e-mail lists & social media are other high-tech relationship builders so that those who care can be kept informed.
Before the discussion below, a huge amount of what
follows is about how the "system" goes about placing your cancer situation into one of these
3 pigeon holes of tumor-biology risk (but even this table fails to consider age, other
medical problems [co-morbidities], treatment option risks, and personal
May 2007 Amer. Urological Assn.
(AUA) Expert Panel
PSA=/<10; & either stage T1c or T2a; & Gleason
score/sum 6 or less.
PSA=10-20; or stage T2b (but not qualifying otherwise for higher
risk); or Gleason score/sum 7.
PSA=>20; or stage T2c; or Gleason score/sum 8-10.
***REMEMBER: PROSTATE CANCER IS ALMOST
NEVER A MEDICAL EMERGENCY!***
MOST CASES OF ELEVATED PSA ARE NOT
In most areas of medicine, scientific and
practical research are proposing both new tests and approaches to diagnosis & staging as
well as suggesting the discarding of older ways. Whether being acknowledged world-class
experts in their specialty or being your highly conscientious local specialists, all doctors
grapple with controversy and uncertainty as to what to do or not to do. And, standards of
practice evolve (sometimes to more conservative & other times to the more radical) as we
learn more. Older doctors have seen, hundreds of times, a proposed
latest-most-modern-best-method end up on the waste heap of things later shown to be
undependable. This is true whether considering how to advise you about your elevated PSA or
advise about an actual biopsy diagnosis of prostate cancer.
If I refer to "our program," I mean all (as of
early 2009, only one) of our area urologists who take advantage of the services available at
Lexington Medical Center. Who am I? [disclaimer, again] I have put this site
together primarily for the benefit of friends and relatives who have asked for my input. It is
NOT medical advice. It is not for purposes of soliciting "business". If it can be of help to any
others, so be it.
WHAT IS CANCER?
Cancer comes in hundreds of varieties which tend
to have particular characteristics based on the organ within which it originates.
Pathologists are the physician specialists whose job it is to tell/discern cancer from
non-cancer and determine the specific variety. Cancers all have the common feature of
variably and relatively uncontrolled growth...their cell "engines" are hyper-metabolic.
"Benign" means tissue change or an overgrowth which doesn't, itself, kill. "Cancer" means an
overgrowth known to be able to kill. The ordinary prostate cancer is "acinar" adenocarcinoma;
most pathology reports simply call it "adenocarcinoma". Over 80% of prostate cancer cases
have either multiple cancers in the gland or cancers with small outgrowths away from the main
cancer at the time of cancer diagnosis. And our (the medical system as a whole) ability
to define the ones in that =/< 20% minority which are very localized is largely
WHO HAS PROSTATE
If a maximum of 30% of males over age 50 harbor
prostate cancer from the very earliest to late stages, then about 6250 men in combined
Richland and Lexington counties of South Carolina in 1997 (a total population of 500,000) had
prostate cancer (whether they knew it or not), a prostate cancer prevalence of 1.3% of our
general population. In 1997, 170 were expected to die, and 300 would be newly diagnosed. Of
the remaining 5,780 prostate-cancer-containing men, an unknown proportion are already
diagnosed and known. The unknown remainder proportion of the 5780 are unaware and
undiagnosed! The PSA test may or may not detect them...but this test has made the chances of
detecting cancer early MUCH better! And...be aware...many instances of elevated PSA levels
are not due to cancer [false
positive test] (somewhere between 7-11% of all men tested will have elevated PSA in the
apparent absence of prostate cancer).
Because of PSA testing and the appearance of the
"biopsy guns" that easily produce "biopsy cores" becoming widely used in the early 1990s,
there has been an explosive increase in DIAGNOSIS of prostate cancer that had always been
"out there". It used to be diagnosed mostly when at a metastatic stage and was a fatal
disease. Prior to 1975, SEER data indicated that 3% of men die because of prostate cancer;
and that was also the death rate in 2000. It has been calculated that at least 1,000,000
additional USA men have had a (earlier?) diagnosis of prostate cancer without any decrease in
the death rate (hence the interest in "watch and wait" management, see
HOW MIGHT A PATIENT THINK ABOUT THIS
Especially in prostate diseases...most
particularly as to prostate cancer...the situation is remindful of you and your doctor each
trying to look through a keyhole and decide what all is in the room on the other side of the
door. Your doctor has looked through such key-hole situations thousands of times.
Especially if he/she is conscientious and fascinated by looking into those particular types
of "rooms" (gray-zone situations), he/she will use... as best as possible...his/her own
experience in making the assessment and giving advice. You can help by sharing the
uncertainty and realizing that (rather than black and white answers) there are mostly gray
AM I CURED?
It is important, as I'll note below, that you
remember that statistics should not "rule" your personal, particular case. Upon getting a
full diagnosis, no situation is so bad that it is hopeless. My partner had a friend in
another state who called years ago (about 1997) with the unsettling news that, on seeing a
doctor for back pain, his PSA screening test came back with results of about 140; his
biopsies showed Gleason 5+5=10 cancer. Following treatment, his PSA was undetectable until he
died 7-9 years later of a stroke. Another patient contacted me that he just couldn't get on
with life after treatment because his cancer was 4+4=8 and the "prognosis" was "bad". I asked
what his PSA level was: "It is 0.4...BUT that is up from 0.1!! I'm a dead man! I HAVE to get
DNA tests on my biopsy because, if it's aneuploid, I really am dead!!" I'd like everyone to
remember that a personal cure is a "CURE" until/if there is a recurrence...consider the
concept of : "I'm cured though vulnerable". If there is a recurrence or relapse, a remission
or actual cure is again still medically possible...and on and on. On the other hand, you
might die tomorrow in an automobile wreck! Are you recruiting God to help you cope? Do you have the
services of the Savior (Jesus)? [check out some divine healings]
WHICH ARE YOU?
Some patients want to know a lot about their
situation and be involved in decision making. Others prefer to rely almost totally on their
doctor's direction. Be sure to let your doctor know which type of person you
READING AND PERSONAL
Factors and data valuably used to help in ongoing
decision making in your case may not be useful in giving a prognosis (an estimate of your
odds of beating the cancer). You can become seriously confused if you use prognosis
data/statistics in the place of decision-making data/statistics.
WHO LOOKS OUT FOR
In the evolution of our program, we were all well
aware of the great numbers of apparently conflicting studies as to the success and
complication rates of various types of treatments. It is even considered controversial as to
whether prostate cancer should be diagnosed as early as possible! [An excellent book
addressing this and some other health screening issues is Should I Be Tested For
Cancer?...maybe not and here's why, by H. Gilbert Welch, M. D. , M. P. H.] I think that
prostate cancer should be screened for and diagnosed as early as a particular patient and his
physician think it is prudent to do so. There is no such thing as over-diagnosis (in the
sense of catching cancer too early)! OVERTREATMENT, however, is a real problem in the entire
field of medicine! In fact, statistical information for prostate cancer having been
considered, we still come down to the very highly specific evaluation of a single individual
patient: we direct our pathology & lab with a belief in individualized patient care! Our
thinking is almost the opposite of situations limiting patient choice such as less
knowledgeable medical "gate keepers", insurance companies, corporations, institutions,
government agencies, or other entities requiring strict utilization of their own
cost-effective or research protocols. It helps immeasurably to be under the care of a
urologist interested in cancer & with time to deal with your questions. A highly
significant component of whether "satisfactory results" have been achieved rests on the
satisfaction of you, the patient.
Because of highly varying attitudes of individual
patients toward the issues of cancer, radical surgery, radiation, impotence, pain, and
urinary incontinence, no particular treatment is considered automatically "best" based on age
and presence and supposed extent of cancer, alone. And, even though there are some
outstandingly elite or premier programs in the United States for each type of treatment, it
is absolutely unrealistic to expect that every patient can go to such a program. Even if they
could, expert programs often have very strict research-protocol criteria for entry into a
particular treatment method. Such "premier" programs may feel no ethical, financial, or
brotherhood-of-community need at all to take on your particular case for treatment. And, many
knowledgeable insiders in health care consider (just as the "home team" has certain
advantages in sporting events) that local or near-local care has certain strong advantages.
"Home team" has to do with local, "point-of-service"...not long distance...medical care
SHOULD YOU EVEN BE SCREENED FOR PROSTATE
Americans (and human nature) tend to "want to
know"...they don't believe in "ignorance is bliss". But, be warned: I estimate that less than
one in 5 who have a positive screening test (elevated PSA) will prove to have prostate cancer
by biopsy. Elevations can be due to benign enlargement (BPH), chronic prostatitis
("irritation" in the gland), and several other non-cancerous reasons. "Working up" an
elevated PSA test result can cost you time, worry, and money deciding when, where, how, and
by whom you are going to get to help you get to the bottom of why the PSA is
SCREENING IMPLIES DEALING WITH
If you are then proven to have prostate cancer,
there are a number of different treatments (see below), treatment
combinations, treatment facilities, and treating doctors to choose from...a potential source
of worry and confusion. Some authorities feel that between 2-23% of the cancers are
"insignificant" (too small) at the time of initial diagnosis. By that definition, the first
sprig of crabgrass or kudzu is "insignificant". Would you rather kill that first sprig...or
at least monitor the sprig... or later try to deal with it after it has spread larger or
taken over your yard? Monitoring implies things like watching the PSA velocity & other
facets of "watch & wait". Either approach may ultimately spare your yard of an
overwhelming infestation. There is yet no way to know in advance for absolute certainty
how big your cancer is. And we, and others, have shown that a big cancer can be in your
prostate gland when the biopsy series shows only a single tiny spot of cancer and/or when the
PSA is still in the normal range. Finally, the cancer treatments can potentially (not
necessarily definitely) lead to (variably manageable) problems with pain/irritation,
incontinence, and impotence...a potential negative which some would consider to be a small
price for the chance to gain control over a potentially life threatening disease. Others
prefer to watch & wait.
GET SCREENING TESTED WHILE YOU ARE
If a man has (by direct blood kin) a father, an
uncle, or a brother who has or had prostate cancer, screening should begin at an early age
(for example, age 30-40) with a combination of serum total PSA blood test (Prostate Specific Antigen (PSA)) and digital
rectal examination (DRE). In the absence of any such family history, at least the PSA blood
test should be utilized on a periodic basis beginning at 40 years in blacks and 50 years in
all others. Even if the PSA test result is normal (20% of cancer cases had a PSA less than
4), it is advisable for every man to also have a DRE by age 50. On the other hand, a high
percentage of elevated PSAs are not due to cancer...the PSA test, therefore, has a high
"false-positive" (for cancer)
rate. The transrectal ultrasound (TRUS) volume/size of the average normal prostate is
20 cc (20 grams...the size of a walnut); a gland is "enlarged" at 30 cc or larger. The PSA
level is somewhat related to gland size: 98% of men with a 25 gram (or smaller) prostate have
a PSA of 4 or less. If total serum PSA is greater than 10, the cancer likelihood is high
enough that many would advise biopsy on that PSA height basis alone.
A fairly small percentage of men run elevated
total PSA levels in the absence of biopsy procedures being able to find a cancer...sometimes
referred to as PSA "high rollers". This can be extremely frustrating to all concerned. One of
my physician friends is currently in this category. Another acquaintance ran a PSA in the
30's for years and had a biopsy series about every other year for maybe 8 years prior to
dying with pneumonia. These folks tend to have a stable level with very low PSA velocity. The
e-coil MRI (below) or
the more high resolution body-coil MRIs may help find the cancer; see "PSA parameters",
An example of a test "going by the wayside"
(what follows is a 1997 paragraph): I believed that the proprietary "ProstAsure
index" artificial neural network (ANN) test was an unknown/undisclosed manipulation of
the patient's age and several lab parameters (including serum total PSA) promoted with
misleading marketing brochures. And, because the marketing seemed dishonest to me, I didn't
trust the "test". I was disappointed that a renowned prostate surgeon lent his name to this
type of unethical marketing in the late 1990s. The test by Global Health Net, Savannah, Ga.,
does not seem to be available as of a check on it in early 2005.
WARNING!!! THE FIRST STEP...DIAGNOSIS... IS
If you are to have maximized ability to catch the
cancer early AND to weigh potential treatment choices, it is crucial to be biopsied well, to have the biopsies be
processed for maximum useful information, and to have the information made correctly available for staging
and treatment maneuvers. We believe that our pathology program meets these goals; and it was
available through all of the Columbia-area urology groups (until about 2006) and the
radiology group at Lexington Medical Center. In S. C. and across the nation as of early 2009,
most urology groups send the biopsies to owned labs elsewhere for financial advantages or
contracted labs to process & ship slides back to urologist offices & have a
pathologist not truly connected with the local medical community drive by and make diagnoses
in the urologist's office. Worse, a study published in 2011 among academic centers (not
point-of-service practices) documented a false-negative (missed seeing the cancer) rate of
1.7% and false positive (over-diagnosis of cancer when not cancer) rate of 0.5%. This
arrangement, while possibly being financially advantageous to the urology practice, detours
around a very important factor in behalf of the patient: Point of Service Pathology (the value of the diagnosis being made by
community pathologists credentialed on the local hospital medical staff & actually being
citizens of that community). With advance notice, we may be able to work with a urologist
elsewhere to use our system. And our duplicate diagnostic biopsy slides diagnosed locally can be
sent ahead for second-opinion evaluation should a patient elect treatment at a program anywhere
else in the world.
Findings justifying (or being indications
- if you have an
- if you have a PSA
velocity greater than 0.75 ng/mL/yr
- if your total serum
PSA is greater than 4 ng/mL (if you're 60 years old or older)
- if your total serum
PSA is greater than 3 ng/mL (if you're less than 60 years old)
Where indications reflect
that it is prudent to do so, prostate tissue biopsies are then undertaken. In patients at higher
risk for cancer, the above indications or "triggers" may be "pulled" at a lower
The previous general upper limit of normal had
been 4 ng/mL. But, in 2004, the NCCN lowered it to 2.5, especially for the mass screenings
that had become common. Many set "normal" with age-adjusted grades from less than 2 for men
younger than 41 and up to less than 4.5 at age 65. Should the screening PSA blood test be
abnormal, the patient could be knowledgeably examined with DRE and ultrasound (U/S). When
elevated, there are other parameters which can be considered.
- Serum free
vs. total PSA: In the elevated PSA range up to 20, the "free serum PSA" to "total (or
'bound') serum PSA" ratio may add some focus toward the likelihood of cancer or not. A ratio of
.24 or less (24% or less), especially .15 or less (15% or less), means a greater likelihood
that the total PSA elevation is due to cancer. As already noted above, the ratio of
"free PSA" and "bound PSA" (see above) may prove to be helpful tests, too. The
lower the percent "free PSA," the greater the likelihood of cancer...especially if lower than
15% (but, "silent" chronic periglandular prostatitis can also do this). So, a ratio target
below .2 (20%) or less may signal "do biopsies".
(PSAD): A clear elevation of the "PSA density" (when PSA is 10 or
less, PSA value divided by an estimate of the prostate gland volume/size below 0.15 is comforting,
0.15-0.18 is concerning, & 0.18 or higher warrants a biopsy)...this parameter is less
reliable [CAUTION!] with (1) very large glands whose size can "dilute out" the likelihood of biopsies finding
any of cancer (some now tackle this situation with "saturation biopsies"...as many as 20
biopsies taken from the gland at one surgical encounter, either transperineally or
transrectally) and (2) with obesity PSA hemodilution and (3) less PSA production per unit volume of cancer by black men (Kryvenko ON, et. al., AJCP, 144:271-7, Aug. 2015; same author later in 2015 in J. Urol.). This new view is PSA mass density (PSAMD). Only your urologist...who has knowledge of the size of your gland...is in the
position to follow PSA density. As of 2005, there is evidence that a man's PSA density (when
total PSA is 10 or less) above 0.18 means that there is a 24-fold greater chance that he has a
Gleason 7 or higher prostate cancer...a possible way to select only "bad [high risk] cancers"
for biopsy. But, use extra caution in (1) very large glands, (2) obese men , and (3) black men.
(PSAV): Prior to a decision to biopsy, the PSA blood test can be periodically
monitored (checking the "PSA velocity" &/or doubling time...the best way
to catch those hidden cancers with PSA in the normal range), possibly in conjunction with or
following an empirical course of antibiotic therapy (in case the elevated PSA is due to
infectious prostatitis). Your doctor can follow velocity (but so can you).
[on-line calculator at MSKCC link, below...upper right of page, click on
"prostate cancer prediction tool"; next page, at bottom of "disclaimer, click "I accept";
next page, scroll down to & click on "PSA doubling time" and then add in values &
dates for your series of PSA test results]. In 7/2004, a velocity of >.75 ng/mL/year was
an indication for biopsy when PSA is less than 4 and DRE exam "non-suspicious". By August
2007, the target suggesting "now do biopsies" has lowered to a rate 0.6 or greater for
time (PSADT): it takes about 35 years for a man with an ordinary gland to double his
PSA value; it takes about 20 years for a case of benign BPH to double. An average cancer case
caught early doubles every 4-5 years
A standard 1990s in-the-urologist's-office biopsy
protocol (begun in 1989) which was believed by many to give the highest chance of detecting
any prostate cancer which might be present is called the transrectal (biopsy device inserted
through the rectum..."up the butt") "sextant biopsy series"* (on each of the right and left
sides, a biopsy is taken of the apex, the mid portion and the base of the gland...six
separate biopsies in a pattern) performed with biopsy "guns" under U/S image guidance. The
patient begins to get prepared the day before. Each biopsy occurs with such mechanical
rapidity that a very high percentage of patients consider the procedure not objectionably
painful. So, anti-pain medicine is usually not used for 6 cores or less. Should the first set
of biopsies fail to detect cancer, one study shows an additional 30% discovery with a second
sextant series. By 2004, some had recommended repeat diagnostic attempts by the transperineal
"saturation" approach (see below). Depending on personal preference or specific situations in
an individual patient case (such as PSA 10 or less and/or a large gland...some would
recommend as many as 18 cores for a gland larger than 80 cc.), urologists may utilize a
different biopsy protocol*. Such additional protocols (additionally attempting to biopsy
midline, far-lateral, and/or transition zone areas of the gland) are said to have increased
the finding of cancer by 30% (by 2006, many of our urologists send 8-14 cores per case). In
the PSA range of 2-10, the Vienna nomogram came out in 2005 as
a means to help select the number of transrectal biopsies to obtain in a patient with
negative DRE & based on patient's age and gland size. Our radiologists began doing
temporary nerve blocks prior to biopsies on all of their cases in about March
Patient preparation consists of the
- completely emptying
the rectum with an enema (such as Fleets phospho) about an hour before the biopsies;
- starting an oral
antibiotic to begin the day before or no less than about 2 hours before the biopsies
When clinical suspicion or fear of malignancy is particularly high, a
"saturation biopsy" approach may be taken under sedation, or with local nerve block, or even
general anesthesia, performing 20-50 or more biopsies. We see up to 20 during office-based TRUS;
greater numbers are said to be done transperineally through the skin. Something akin to this has
been used in selection of cases for "focal cryoablation", see below.
Pathologist "reading" your
But, will the pathologist SEE the cancer? And,
will their lab operation assure that specimen mix-up does not happen. Our group experience is
based on processing a large volume of prostate biopsies (over 500 cases per year) since late
1990. It takes an expertly trained, sharp eye to notice the very tiny spots of cancer in
these tiny biopsy cores. Because it is a difficult task, not all of the pathologists in our
group were, early on, considered to have the particular personality type PLUS enough
experience to "read" prostate biopsies. The most likely danger is in failing to see the
cancer in a set of cores. And, it is not enough to just make the binary decision that a case
set of biopsies is either just positive or negative for cancer. The scrutiny must be so
concentrated and intense that each cancer spot which is present in any of the cores will be
found in all cancerous cores. If only some are found, the report could result in
under-staging. A lesser, but still real, problem is that of over-diagnosis of prostate
cancer. A third danger is that another patient's cancerous biopsies be mixed up and diagnosed
as YOUR biopsies. So, we recommend that biopsies be diagnosed by a pathology group with (1)
pathologists thoroughly embedded in the fabric of local community interests (not just as
employees of a commercial...usually distant...company; I recommend that your biopsies be read
by Point of Service Pathologists),
(2) external peer review (members of a hospital medical staff, for example), and (3) who
regularly deal in a large volume of prostate cases. Some groups with lesser volume and
experience protect against misdiagnosis by having all cases "read" by at least 2 pathologists
As already stated, the biopsy procedure and biopsy
specimen processing and interpretation are extremely important and represent the fundamental
foundation for all subsequent decisions. If the urologist is able to avoid tangentially
biopsying the gland (and is able to keep the exact biopsy sites well documented), and if
the blot-paper, agar-pre-embedding biopsy orientation technique is used
(currently , the only pathology group that I know of offering this process in the world is
Pathology Associates of Lexington, P. A.....see June 1996 issue Journal of the South Carolina Medical Association*), then
one has an optimal chance to actually find the cancer if it is in any biopsy cores. And, in the
cancerous cases, one has an excellent opportunity to get an idea of both the quantity and
spatial relationships of any diagnosed cancer as a basis to judge cancer size (a great advantage
when considering the W&W treatment option, below).
AND, having kept these small tissue biopsy specimen cores perfectly
oriented as to which end is deep and which is peripheral (toward the capsule), one might also
be able to estimate the closeness of the cancer to the prostatic capsule (we pathologists
must be very careful to microscopically confirm blot paper orientation of the cores...the
biopsy cores sometimes come out of the needle end-over-end onto the blot
I believe that the alternative core marking system
using dyes on the core ends is less dependable because the dye can mask subtle tissue
variations that could otherwise help one detect a miss-oriented biopsy core; and fragmented
cores can't be kept oriented.
Though these very small biopsy tissue cores allow
the pathologist to view only a very small amount of tissue under the microscope, we have
studied over 600 cases and found
that the cancer detection rate, surprisingly, is about the same as long as the aggregate
length of the series of cores on a case is greater than 2.6 cm. Yet we tend to agree with Dr.
Stamey that a sextant series is (we say "optimal"; Stamey says "adequate") most encouraging
to a search for cancer which seems negative when the cores add up to 5.0 cm. or more in total
The Gleason "grade" for primary treatment
decision making is interpreted from the biopsies, see below.*
Biopsy problems with
In about 5% of cases in which the biopsy set is
not clearly benign, one will find a microscopic cluster of "suspicious
glands"...ASAP (atypical small acinar proliferations). About 75% of that 5%
can be clarified in-house (in our lab) by using the IHC stain for 34BE12 (keratin 903...K903
or k903) on the biopsy slide. About 10% of that 5% group...after collaboration by two or more
of our pathologists...are felt likely to be definitively diagnosable by an acknowledged
world-class expert in order to be more sure of a particularly difficult diagnosis; and
sometimes we seek that expert opinion right away...other times we await the direction of your
urologist or treating or biopsying doctor. Rarely, even the expert remains uncertain of the
correct diagnosis, and re-biopsy is possibly necessary. It usually takes such an expert
consult less than a week to FAX an answer to us. The other 15% of that 5% group remain in the
ASAP category which must then be followed in a variety of ways by those patients' urologists.
Re-biopsy may eventuate, sometimes following attempts to "see" the hidden/occult cancer (if a
cancer truly be present) with e-coil MRI. Various studies
show that from 21-49% of re-biopsied ASAP cases result in a cancer
CRUCIAL POINT: Patience
You MUST BE PATIENT! Accuracy of diagnoses and
special studies depend on tedious, methodical efforts; high-pressure pressing for information
runs the risk of increasing the chance for error. An analogy: you can't force a gallon of
water through a common drinking straw in less than a minute without serious risk of rupturing
##########Now, How Bad Is
SO, WHAT NOW?
Having now diagnosed prostate cancer, a great deal
of effort and physician contemplation is now to be directed toward determining whether the
cancer is "CLINICALLY SIGNIFICANT" (dangerous in view of your likely future lifespan) versus
"NOT CLINICALLY SIGNIFICANT". The Humphrey Formula attempts to alert
that a cancer is not likely "clinically insignificant". The Kattan nomogram ( one discussion, HERE) attempts to predict the likelihood that a cancer is indolent
and non-aggressive (the kind that one might "watch & wait" as to deciding treatment). A
"basic" and an "enhanced" calculator of the Kattan nomogram is an online MSKCC nomogram that calculates likelihood of indolent cancer (our graphic shows the 1992 TNM stage criteria
[the 1997 criteria only two T2 choices, T2a...one lobe/gland-half involved...and T2b, both
lobes/halves with cancer]) & some other risk data.
How bad is your
recommendations/decisions rest on three broad parameters:
- the patient's
general health status: the healthy do better than less
- a best estimate of
the cancer stage and grade: low stage/low grade does better than high stage/high
grade...and, along these lines, whether the cancer is compact (and can be "shot" with an
expertly aimed rifle bullet) or is poorly compact (clues = Gleason 4 or 5 component, perineural
space invasion, or capsule penetration seen on biopsy or e-coil MRI). Poorly compacted is more
likely to be fired on with a "shotgun blast" or "carpet bombing".
- the patient's
age: younger tend to be healthier & do better than
The above three are rules
of thumb. Don't be insulted or feel discriminated against...these are generalities. You may be able
to provide valuable decision making input to your doctor. If you haven't already...or maybe you
want to restate it, then you might be sure to speak up about your philosophy or inclinations (what
you fear the most...be brutally honest with your doctor) toward treatment and other decisions. The
following staging and grading procedures are considered in addition to an individual patient's
particular desires and in consideration of likely remaining life span (had there not been any
diagnosis of cancer).
By way of the height of elevation of PSA levels*;
by bone scans*; by ultrasound (U/S) examination*; and by DRE*, the majority of staging (how
big is it and how far has it spread?) information is gained. Rule of thumb: "curative"
treatment is attempted with cancers believed to be confined (or confinable) to the prostate
gland. Note this 1992-criteria staging graphic.
levels: the higher the PSA, the more likely cancer has spread out of the
scan: prostate cancer strongly tends to go to the bones; a positive scan (there are
many false positive cases) could mean cancer has gone to the
positivity: an insensitive, but sometimes positive method to show cancer escape from
- endo-rectal-coil MRI positivity: a parameter that can pick
up extra-capsular extension. Other precise imaging exams are coming onto the scene (the point is to get a high quality view of the capsular boundary).
positivity: an insensitive, but sometimes-positive method to feel both cancer size and
escape from the gland.
Also, our unique biopsy
processing potentially allows specific interpretation as to the relationship of the cancer to the
prostate capsule. And it also allows estimates of quantity of cancer (the more the cancer,
the greater the likelihood it has gotten out of the gland) AND percentages of the Gleason grade
patterns (that is, patterns 3, 4, or 5).
MRI: In addition, to maximally
avoid under-staging (erroneously thinking we're dealing with a "better" situation when such
is not correct), the endo-rectal-coil Magnetic Resonance Imaging (e-coil MRI)* can be
utilized and has been part of our hospital's diagnostic array since October 1995 (by 2009, we
use a high resolution body-coil MRI in those who are not too obese in order to avoid the
discomfort of the endorectal device). In addition, the body-coil MRI* (previously being the
ordinary resolution & now the high resolution MRI) is employed to check the pelvic lymph
nodes status. In our program, the prostate biopsy findings are uniquely and carefully
correlated by a graphic (graphic
report example) provided by us to the diagnostic radiologist for maximum interpretation
of the e-Coil MRI images. We have been enhancing this MRI accuracy as of 1 Jan. 1999 through
the addition of the "phased-array coil". This allows "dual acquisition" of computerized
images by the endorectal probe and an external, small acquisition apron placed on the lower
abdomen...such dual input is able to eliminate a great amount of "imaging noise" and produce
images with much sharper contrast. The combination of fully-oriented biopsy interpretation
and e-coil MRI correlated interpretation allows the greatest opportunity to optimize
pre-treatment planning: information is gained as to tumor size, exact tumor location, the
relationship of the tumor to the capsule, the relationship of the tumor to neurovascular
bundles; and all of this allows for a more precise interpretation of stage (a graphic demonstrating the TNM staging
system) (from Harvard Med. School and Hosp. of the U. of Penn..."Endorectal Coil MRI..."
Urology vol. 51, #3, pages 449-454, in 1998).
Dual acquisition e-coil MRI is helpful in
4 patient situations:
- When doctor desiring to locate a likely target
for biopsy in PSA "high rollers" (see "screening", above).
- Those who appear to have small cancers (by
biopsy findings and normal-range or only mild elevations of PSA) without "significant"
Gleason 4 or 5 component, in whom radical surgery (or even "watch & wait") is desired
but want extra assurance that cancer has not penetrated the prostate capsule...has not
already progressed to level T3 disease.
- Those who seem, on the basis of a lot of
biopsy positivity for cancer, to have a lot of cancer (large cancer size) but without
high PSA levels, without significant Gleason 4 or 5 component, and who desire radical
surgery or closely focused radiation therapy (seeds, 3DCRT, IMRT, IGRT) but want extra
assurance that cancer has not penetrated the prostate capsule...has not already
progressed to level T3 disease; and,
- those incidentally found to have "a little bit
of cancer" in their TURP specimen (to help give an idea of the extent of cancer in the
gland as an alternate to biopsies; TURP removes tissue in the center of the gland and
toward the base...cancer usually in gland periphery).
Yet, even as of July 1999 *(still, in 2007, I
think our program is the only one in S. C....certainly central S. C....using this), there
continues to be a strong impression among many of our area urologists that e-coil MRI "is not
that good"..."you don't hear anything mentioned about it in state, regional, or national
continuing education meetings."
Additionally, where radical prostatectomy is
contemplated and node sampling may be required, laparoscopic* pelvic lymph node biopsies may
be obtained prior to any major surgery (we don't see this done anymore as of about 2003); or,
the nodes can be tested during surgery by frozen section (we commonly participated in this
but not frequently since late 2005) exam * or as part of the ordinary postoperative pathology
staging exam done on all removed tissue.
studies...radioimmunoscintigraphy... in nuclear medicine are a newly approved (about 2002)
way to pre-operatively look for lymph node or bone metastases: an antibody is locked to a
radioactive tracer, and the antibody attaches most avidly only to prostate cancer cells. The
aggregated attached molecules then "light up" any PSA-positive cells so that the nuclear
medicine camera can "see" it. It is said to be 15 fold better than CT scans and 5 times
better than body-coil MRI scans in detecting lymph node metastases and exact recurrence
locations...and may find a metastasis even when serum PSA not elevated. It is a test with a
considerable false negative rate but low false positive rate. We have even picked up an
unexpected isolated skull metastasis in one case in late 2004.
PET Scanner* studies use an F18 radioactive
glucose injection, "FDG", to locate "hypermetabolic" tissue...such found areas almost always
being cancer (for example, finding cancerous lymph nodes)( very expensive instrument and
support personnel; available in relatively few cities). At Lexington as of Sept. 2002; full
PET scanner here as of 2003.
"Coincidental" Scanner** studies use a much less
expensive arrangement to perform...using the same isotope...almost the same search that the
PET Scanner performs, but with a little less detection ability. As a "poor-man's PET
scanner," this test is available in many more locations.
The above measures are often not warranted. New technology is always coming onto the scene. In
some situations, some additional diagnostic determinations are used in trying to factor in
some risk information relative to the likelihood that pre-treatment staging might not be
"what it seems": additional tumor characterizations may be performed on the cancer in the
biopsy specimens, as follows:
CANCER GRADE: HOW BAD, HOW VICIOUS, AN
ACTOR IS YOUR CANCER?
But, the additional key question revolves around
whether it is a "better" or "worse" (meaner) cancer...the GRADE of the cancer (remember,
"grade" is determined by the pathologist). If the tests on the biopsy suggest a "worse"
cancer, this can influence a change in treatment choice. If the biopsy shows a "better"
cancer, then we continuously know and keep in mind that there still could be
undiscovered/undisclosed "worse" cancer in the untested areas of the gland (the gland still
being in you). Grading is according to the Gleason system.
Gleason (sum) score:
Gleason reporting details:
Latest prostate pathology textbooks suggest the
following reporting rules, to include separate scores for each separately labeled biopsy core
having any cancer:
- if only one pattern, report
such as 3 + 3 =6.
- if two patterns, at
least report perceived dominant first and minority one second (we try to estimate percentages
& it is VERY valuable in cases with a score of 7, such as:
4 (60%) + 3 (40%) = 7.
- if 3
in biopsies: sum the dominant plus the highest grade
pattern of the next two (even if highest is quantitative minority), such as: 3 (50%) + 5
(4%) + 4 (46%) = 8.
in radical prostatectomy: only requires summing the two
most prevalent patterns...but one should mention any 3rd (minority) 5 pattern because higher
PSA failure rate.
One way to try to grasp the concept of "grade"
expressed as a Gleason "sum" or "score" is to think of dogs and wild wolves. A domestic, nice
lap dog usually doesn't bite...it may bark a lot and be scary. It's bites could hurt, and
rarely there is a death due to such dogs [these are like "sum" 2 thru 5, well
differentiated]. If at least trained and controlled, larger, common pet dogs seldom kill but
do so more than the lap dogs [these are like the "sum" 6, moderately differentiated]. "Sum" 7
is more like a German Shepherd, Rottweiler, or pit-bull, capable of killing...it is just hard
to know which are "nice" and which are killers. "Sum" 8 thru 10 are like a pack of hungry,
wild wolves, and you are alone at the camp site. You are in need of weapons, and you need
them now !!!
Note the % dead in 15 years IF NO TREATMENT at
1. Gleason score (sum) 2
thru 4,.... 4-7% dead in 15 years
2. Gleason score
5,............ 6-11% dead in 15 years
3. Gleason score
6,............18-30% dead in 15 years
4. Gleason score 7 (but 4
+ 3 = 7 is worse than 3 + 4 = 7),............ 42-79% dead in 15 years.
5. Gleason score 8 thru
10,... 60-87% dead in 15 years
Has the "horse" gotten out of the barn
What is the probability, by Gleason score
alone, that the cancer is still locked inside the prostate gland? If biopsies
1. Gleason score 2 thru
4,......... 74% probable that it's "locked" in the prostate.
2. Gleason score
5,................. 58% probable that it's locked in the prostate.
3. Gleason score
6,................. 53% probable that it's locked in the prostate.
4. Gleason score
7,................. 29% probable that it's locked in the prostate...(but 4 + 3 = 7 is worse
than 3 + 4 = 7).
5. Gleason score 8 thru
10,........ only 17% probable that it's locked in the prostate.
What if you consider Gleason plus other
You can take your Gleason score, PSA value, and
the stage assigned so far by your urologist and see a more specific probability rating of (1)
still locked in the gland, vs. (2) probably out of the gland, vs. (3) probably gone to lymph
nodes by going to the Partin Tables (nomogram) in the Johns Hopkins web site. Or with biopsy
pathology report alone (if it contains sufficient detail), you can use the Hamburg algorithm to see your risk that cancer has gone to the pelvic
What about proportion of Gleason 4 & 5
Dr. Stamey, as have others, showed in 1999 (JAMA
281:1395-1400, April 21, 1999) that the percentage of any Gleason 4 or 5 component and cancer
volume/size are the strongest predictors of disease progression. He translated the study to
give meaning to the Gleason grade within an ADEQUATE (sextant or more, aggregate biopsy
length of 5.0 or greater centimeters...2 inches) set of biopsies, as
cancer: If the biopsy-revealed that cancer had 20% or more Gleason 4 or 5 component,
then the gland remaining in you has about a 90% certainty of also containing this much "bad"
component and, therefore, has a significantly increased surgical treatment failure-to-cure
rate. This strongly suggests an increased failure likelihood for other types of closely focused
treatments (low-penetration seeds, too tightly focused 3dCRT, IMRT...even if image guided IGRT,
nerve-sparing radical surgery, PBT, or too conservative cryosurgery). And these cases are not
candidates for "watch and wait" unless there are compelling reasons to very carefully do so.
Some will use the above in such cases and concomitantly cover with androgen deprivation
cancer: If biopsies have no 4 or 5 component, then there is 90% certainty that the
gland remaining in you has no "bad" component and, such patients might expect only a 5.6%
likelihood of treatment failure.
cancer: If biopsies have some Gleason 4 or 5 component, but less than 20%, it is a
While Gleason percentages seem to be a powerful bit of information, your doctor must specifically
consider all other of YOUR factors!
Gleason score has an influence on choice and
intensity of treatments. As some rough and quickly potentially obsolete
1. Gleason score 2
thru 6: might choose "watch and wait", or ordinary external radiation dose, or
radical prostatectomy , or radiation seeds, or treatments relying on high probability the
cancer is still locked in the gland. Will probably not need added hormone suppression. So,
the pathologist must be careful to not undergrade the Gleason score. Gleason 6 or less often
best candidates for "focused" treatment...shoot it with a rifle.
2. Gleason score
7: might choose ordinary external radiation dose, or radical prostatectomy , or
radiation seeds, or treatments relying on high probability the cancer is still locked in the
gland. Hormone suppression therapy possibly needed. It is so important that the pathologist
detect ANY Gleason 4 or 5 component, because that information will likely cause your doctor
to add on hormone suppression (giving a 50% increase in survival advantage) and be a factor
against using just seeds or other intensely focused treatments.
3. Gleason score 8
thru 10: will likely choose "shot gun" or "carpet bombing" approach of increased
external radiation dose, or possible radical (debulking) prostatectomy , or probably not radiation seeds
or treatments relying on high probability the cancer is still locked in the gland. Hormone
suppression therapy probable.
The Gleason grade is assigned by a pathologist*
looking at the biopsies under a microscope; and it is a numerical assignment of the cancer
pattern scores, it usually being expressed as numbers (such as, 3 + 3 = 6). Pattern scores
range from 1 to 5, and the major (the greatest quantity) pattern plus the minor (the lesser
quantity) pattern are added up to calculate the grade "sum". A grade "sum" of 5 or lower is
"better"; a 7 or higher is "worse". A 6 is "average". The American Joint Committee for Cancer
Staging, 5th Ed.: "sum" 2 thru 5 is "well differentiated"; 5 thru 6 is "moderately
differentiated"; 7 is "moderate to poorly differentiated"; and 8 thru 10 is "poorly
differentiated". Some consider any major or minor pattern score component of 4 or 5 as being
worse. Therefore, you might occasionally see a cancer scored, as an example, 3 (60%) +5 (5%)
+4 (35%)+=8...in order to let your doctors know that there is also a little bit of Gleason 5
pattern in the cancer. Studies have shown that, left entirely untreated, the following are
the percentages (also see above) of survivors at 15 years after diagnosis (but keep in mind
that scores on biopsies may under-represent the score of what remains in the gland, see
below): Gleason scores 2 thru 4, 93-97%; Gleason score 5, 89-94%; Gleason score 6, 70-82%;
Gleason score 7, 30-58%; and Gleason score 8-10, 13-40%.
Former Mayo Clinic pathologist, Dr. David
Bostwick, reported long ago a tendency for pathologists to under-grade (diagnose it
"better" than it actually is) the Gleason score (Am. J. Surg. Path. 22:1169-1170, 1998). I
feel that under-grading is more likely from pathologists seeing an insufficient volume of
prostate cases and/or lacking a primary interest in prostate cancer. Our group has
standardized our scores...and guarded against undergrading...by way of training time one of
our group spent with Dr. Gleason plus tutorial time another of our group spent one-on-one
with Dr. John McNeil at Stanford: these experiences are integrated into the practice of our
group. The group then underwent comparison grading on numerous cancer cases. Yet the toughest place for consistency is
between a pattern 3 & 4...which makes the difference between a score of 6-8. I think it wise
to let the report express any reservation about choosing an interpretation of Gleason 6 rather
than 7. We always assign a Gleason score to your cancer. The higher the score, the more likely
the cancer is out of the gland.
"For profit" Commercial Labs and
I don't believe that the Wall-Street-owned or
privately owned commercial or entrepreneurial labs & their employee pathologists are
sufficiently grounded in a local community of referral doctors (or bonded in local citizenry
with the local population) to have the kind of "point-of-service" attitude & concern
that is in the best interest of patients...particularly on (1) some of these critical Gleason
determinations and (2) the finding of small quantities of cancer in the biopsies. You can
always request (just call the diagnosing lab and make an official request...or have your
urologist's office do it) that any lab obtain a second opinion on your case. We would be
happy to give second opinions [how to]; or, you can
have them obtained from expert uropathologists in centers such as Johns Hopkins, Mayo
Clinic, Cleveland Clinic, Stanford, and others. Studies attempting to portray reliability of
commercial diagnostic lab assignment of Gleason scores by comparing biopsy scores with scores
found in radical prostatectomy specimens are of limited value (but, Dr. Stamey's, above, is
valuable) because they do not account for all of the cancer cases not resulting in radical
prostatectomy. I believe that for-profit commercial labs who use this type of deceptive and
misleading advertising are using unethical and deliberately-misleading
The second biopsy determination...we always check
for this... is a search for PSI: the presence of cancer in microscopic spaces around
prostatic nerves ("perineural space invasion"...PSI..."PNS positive").* Some 85% of cancer
penetrations out through the prostate gland capsule happen along-side of the nerves coming
into the gland (highest concentrations at apex and base as the neurovascular bundle runs
along each posterolateral side of the gland). "Positivity" near the capsule ups the odds that
tumor has invaded through the gland capsule, whether it can be specifically visualized or
not. And its presence may strongly influence treatment choices, it being a soft clue to that
particular cancer's ability to scatter beyond local lines of resistance. Treatment choices
which are focused (nerve-sparing radical, low-penetration seeds, PBT, cryo., 3D-CRT/IMRT and
IGRT tightly focused around the gland) may be more risky in the face of positive PSI (see
treatment details, below). Positive PSI on a biopsy has a positive predictive value of 93%
that the capsule is at least microscopically penetrated (of 100 cases having a biopsy showing
PSI, 93 will have capsular penetration documentable in the radical prostatectomy specimen).
Biopsies showing PNS (perineural space) negativity are no guarantee, however, against capsule
The Gleason grading system subjectively recognizes
5 cancer "patterns" in any positive biopsy core. And, it adjusts for the common fact that
prostate cancer most often contains two patterns by creating a Gleason score consisting of
the sum of the estimated percentages of the majority pattern plus the minority pattern, such
as 3 (60%) + 4 (40%) = 7 (see more, below). Otherwise, it contains one pattern, such as 3 + 3
= 6. Rarely, the samples show 3 patterns.
Proliferation Rate (how fast it is
Ki67 proliferation marker: this third biopsy
determination can be an added double-check on the Gleason score. This is an
immunohistochemical (IHC) marker stain which can be applied to the malignant biopsy if there
is debate as to the correct Gleason score...especially as to whether there actually is
significant 4 component. There must be a minimum of 500 stainable cancer cells. If greater
than 7.5% of the cancer nuclei are positive, a study elsewhere of almost 100 patients showed
that their tumors behaved aggressively (like Gleason 8-10). Immediately after the published
study of 8/98, we used this test on a case of 4(70%) + 3(30%)=7 in order to see if we should
better just interpret the case as an 8. We have seldom seen the need to perform this test .
However, in late 2003, a report came out to the effect that increased rates of treatment
failure happen when the rate of Ki67 positive nuclei is 7.1% or higher.
The fourth biopsy determination is "DNA
ploidy"***: a determination of "diploid" is "better"; any other determination may be "worse";
ploidy has to do with chromosome status. Many consider that the DNA ploidy is just another
way of reflecting the Gleason score and is not an independent signal of "better" or "worse".
DNA ploidy can be very difficult
to determine accurately on tiny spots of cancer within these hair-like biopsy cores (and
may...no one is certain...only be of use when treatment is non-surgical). We have only rarely
attempted this test; and we can only currently attempt a determination on RE-BIOPSY specimens
solely used for DNA analysis. (We are almost never involved in such DNA
P27 proliferation "brake"
Another marker coming out in late 1998 is for
P27...said to be a cell protein which modifies the rate of cell proliferation...holding
proliferation somewhat in check. Initial work suggests that tumors low on P27...having "weak
brakes"...grow and spread faster and easier than tumors with adequate levels. This is
determined on biopsies (we have never had a request for this test as of Sept.
I was disappointed that the American Cancer
Society, about 3/96, reported this test to the media as if it were the greatest break-through
ever. We have significant doubts that this blood test can play any reliable role in
pretreatment staging estimates because the technique detects and amplifies extremely minute
quantities of PSA protein antigen. The idea was that, if the test was "positive", cancer had
already gotten into the bloodstream. The significance of such is totally unknown because it
could be that this cancer antigen is periodically shed into the blood by cancer still
restricted to the gland.
Summarize Your Cancer Riskiness
situation: (a) good life expectancy otherwise, (b) Gleason score/sum 6 or less, (c) PSA 10 or
less; and (d) staging T1c (positive biopsy & negative DRE) to T2A (palpable...positive
DRE...& in half a lobe or less)...no evidence of node or distant metastasis (the above
affirmed May 2007 AUA...J. Urol. 177:2106-2131). I would personally also want to have the
e-coil MRI to be sure no
obvious capsule invasion or malignant component that is MRI-visible but not producing its share
of PSA. In "favorable", all treatment options are in play, including expectant management
if: (1) patient can stand the idea & (2) small lesion...no worse than T1c (controversial if
younger than 60)...(best if evidence =/<0.5cc of cancer, something like cancer in 2 or fewer
cores of at least 12 cores [unless gland not large enough for 12 biopsies] and no core more
than 50% cancer...PSA density =/< 0.15ng/ml/cc). There has been a series of research studies attempting to find other concretely objective analyses that can confirmatorily suppliment the above favorable parameters [check highly technical examples HERE].
- intermediate/uncertain: good life expectancy otherwise; Gleason score/sum 7;
PSA 10-19; and staging T2B/T2C.
- poor/worse/high-risk: good life expectancy otherwise; Gleason score/sum 8-10;
PSA 20 or more; and staging T3 or worse. Yet, a small percentage of cases move incredibly quickly, as apparently was the case for a pathologist who inspired me early in my career, Doug Shanklin.
Your doctors try to categorize your cancer
situation as "better", "worse", or "uncertain" in order to plan your treatment and
HOW LONG WILL I
No one can truly tell you how much time you have
left; if pushed by patients or family, many doctors provide educated guesses. Remember, you
could live to age 100; or, you could die in a wreck next week...with or without
Statistics speak for a large group...you are singular/unique! So,
statistics are only a guess for you:
It is vitally important for the patient to
understand that published statistics as to various treatments only represent a source of
IMPERFECT, after-the-fact, possibly-seriously-outdated information. And that his own case is
not, itself, part of some statistical analysis. You, the patient, represent a statistical
universe of only one case! Therefore, a tremendous amount of the patient's contribution to
treatment decisions and his ultimate satisfaction rests with his own understanding of what he
fears the most (cancer, surgery, radiation, chemo, "not knowing") and what he suspects he can
best tolerate. Remember, he is now facing "dealing with" cancer for the rest of his life. How
can you rest easiest while dealing with it? Take the factor of impotence: taking away any
treatment or proposed treatment, even taking away the fact of cancer, this dysfunction is
extremely related to both mental and blood vessel factors, anyway. In short, don't get "hung
up" on statistical figures much beyond "unlikely", "occurs commonly", and "very likely to
occur". Besides, complications, such as impotence, can take on a totally different meaning
with drugs like Viagra appearing on the market.
Doctors must consider the ENTIRE
Treatments are selected or advised according to an
overall analysis of the patient and situation, a key bit of info being hard for us
pathologists to know is (1) such as the Charlson co-morbidity index (CCI)...what kind of
medical "shape" you are in... to help in treatment choices. Then there is a careful analysis of (2) the PROBABLE
stage (how big and how far the cancer has spread) and (3) Gleason grade of the cancer. A
treatment strategy may be "for cure"; if the cancer stage is too high, a treatment strategy may
be designed "for palliation" (making the best out of a probably fatal situation). In between is
a large group treated for "control" of the cancer...to delay progression of a
probably-not-fully-curable cancer. Also, one might elect at first to just "control" a cancer for
a year or two in order to evaluate treatment options at a later date, potentially taking
advantage of future newly approved treatments. Part of a treatment strategy may be directed
toward local control or elimination of cancer; another part of the strategy may be for systemic
(body-wide) control or elimination of any known or suspected cancer. Finally, one must carefully
consider an initial treatment choice, keeping in mind what possible secondary treatments might
be available later should the first treatment strategy fail. Following is an incomplete list of
initial treatment choices.
Many patients become decision-paralyzed with
information gathering and information overload that still leaves them in this gray zone of
indecision...it just won't come up black or white! And they fervently desire that an expert
were to appear who will say, "We have thoroughly analyzed your case, and there is no question
that there is one and only one best treatment for you." Almost always, there is more than one
choice: remember, specialists tend to be honestly biased and more confident toward that which
they do best. So, you will probably never be a satisfied patient until you accept
responsibility for being a full partner in making the choice. Also, remember that you, too,
have a prejudiced mind-set (some minds are set against or in favor of certain kinds of
treatment just as some gardeners believe in pesticides and some in natural pest control, some
in digging weeds...to include all of the roots...out, and some in using
FIVE INTERNET SOURCES POSSIBLY HELPING TO
ORGANIZE YOUR THINKING TOWARD DECISIONS...COMPUTER DECISION AIDS:
- Prostate Cancer
Profiler is/was a site you can register in and plug in
your case information and try out some treatment scenarios (can do this for bladder,
breast, colonic, prostate, and melanoma skin cancers)
- Prostate Cancer Research
Institute (PCRI) is a site with lots of decision
aids (many on-line nomograms) and educational material...especially pre-treatment
decisions such as to "active surveillance" of "low-risk" cancers.
- CHESS Prostate Cancer
Module of the U. of Vermont Medical Center,
Fletcher Allen Health Care System.
- National Comprehensive
Cancer Network is an informational site which
includes decision trees as a decision-making tool. On the home page, point to the
"patients" area near top & note the drop-down list & click on "patient
guidelines". It will take you to a new page; scroll down to near the bottom and "click"
on Prostate Cancer. This takes you to a page with a menu on the left (or, you can scroll
to the bottom and select from a different menu...same topics). Select and "click" on
- Memorial Sloan Kettering
Cancer Center (MSKCC): Check "nomogram"...pick
prostate. There is a pre-treatment tool to help decide among the choices for treatment
options; other nomograms help decide prognosis. Others help you insert your PSA levels
and testing dates to check the PSA velocity and doubling
LIST, PRIMARY DISEASE:
***One source's website thumbnail overview of the common
treatment options, HERE.
- Watch and
wait:* Also called "watchful waiting", "active surveillance", "proactive monitoring",
"expectant management", or "expectant management with curative intent"; PSA checks (PSA velocity) plus close
urologist follow-up by way of DRE and U/S (maybe annual
- Surgery:* open, manual or robotic laparoscopic, radical
removal with bilateral nerve sparing.
- Surgery:* open, manual or robotic laparoscopic radical
removal with one-sided nerve sparing.
- Surgery:* open, manual or robotic laparoscopic radical
removal without nerve sparing.
- Radiation:** open-abdomen, operative (retropubic free-hand)
radiation seed implant brachytherapy (now probably considered old-fashioned).
- Radiation:** U/S-guided radiation seed implant [permanent]
brachytherapy: high penetration isotope (e.g., gold).
- Radiation:* U/S-guided radiation seed implant [permanent]
brachytherapy: low penetration isotope (e.g., iodine or palladium).
- Radiation:** U/S-guided high-dose-rate (HDR) [temporary]
brachytherapy (hot "seeds" via catheters).
- Radiation:* External beam radiation (2-D) therapy (XRT).
With or without initial 3-D field planning (3DCRT), (with**) or without IMRT (3DCRT plus
modulating...varying...the dosage, depending on tumor shape variations in your tumor), with or
without IGRT (IMRT plus a CT recheck of tumor shape & position at each radiation
- Radiation:** Intensity modulated radiation therapy
(IMRT)...closely arranges radiation to prostate & relatively spares the surrounding tissue.
But, structures move (for example, during breathing). If so in your case, respiratory gating
may be used. And image guided techniques at each radiation session may be used with the IMRT
- Radiation: Cyberknife (highly focused robotically aimed
external radiation with gating...sometimes called "radiosurgery)...has advantages over the
Gammaknife. Not any surgery at all.
- Radiation:** Proton Beam Therapy (PBT).
- Medical:* combined hormonal deprivation (CHD), sometimes
known as "total androgen blockade".
- Freezing:* ultrasound guided cryosurgery, both as to total
gland cryoablation or as focal cryoablation.
- HFU: High frequency ultrasound (street lingo = "high
a. Pre-radical-surgery neoadjuvant
b. Combination seeds and
c. Other sorts of
combination sequences or salvage procedures.*,**
c. Spot XRT to bone
d. Vaccine therapy (Johns Hopkins
e. Anti-proliferation therapy with
calcitrol: alone or in combination with CHD, this anti-proliferation drug has been used
to slow the growth of tumor...a delay-progression tactic.
f. Chemotherapy*. even though it's
not standard procedure, a piece of metastatic cancer...if it can be surgically
obtained...can be forwarded to a laboratory (Oncotech) for extreme drug resistance
testing (EDR) so as to avoid toxic chemotherapy that would have a high percentage chance
of not working. Our lab participated with Oncotech until about 1999... but almost never
as to prostate cancer.
g. Super-radical salvage surgery
such as total pelvic exenteration (very rarely chosen).** or maybe salvage
Good layman articles about how they made their
choices in May 13, 1996 issue of Fortune magazine.
Some Rules of Thumb About Each
- Watch and
wait (W&W): This "active surveillance" or "expectant management with curative
intent" is the only "treatment" which is entirely free of treatment-induced side effects. You
must be the type of patient who is totally reliable about playing by the rules. Only if the
Gleason score is "better" and if all staging criteria otherwise strongly suggests a small,
prostate-gland-confined cancer (a favorable case). Especially
if you are old enough or have other serious health issues making it unlikely that you have more
than 5-10 years to live, otherwise...AND, if you can tolerate knowing that the cancer resides
in you...this could be your choice. All other treatment options continue to remain available at
all times while you do "W&W". Dr. Gleason (JAMA 280:1034, 9/98) reports that...based on a
study of 767 men; those with a score of 7 to 10 have a high risk of death from the cancer;
those with score 5 or 6, have a more modest risk. While you "watch and wait", you have time to
"educate" yourself about future game plans. Your risk lies in the imperfection of our ability
to be perfectly sure of your cancer stage and "better" versus "worse" Gleason grade and case
type/status. W&W is an approach more likely for those aged 75 or older (BUT, some
[see PCRI] are working this with much younger, highly motivated men). Or
it can work for those who strongly want to avoid treatments and in whom it is estimated that
the cancer is no larger than 0.5 cc. and PSA doubling time is known to be higher than 3
years. In one of our nation's most prestigious medical journals is this case diagnosed at
age 55 & dramatically cancelled surgery & then re-evaluated & staying with
W&W at age 65...all issues discussed...see if your hospital or local public library can
get a copy for you if REALLY interested in W&W [reference]. AND, as mentioned above, parameters indicating W&W as favorable are less dependable in the obese patient anbd the black patient, ABOVE.
As sort of a double-check on your decision to W&W (especially if your cancer has any
Gleason 4 or 5 component), you might consider monthly to quarterly PSA tests, beginning 3
months after biopsy, during the first decision year: if PSA is stable or barely increasing,
this suggests a safe decision. If it is increasing, try to figure how long it would take to
double at the present rate [a PSA doubling time is actually usually a logarithmic rate...the
PSAdt]. If it looks like it might take only as little as 18-24 months for your PSA to double,
then you are in danger of cancer progression in as little as one year. If it looks like the
PSAdt is greater than 3 years, then there is a suggestion that the cancer won't progress for
more than 3 years [the report on this...Cancer, 1998, 82:342-348... checked on 113 men with
starting PSA of 21 or less].
A December 2004 report (J. Urology, vol. 172,
p.2193-96) suggests W&W is reasonable for men with "favorable" cancers of "small
volume". Favorable is: PSA less than 10, clinical stage no worse than T2a, and Gleason
score no worse than 3 + 3 = 6. Small volume is: T1c, PSA density of 0.15 ng/ml/cm3 or
less, and cancer in only 2 or fewer cores and never more than 50% of any positive core. A
majority (93%) of the men who fit the W&W criteria in this report were able to just
W&W. The W&W program [active surveillance] at Johns Hopkins indicates a belief that at least 80% of
men who fit this small volume data set actually have small volume cancer; and they confirm
the above with at least a 12-core-biopsy pattern, if gland large enough. Annual
biopsies are part of that program...part of the parameters that are "watched" to detect
progression. If progression (JHU = more than 2 positive cores or >50% of core cancer, or
Gleason changes to 7 or higher or unusual rate of increase in PSA),
then treat with curative intent. Known to me is a Gleason 3+3+ 6 by biopsies ended up with a metastatic iliac node (CN16-3)...so, as with any issue, there is real adverse risk!
- Radical Surgery: This is a
classical "go for the cure" strategy for those desiring to wage their fight with surgery.
Best candidates are typically 60 years old or younger. If there has been previous disease
scarring or pelvic injury affecting tissues near or about the prostate, any surgery may
be fraught with elevated risk of complications. Also, odds are best with those cases
showing evidence that the cancer is confined to the prostate gland (lower elevations of
PSA, biopsy findings negative for risk markers of extra-glandular spread [cancer in the
capsule boundary and/or perineural lymphatic positivity, DRE or e-coil MRI or MRS
indication of extra-glandular extension, and a Gleason "sum" or score containing any
significant amount of 4 or 5 component]). Magnetic resonance spectroscopy (MRS...MR spec)
is becoming available in some places (as of 2006) to help double-check size and location
of the cancer (potentially allowing focused...IMRT/IGRT...radiation "boosts" to the
localized area)...MRS is in our area as of 2007.
As of early 2005, open suprapubic (going in
above your pubic hair line) radical prostatectomy (OSRP [radical retropubic
prostatectomy...RRP]) is the standard most urologists perform...done extra-peritoneally.
Simply because training programs teach it far less frequently, transperineal (going in
through your bottom between the scrotum and anus) is an option. Transperineal
prostatectomy has poorer (no?) access to lymph nodes & should be done by a urologist
with regular experience with this approach. The first laparoscopic (avoiding opening the
abdomen) prostatectomy in S. C. [S-05-1406] was performed at our hospital. Air is put
into the abdominal cavity; resection is done extra-peritoneally. A hot topic (developed
at Henry Ford Hospital in Detroit) in early 2005 is "da Vinci" (other robotic assistants are ZEUS, AESOP, & Robodoc)
"robotically assisted laparoscopic radical prostatectomy" (RALP), even with nerve sparing.
The robotic technique is (as of early 2006) a marketing "flag"; but, it can do some
anastomotic "wrist action" that is hard for all human laparoscopic surgeons to do as easily
(for the urologist) in a small space. Patient fascination & marketing hype are
responsible for many patient choices to go for the "robot". Check these factors before you think you will
have an all-knowing R2D2-type robot operating on you! It is way too soon (2007) for
longer-term data to prove that RALP has outcome data even equal to OSRP. RALP cannot be
performed if other preceding abdominal surgery or disorders have caused scarring (adhesions)
in the abdominal "insides". RALP came to our area in 9/2007. By 2012, we know that...as with
most endeavors...experience counts greatly with robotics (Fox News "House Calls", Marc
Siegel, M. D. 4/15/2012): Dr. David B. Samadi at Mt. Sinai has developed the SMART
("bloodless prostatectomy") technique with amazing positive statistics as to continence
& sexual function.
For persons who are particularly obese,
transperineal prostatectomy (entering between scrotum and anus) may be "the method" and
usually performed by only a few urologists at major referral centers.
All choices are major surgery, and blood loss
could be significant and require a transfusion (especially with the open methods).
However, transfusions of banked blood can be avoided in the hospital which has: an
autologous blood program,* intra-operative hemo-dilution blood program,* and a
blood-cell-saver program* so that your blood loss is replenished by your own blood. Deep
anesthesia is used. There is a lot of current interest in pain management. Some surgeons
inject the tissue sites around the prostate with a local agent such as Marcaine and
follow this with post-operative pain medications which include an anti-inflammatory
component. Additional or alternative post-operative pain is expertly manageable in
hospitals with IV patient-demand continuous pain medication (PCA*)...patient-controlled
anesthesia...(on it for about 3 days followed by oral medicine for residual pain control)
and/or a program of continuous post-operative epidural pain block* (for about 3 days
followed by oral-medicine for any residual pain control). However, epidural pain block
can sometimes lead to very sluggish intestinal recovery; and, it is very difficult to
rationalize discharging a patient from the hospital who cannot yet properly eat or
defecate. There is a slight chance of death surrounding the stress of surgery.
Hospitalization averages 3-7 days. There is an 80% chance of at least temporary impotence
during the 1st post-operative months and a 30-50% chance of permanent impotence. There
are both medical and mechanical means of dealing with impotence, if it occurs.*
Sparing of the nerves to one or both sides of
the prostate may decrease the odds of permanent impotence in about 50% of cases. We have
had brief experience in about 1997 with CaverMap, an intra-operative electronic
stimulator wand-like gimmick for trying to detect the nerves involved with erection. It
worked clearly in only 20% of cases. Our surgeons felt that experience and a clear
knowledge of anatomy, balanced with a clear knowledge of all of the factors particular to
you and your case, are the best approach to a careful and expeditious nerve-sparing
procedure. The e-coil MRI exam may be most helpful in planning for radical surgery,
particularly in helping to plan the likelihood of successful nerve sparing. The two
programs below probably have the greatest experience at nerve-sparing radical
Laparoscopic surgery tends to allow a more
rapid postoperative recovery. The robotic assistance allows a little better surgical
"wrist action" in forming a smoother anastomosis such that the postoperative catheter
tends to be removable earlier. These are not guaranteed advantages and may not be big
advantages. It will take years to gather data to prove that recurrence rates are no worse
than open prostatectomy. I think that the rush by many internet-savvy newly diagnosed
prostate cancer patients to fly to places to have robotic-assisted laparoscopic
prostatectomy reflects the fascination of the Star Trek generation with the possibility
that robots can outperform humans (forgetting that there is a fallible human operating
the robot...just as a jet pilot operates a jet airplane). Unless a hospital program can
do about 150 or more cases per year, the procedure tends to be sort of "break even",
institutionally...unlikely to last in lesser market places.
Radical surgery is the only treatment allowing
us the extra advantage of knowing if what we estimated, "looking through the key hole",
was correct...and that comparison only when the surgery specimen is examined by a
knowledgeable, interested, and thorough pathologist*. If the "key hole" grade estimate
was faulty, we can find out and adjust the management game plan (the grade gets
"up-graded") towards the future.
The odds of annoying or significant
post-operative complications such as urinary incontinence or urethral stricture are low
BUT: If the pathology exam
indicates cancer in the surgical margins or risk that cancer was left behind, XRT can be
added postoperatively. It is advised by some to do the XRT without necessarily waiting to
see if the PSA rises. But, don't do it prior to postoperative recovery from
urinary incontinence (usually not prior to 3 months...but I'm told that an early 2006
report suggests that its best not to delay).
Premier Programs in the U.S. have included: Stanford University, Stanford, California and Johns Hopkins in Baltimore,
Radiation Seeds: Rule
of thumb: if you have previously had a TURP for any reason, you are unlikely to be
a candidate for seed implant because the complication rate is so much higher.
Called "interstitial radiation therapy" or "brachytherapy", seeds of every type
can now be accurately placed into the gland with U/S visualization. Radiation
beams into gland from within the gland. The advantage here is the delivery of a
compact, high dose of radiation while limiting exposure to surrounding structures
such as the rectum. With a decision for seed therapy (whether permanent or HDR),
precise prostate volume and shape measurements must now be made with another U/S
session, see differences, below. IMRT & IGRT accomplish about the same thing
but deliver from externally.
In order for treatment success rates to
be comparable, the 10 year survival rate is the key benchmark. Much data is
available on gold seeds, the actual "gold standard" (short half-life, deep gamma
penetration) by which any other radiation seed survival data will eventually be
compared. However, even with gold seeds, much of that older survival data was
based on open-abdomen, operative seed implantation which could not be as accurate
as modern transperineal implantation by U/S guidance. Newer isotopes have some
attractive features, but survival data has accumulated for a lesser period of
years. Note that use of a high-penetration isotope such as gold will not demand as
much precision, meticulousness, and compulsiveness of the radiation oncologist and
urologist team as will the short-penetration isotopes (iodine or palladium).
We use palladium seeds. As with e-coil
MRI, our pathologist may be asked to render a schematic of the biopsy findings in
order that the radiation oncologist physician and the physicist have optimal
opportunity to consider and execute any seed additions or special pattern
arrangements based on the cancer distribution in the prostate gland as suggested
by the biopsy findings [even so, the whole gland is treated under the presumption
that prostate cancer tends to be a multifocal disease].
In our program, real-time ultrasound
images and 3D-generated images are evaluated; and the urologist, radiation
physicist, and radiation oncologist (in the operating room, at the time of
surgery) consider numerous factors in deciding whether or not to over-ride the
computer-generated designation of seed placement. There is no delay of days or
weeks between measurement and seed placement during which there could be slight
prostate changes and , almost certainly, re-positioning of the ultrasound probe
slightly differently than at the measurement session. That is, we do measurement,
planning, and execution of surgical seed placement all at one sitting. (Be aware
that there are at least 3 patterns of seed placement that can be used: uniform,
peripheral, and "peripheral plus periglandular").
After final, time-consuming, meticulous
seed placement of upwards of 100 seeds via 24 or more carefully placed needles by
the urologist, a permanent image is taken to document correct seed placement; some
days later, another image is taken to be sure that the proper seed pattern has
continued in place.
Meticulousness is essential because
only a 10-25% under-dosage is said to leave the patient at a 2.3 fold risk of
recurrence...25% under-dosage, 6.7 fold risk! And, a lesser level of
meticulousness probably means that one should be quicker to use XRT overlay...such
double radiation adds 2-3 percentage points of increased risk of serious bowel or
bladder injury. Our program relatively seldom uses combination XRT/seeds.
But, we now have the PSA test to help
with early detection of most treatment failures...regardless of the type of
treatment... so that one may be safer in opting early for new treatments. NOTE: a
phenomenon called "PSA bounce" may be seen in seed-implant PSA follow-up...in as
many as 35% of patients. Within a year or two after seed implantation (median 18
months), the PSA having been down, starts to rise for 12 months or more, the
median PSA increase being 0.4 ng/ml, with a range of 0.1 to 15.8 ng/ml. About 22
percent of the men had more than one bounce. Biopsies are problematic because
cancer cells which have been shocked but not yet eliminated can be seen in the
biopsy in "bounce" situations and don't really mean recurrence. A true cancer
recurrence rise happens later, at a median of 30 months after seed implant.
Be warned that some practitioners
(elsewhere) of this seed method are known to take on marginal, even
contra-indicated cases and almost routinely refer for added XRT (where XRT would
have been sufficiently comprehensive alone)...such urologists get their pay for
seed treatment and also divest [to the radiation oncologist] themselves of patient
follow-up responsibility for at least 2 years! Or, they may much more hurriedly
and imprecisely place the seeds and rely on XRT to mop up whatever was missed.
They may even have a way to make money from both the seeds and the XRT (RCOG has
even come up with an "eye catching" name for their ploy, ProstRcision). Such
entrepreneurial types are often beloved by the patients because, in fact, they are
expertly sensitive as to how to please patients.
XRT overlay is legitimately more likely
if high confidence the cancer is organ confined but Gleason score is 8 or higher
(or there is a "significant" amount of Gleason 4 or 5 component), or evidence of
large tumor by imaging (T2b or T2c) or by PSA of 10 or higher, or a biopsy finding
of "significant" perineural space invasion...anything suspicious of increased
likelihood of minor (microscopic) penetration of the capsule.
Clearly, interested and focused
multidisciplinary collaboration...common sense tells us...should be a real
advantage here. We started seeds about 1992 here and ceased in about 2002 &
began again in 2007.
Premier Programs in the U.S. have included:
Seattle Prostate Institute, Seattle, Washington.
Brachytherapy: Whereas radiation "seeds" are left in place, HDR is administered
through a highly radioactive seed which is attached to a wire which is momentarily inserted
into the patient's prostate gland through 24 or more hollow-catheter tubes/needles.
[a website] These tubes have been initially inserted under U/S guidance,
under local anesthesia. Radiation is in place only temporarily, and the amount of radiation
can be varied within each tube. Correct tube placement is verified by CAT scan. This
radiation procedure is performed during several 60-90 minute intervals over a period of
36-48 hours (the needles must be kept in place the entire time, sutured to the groin). As
with stationary/permanent seeds, you may not be a candidate if you have previously had a
TURP. The balloon-placement, radioactive liquid HDR method now available in breast and CNS
tumors is not applicable to prostate.
Premier Programs in the U.S. have included: Swedish Cancer Institute of the Swedish Medical
Center, Seattle, Washington.
- Medical: CHD (combined hormonal deprivation) or TAB (total
androgen blockade) avoids major surgery and radiation but, while being used, guarantees at
least temporary complete impotence. Menopause-like symptoms can be severe. And, there is the
theoretical chance that CHD/TAB might stifle/kill only the "better" portions of your cancer and
leave behind (or select out for further survival) only any "worse" areas...being left to take
over. r. Fernand Labrie (a Canadian endocrinologist @ U. of Quebec) is/was a
leading proponent of hormone-only treatment.
CHD/TAB is beginning to be used as "neo-adjuvant therapy"*to shrink the gland (reduce tumor
bulk) prior to surgery, seed implant, 3D-CRT, IMRT or cryo-ablation...reduced size means less
tumor to kill and, in the case of any type of radiation, smaller radiation fields (possibly
leading to less chance of complication).
Premier Programs in the U.S. had included: Dr. E. David Crawford's @ Univ. of Colorado Health Sciences Center,
Therapy by External-Beam (Photons/X-rays): XRT has undergone tremendous advances in
the past 20 years, even since 1990. The ability to very sharply focus the photon/x-rays beam to
make its energy concentrate predominately on a precisely defined internal area has become
greatly enhanced and is now available in radiation oncology services which have the equipment.*
The volume of treated tissue (when excellent, highly modern equipment is used) more closely
corresponds to the target tumor tissue.* So, expert radiation oncologists with such equipment
and highly qualified technical teams* have markedly reduced the old side effects and added to
cure rates while delivering increased dose to the target area. The cure rate is high in those
same situations qualified for radical surgery on the basis of Gleason score and cancer stage,
with many experts (both radiation and surgeons) considering excellent XRT to have the same "go
for the cure" possibilities as excellent radical surgery. XRT is a way to avoid radical
surgery; however, the initial use of XRT nearly always voids the possibility of using radical
surgery later (except for "salvage prostatectomy"). But cryosurgery is now available* if XRT
fails. Our professional interest and technological equipment is as high quality as nearly any
in the country.* The odds of permanent impotence are 20-30%. The odds of annoying or
significant complications such as bladder or intestinal injury, urethral strictures, or chronic
pain are low and manageable.
If, by way of higher PSA levels, PSI positivity, higher Gleason score, or other factors one is
suspicious that the cancer may have locally and occultly invaded the capsule, one can "unfocus"
this treatment to the desired degree.
Our Radiation Oncology Department utilizes CT
scan, 3-D planning and delivery of the external beam therapy as of April of 1997
(3D-CRT...conformal radiation therapy)*. Furthermore, such delivery of XRT includes (as
of 2006) use of a multi-leaved columnator, a device which will allow dynamically varying
3-D delivery of even-more-focused radiation to a significantly irregular-shaped and
tightly defined target area (intensity modulated radiation therapy...IMRT). Because the
XRT beam reshaping is automated and dynamic, patient repositioning is minimized; and each
treatment session is time-minimized. Combined with pulse/beam radiation modulation
(varying of radiation dose/intensity), certain areas of the prostate... those areas
containing definite tumor or tumor closest to the capsule, for example...can receive
boosted radiation in a highly optimized manner so as to vary the radiation similar to HDR
brachytherapy.** In 2007, we added respiratory gating capability to IMRT. This type of
external beam refinement is likely to achieve its most optimized potential when combined
with a staging process such as e-coil MRI with oriented prostate biopsy MRI correlation
(as is already being practiced in our institution).
Also, when studies indicate a very localized
cancer, a radiation equivalent of "male lumpectomy (see below...cryosurgery) is possible
with high-dose "boost" to that localized area (if MRS meets researchers' hopes, see
above...surgical options...it might help select cases for special focal/focused
The focus of IMRT & IGRT should come very
close to what is theoretically possible with protons, below.
Premier Programs in the U.S. include: Fox Chase Cancer Center, Philadelphia, PA.
- Proton-particle Beam (radiation) Therapy: PBT is an
external-beam technique and is by far the most expensive type of radiation therapy and is only
currently available in about 10 treatment centers in the USA (as of 2011). It is one of the LET
(linear energy transfer) treatments. The radiation energy can be focused somewhat more tightly
than by other methods because greatest energy is delivered at the end of the calculated path
(the Bragg peak). When this form of radiation is used to treat tissue which is totally
non-movable, the focus can be extremely precise. However, until methods are available to more
precisely and confidently assure that the prostate cancer is definitely confined within the
gland, we have significant concern that such tight focusing of the tumor treatment area could
leave small nests of tumor out in the untreated shell of surrounding "periprostatic" tissue.
Also of significant concern is the fact that the prostate gland (particularly the base or
seminal vesicle aspect) is significantly mobile and could shift in and out of the extremely
focused treatment target area during the multiple treatments, and that any attempt to keep this
from happening may be less precise than one would hope. Furthermore, the urethra, as a highly
important normal structure subject to complications, runs right through the target field just
as with XRT and radiation seeds. IMRT & IGRT, above, can almost as precisely focus as PBT.
By May 2011, one of our urologists had four patients who had been sent to University of Florida
PBT program in Jacksonville for PBT and had excellent
Premier Program originally in the U.S. was/is @ Loma Linda University Medical Center Department of
Radiation Medicine, Loma Linda, California; (also at Harvard
- Cryosurgery: Rather than inserting radiation seeds, freezing
probes are implanted by U/S guidance; and freezing of part of or the entire gland is performed
under U/S visualization so as to kill the cancer but avoid damaging surrounding structures. The
urethra and rectum are protected by heating devices. Unlike radiation, it is possible to use
cryoablation more than once in the same patient. This old treatment has much better modern
control with U/S imaging guidance. As of 1995, there is nationwide caution as to its use except
when the gland is less than 75 grams size, the patient is older than 70 and refuses other
treatments, or there has been local failure of another primary treatment (such as surgery,
seeds, CHD, or XRT). There is more current wide-spread acceptance of cryosurgical treatment of
cases which fail cure by other primary treatments. My radiation oncology friends tell me that
there is an incorrect view circulating that advocates primary treatment by cryosurgery, "Then,
if that fails, you can get radiation therapy."...as if radiation therapy becomes an, "Oh, by
the way..." ready backup for failed cryosurgery. I'm told that this casual attitude is not so
and that "salvage" therapies are what backs up any failed first-line treatment. The following
two programs are seriously involved in first-line, primary treatment by cryosurgery. Even focal cryosurgery has been tried.
Premier Programs in the U.S. have included: @ Allegheny General
Hospital in Pittsburgh, Pa.; @ Crittenton Hospital, Rochester, Michigan.
combination sequence: CHD for a period of time prior to radical surgery is gaining
some popularity because of some initial hopes that the maneuver will "mature" certain higher
grade cancers down to a lower grade and will "down-stage" certain cancers from a higher stage
to a lower stage. Another example would be CHD followed by either of the types of
brachytherapy, followed by XRT.
Testing for Recurrence:
The test for total PSA (see monitoring, below) is
the test of choice, and what you are looking for is "biochemical recurrence"...the total PSA
level rising to 0.2 or higher. CPDR is developing on-line calculators (nomograms or
algorithms) that predict your 5 & 10 year survival likelihoods if your have PSA
recurrence nomogram. On average, it is said that it takes about 8 years from
biochemical recurrence to "clinical recurrence", if no treatment is undertaken. Some of the
reporting nomenclature at very low levels can be confusing. If your treatment was seeds, see the
scary post-brachytherapy (seed implant) benign "PSA bounce", above.
Recurrence = Treatment
Treatment failure is more likely if your
situation or cancer has:
- greater than 20%
Gleason 4-5 component in biopsies,
Gleason scores 8 to 10,
- seminal vesicle
- large size (a
greatest tumor size dimension of 1.0 cm or less tends not to fail [Renshaw, Cancer 83:748-752,
- greater than 15% of
the radical prostatectomy gland is involved or occupied by cancer,
- impressively high
pretreatment PSA level (greater than 10 being the beginning of concern),
- positive lymph nodes
- impressive amounts
of perineural space invasion in a radical surgery specimen,
- evidence of
impressive invasion beyond the capsule, or
- evidence of
significant (not just minute microscopic, technicality-positivity) surgical margin positivity
in a radical surgery specimen,
- advanced stage
higher than T2.
Treatment failure is
searched for...monitored for...by periodic post-treatment lab testing for total serum PSA
levels...tracking the PSA velocity & doubling times. If your treatment was seeds, see the scary
post-brachytherapy (seed implant) benign "PSA bounce", above.
Based on many factors, your treating physician
will determine a monitoring schedule. As previously stated, attempting serial following of
PSA tests gets more complex if you use several different labs (we allow self-ordered testing
in our community [HERE]). In many cases, the post-treatment PSA level does completely
disappear or become negative or zero. Again, your treating physician will have a "feel" for
whether it falls as low as expected for the particular mode of treatment. This is an area of
navigation of the "gray zone". What one looks for, thereafter, is a rising PSA...not just a
single level barely higher than the previous. A velocity greater than 0.75 ng/mL/yr or doubling
time quicker than 10 months is worrisome. If your treatment was seeds, see the scary
post-brachytherapy (seed implant) benign "PSA bounce", above.
All lab tests have detection ranges within which
results are reliable and reproducible. Hardly any are able to detect ultra-tiny amounts of
any particular agent with reliability. Laymen and many health professionals are miss-educated
into the belief that a test can actually be truly negative. In fact, "negativity" is a status
assigned when a test is "non-reactive" at a clinically and analytically appropriate detection
limit which is set at a dependable cut off. Labs express "negativity" in several
- "negative"...(practical; not scientifically or legally clear)
- "non-reactive"...(practical; a little more scientific and legally
- "negative at
0.1"...(more professional, scientific, and legally correct/clear)
- "non-reactive at
0.1"...(more professional, scientific, and legally correct/clear)
- "undetectable at
0.1"...(more professional, scientific, and legally correct/clear)
The above means that an
observer or reader of the lab report of the 1st or 2nd has no scientific idea at what level the
test would "turn positive". In either of the 3rd, 4th, or 5th, the PSA could "creep" from 0.003 to
0.05 and still appear to be "negative"; only after it rises above 0.1 would it become reliably and
reportably positive. And, we know from a practical clinical standpoint that this typical PSA
detection limit serves patients perfectly well. Especially in view of the mathematical law of
"significant digits", a more sensitive method is not clinically
As you read scientific studies, information from
prostate cancer advocacy or support groups, information from the American Cancer Society, and
information from personal or any other sources, remember that rapid changes are taking place
in the details of each treatment modality, combinations of treatments, who the experts are,
and where the premier programs are. You need to be satisfied that: your doctor cares
particularly about your situation; you've soul-searched yourself and revealed your TRUE cares
and fears to your doctor; you feel confident that your doctor is committed to keeping up with
what's available; you have gotten all the reliable information you want to have from sources
committed to keeping up with issues important to patients; and, that you are comfortable with
testing programs, hospitals, or treatment programs selected for your case. You need to
remember that all information sources (including professional persons, programs, and
institutions) tend to be at least somewhat biased (for any of hundreds of reasons). You are
the customer/consumer/ buyer. Hear your advisors; develop your confidence; help choose your
* Available in
Lexington Medical Center Program
** Available in
referral from Lexington Medical Center Program
*** Available in referral lab
from biopsy material processed in Lexington Medical Center Lab.
Prostate Cancer Research
Institute in Los Angeles, Calif.
National Network of Prostate Cancer Support Groups
American Cancer Society
US TOO! International, Inc.
PAACT (Patient Advocates for Advanced Cancer
Attempt to see a copy of the following short
article discussing the screening controversy in Oct. 2011: Brett AS & Ablin RJ,
"Prostate-Cancer Screening — What the U.S. Preventive Services Task Force Left Out", New
England Journal of Medicine, 26 Oct. 2011.
Our pathology group's prostate cancer table of contents page is rich in doctor info (mostly covered
BY THE WAY, have you considered your spiritual status?
(this handout devised July 1995; web site posting
June 1998; latest addition 18 May 2012; some editing & link adjustments 18 December 2015)