PROSTATE CANCER...as I see it...[this
webpage's author]
AT
LEXINGTON MEDICAL CENTER
***give
me
your comments
about this page***
General
Commentary:
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!!!
[create
your free website to keep loved ones posted on your progress]
[skip
down below to PSA, PSA velocity,
PSA density, etc.]
[Online
calculation of your personal risk of prostate cancer.]
[ONE
PAGE PROSTATE CANCER OVERVIEW @ JAMA]
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 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 age 60 or older
already have prostate
cancer they don't know about).
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. You
might even be interested in establishing your own, secure on-line medical
record (iHealth). 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 & create your own free, continually updateable website to
which friends & loved ones can post notes which you & each other can
read.
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:
|
May 2007 Amer. Urological Assn. (AUA) Expert Panel
[here] |
|
riskiness level: |
factors: |
| LOW |
PSA=/<10; & either stage T1c or T2a;
& Gleason
score/sum 6 or less. |
| INTERMEDIATE |
PSA=10-20; or stage T2b (but not qualifying otherwise for higher risk); or
Gleason score/sum 7. |
| HIGH |
PSA=>20; or stage T2c; or Gleason score/sum 8-10. |
***REMEMBER:
PROSTATE CANCER IS NOT A MEDICAL EMERGENCY!***
MOST
CASES OF ELEVATED PSA ARE NOT CANCER!...see
below:
In most areas of medicine, scientific and
practical research are proposing both new tests and approaches 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 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.
Here are our area doctors who can help you [here].
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 or cancers with small
outgrowths a way 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 untested.
WHO
HAS PROSTATE CANCER?
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) have prostate cancer (whether they know it or
not), a prostate cancer prevalence of 1.3% of our general population. In 1997,
170 were expected to die, and 300 will 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. It used to be diagnosed mostly when metastatic 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
below).
HOW
MIGHT A PATIENT THINK ABOUT THIS SITUATION?
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 zones.
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
has a friend in another state who called with the unsettling news that his PSA
screening test came back with results in the thousands; his biopsies showed
Gleason 5+5=10 cancer...5 years ago (1997). His PSA is undetectable today. 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. Are
you recruiting God to help you? 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 are!
READING
AND PERSONAL RESEARCH:
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 WHOM?
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. [comments below] 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. 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. A highly significant component
of whether "satisfactory results" have been achieved rests on the
satisfaction of you, the patient.
HOME
TEAM ADVANTAGE:
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 [about
"point-of-service pathology"].
:::::::::::::::::::::::::Screening::::::::::::::::::::::::::::
SHOULD
YOU EVEN BE SCREENED FOR PROSTATE CANCER?
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 elevated.
SCREENING IMPLIES DEALING WITH RESULTS:
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. Recent studies show 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? 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 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.
GET SCREENING TESTED WHILE YOU ARE
WELL!
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); 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. The e-coil MRI (below) may help find the cancer; see "PSA
parameters", below.
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 was
dishonest, 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 in early 2005.
:::::::::::::::::::::::::Diagnosis::::::::::::::::::::::::::::
WARNING!!!
THE FIRST STEP...DIAGNOSIS... IS CRUCIAL!
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 is available
through all of the Columbia-area urology groups and the radiology group at
Lexington Medical Center. 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 evaluation should a patient elect
treatment at a program anywhere else in the world.
Findings justifying (or being indications
for)
biopsy:
 | if you have an abnormal DRE |
| 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 level.
PSA
PARAMETERS:
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 41and 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". |
| Density (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 (here)...below 0.15 is comforting, 0.15-0.18 is
concerning, & 0.18 or higher warrants a biopsy)...this parameter is less
reliable with 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). 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.
|
| Velocity (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 all. |
| Doubling 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 |
CORE
BIOPSIES:
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 nerve blocks on all of their cases in about March 2007.
Patient preparation consists of the patient:
| completely emptying the rectum with an enema (such as Fleets phospho)
about an hour before the biopsies; and, |
| starting an oral antibiotic to begin the day before or no less than
about 2 hours before the biopsies (note
here). |
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 biopsies:
But, will
the pathologist SEE the cancer? And,
will their lab operation assure that specimen mixup 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, only some of the pathologists in our group are
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 (double reading).
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 paper).
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 length.
The Gleason "grade" for primary
treatment decision making is interpreted from the biopsies, see below.*
Biopsy problems with "ASAP":
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 diagnosis.
CRUCIAL
POINT: Patience needed
!
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 the straw!
##########Now, How Bad Is
It?###########
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 Kattan nomogram 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 situation?
Treatment
recommendations/decisions rest on three broad parameters:
- the patient's general
health status: the healthy do better than less healthy.
- 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 bullett) 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 older.
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).
:::::::::::::::::::::::Cancer
Staging::::::::::::::
Measures:
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.
- PSA levels: the higher the PSA, the more likely cancer has spread out of the gland.
- Bone 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 bones.
- U/S positivity: an
insensitive, but sometimes positive method to show cancer escape from the gland.
- endo-rectal-coil MRI positivity: a parameter that can pick up extra-capsular extension.
- DRE 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).
e-coil 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. In addition, the body-coil 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:
1.
When doctor desiring to locate a likely target
for biopsy in PSA "high rollers"
(see "screening", above).
2.
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.
3.
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,
4.
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.
ProstaScint* 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. 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:
ADDITIONAL KEY OBSERVATIONS:
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:
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.
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 patterns:
 |
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.
|
|
Gleason score "badness":
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 all:
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 already?
What is the probability, by Gleason score alone, that the cancer is still locked inside the
prostate gland? If biopsies show:
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 factors?
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 nodes.
What about proportion of Gleason 4 & 5 pattern?
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 follows:
| Bad-grade 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 therapy. |
| Good-grade 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.
|
| Uncertain cancer: If
biopsies have some Gleason 4 or 5 component, but less than 20%, it is a gray
zone.
|
NOTE: 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
examples:
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 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 over a decade 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. And
we have access to, and practice on, the Johns
Hopkins grading tutorial. 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 Advertising:
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
tactics.
Perineural
Space Invasion:
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 penetration.
Proliferation
Rate (how fast it is growing):
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.
(We are almost never involved in such Ki67 determinations).
DNA
testing:
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 requests).
P27
proliferation "brake" marker:
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 March 2005).
(We are almost never involved in such P27
requests).
rt-PCR-PSA test:
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:
| favorable/better 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). |
| 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. |
Summary
Point:
Your doctors try to categorize your cancer
situation as
"better", "worse", or "uncertain" in order to plan
your treatment and management.
HOW
LONG WILL I LIVE?
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 cancer.
:::::::::::::::::::::::::Treatments::::::::::::::::::::::::::
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 You:
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 [online
calculator]. 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.
TREATMENT-DECISION BLOCK:
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 herbicides).
FIVE
INTERNET SOURCES POSSIBLY HELPING TO ORGANIZE YOUR THINKING TOWARD DECISIONS...COMPUTER
DECISION AIDS:
| Prostate
Cancer Profiler is 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 "decision trees".
|
| 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 time.
|
TREATMENT OPTIONS LIST:
CH's
website thumbnail overview of the common treatment options.
| 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 biopsies).
|
| Surgery:*
open or laparoscopic radical prostatectomy with bilateral nerve sparing.
|
| Surgery:*
open or laparoscopic radical prostatectomy with one-sided nerve sparing.
|
| Surgery:*
open or laparoscopic radical prostatectomy 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
session).
|
| 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 (IGRT). |
| Radiation: Cyberknife (highly focused robotically aimed external radiation
with gating)...has advantages over the Gammaknife. |
| 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 foo") |
| Planned
combination sequences.*
|
a.
Pre-radical-surgery neoadjuvant CHD.*
b.
Combination seeds and XRT.*,**
c.
Other sorts of combinations.*,**
| Fall-back"
combination sequences or salvage procedures.*,**
|
| Other
treatment maneuvers:*,**
|
a.
Bilateral orchiectomy (castration)*
b.
Radioactive strontium*
c.
Spot XRT to bone lesions*
d.
Vaccine therapy (Johns Hopkins University)*
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 cryosurgery...cryoablation.
Good layman articles
about how they made their choices in May 13, 1996 issue of Fortune magazine.
Some
Rules of Thumb About Each Treatment:
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, 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 younger men). Or 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.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
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 increase in PSA), then treat with curative intent.
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
frought 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) mostly a marketing gimmick; 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 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 9/07.
For persons who are particularly obese, transperineal prostatectomy
(entering between scrotum and anus) is 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
prostatectomy.
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 and manageable.
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. include: Dr. Tom Stamey's @ Stanford University, Stanford, California
and Dr. Pat Walsh's @ Johns Hopkins in Baltimore, Maryland.
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 "eyecatching" 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. include: Dr. John Blasko's @ Seattle
Prostate Institute, Seattle,
Washington.
[Seedpods
info site...urologists doing "seed" implants].....[an
example of a free-standing prostate facility]
HDR 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. include: Dr. Timothy P.
Mate's, 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. Dr. Fernand Labrie
(a Canadian
endocrinologist @ U. of Quebec) is a leading proponent of hormone-only
treatment.
CHD/TAB is beginning
to be used as "neo-adjuvan