Tuesday, August 20, 2013

Employers, health insurance coverage and PSA testing

Help me with this please.

A 56-year-old man just got a new job. As part of the pre-employment process and in order to be covered by his new company's health insurance, he had to undergo a physical examination and some blood tests. A digital rectal exam was not done.

He has no risk factors for prostate cancer or urinary symptoms and by most guidelines is not a candidate for PSA screening.

He was not told of the possible harms of the test, nor was he told to abstain from ejaculation within 48 hours of the blood being drawn.

Of course, his PSA is 5.9 ng/mL.

The cost of the repeat PSA test will be borne by the patient. There is already talk of biopsies.

Not only will the patient have to deal with the anxiety generated by the test, he is being pro-rated by his health insurance carrier. He will be paying $200 per month extra for his coverage.

Does anyone have any thoughts about this?


CholeraJoe said...

A pre-employment physical must relate to specific requirements of the job. Unless he was applying to be a pornstar, I fail to see how a PSA relates to job requirements.

Skeptical Scalpel said...

Joe, he's not going to be a porn star. It's a sales position.

artiger said...

I read an interesting piece on Medscape a few days ago about the lost skill of physical examination. I have to wonder if insurance company medical directors forgot their exam skills when they accepted their positions.

A much as I abhor our legal system, if I were the patient, I would be tempted to confer with a seasoned health care attorney, or perhaps even discussing this with the state insurance commissioner. Of course, that would probably be the end of the new job, but it's the principle of the thing, on several fronts.

Of course, if the guy winds up having prostate CA, the insurance company will probably want to be thanked for saving his life....

Skeptical Scalpel said...

Artiger, regarding your last point, it is unclear that screening PSAs really save lives. No one knows which prostate cancers are lethal and which are indolent and would not have ever harmed a patient.

Anonymous said...

Insurance should pay for the 2nd test, and the patient be informed on correct preparation. Then go from there.

Anonymous said...

Skeptic, you are flat out wrong here.

See the results of the esrpc trial. Over 150k men randomized, found that 1 death was prevented for every 1000 men screened (better than the nns for colonoscopy and mammogram)

artiger said...

Scalpel, you and I know that, but try convincing the patient. You know how lay people react to the "C" word. And obviously the insurance company is doing little to educate him.

Skeptical Scalpel said...

Anon #1, I agree but they won't pay for it.

Anon #2, 1 death prevented for every 1000 men screened but how many are harmed? Here's an interesting analysis of the ESRPC trial http://bit.ly/18JHGOA.

The ESRPC trial authors said that after adding 2 years of follow-up data to the data originally published in early 2009, that “PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality.”

The analysis says, "Screening can prevent between 20 and 30 percent of prostate cancer-specific deaths. From the alternative point of view, one can argue that screening a million men would indeed prevent about 950 prostate cancer-specific deaths, but would also lead to the potential over-treatment of 36 out of every 37 cases of prostate cancer identified, and would have no impact whatsoever on overall mortality.

Artiger, that is the fallacy of "watchful waiting." Many patients are not comfortable with it.

Todd J. Scarbrough, M.D. said...

Here's why I think PSA screening is being improperly "picked on." In no particular order...
1) Of all malignancies known to man, prostate cancer (CaP) has had the biggest decline in mortality rates over the last 50 years. Really huge declines. This did not manifest 'til the 1990s, the beginning of the PSA era. Is this mere coincidence?

2) "Anon #2, 1 death prevented for every 1000 men screened but how many are harmed?"
I shall now give you my biased opinion, although I shall attempt to back it up with fact. Here is an idea of the "harms" present circa 2013 with modern radiotherapy (http://astro2007.abstractsnet.com/aresults.wcs?entryid=500334, http://www.advancedradiationcenters.com/docs/prostate2.pdf). There are potential harms present in any screening program. I think the risk/benefit ratio is well balanced nowadays.
3) There is no lobby for prostate cancer like there's a lobby for breast cancer. If there were, all this talk about trashcanning the PSA screen would not be happening.
4) There was a time when men would be in hospitals with prostate cancer growing into their bladders, rectums, pubic rami; and these men were SICK. We really don't see that anymore.
5) Prostate cancer varies across populations (http://jco.ascopubs.org/content/31/24/2991.abstract). Be careful about throwing the baby out with the bathwater, as they say.

artiger said...

Dr. Scarbrough, quite true (about lack of an effective lobby for prostate CA, although there has been some quiet rumbling recently). Remember the outrage when the preventive task force had the audacity to suggest that mammograms be done later and less frequently?

DD said...

With all due respect Dr Scarbrough, the responsibility for the lack of an effective lobby (for Prostate CA) falls on the group this issue affects, right?

Men need to promote prostate cancer awareness, screening exams for early detection, and timely treatment. If it takes a blue "ribbon" campaign,and 'race for the cure', then so be it. Educating the public takes an organized effort; it is my contention that men may listen more closely to what other men say about this uniquely male disease.

Skeptical Scalpel said...

I need to point out that Dr. Scarbrough is a radiation oncologist.

What exactly do men have to lobby about here?

Anonymous said...

The question is whether *screening* for prostate CA saves lives. The overwhelming evidence is that it does not. PSA and rectal exams are not effective.

It is disappointing to see how many physicians are statistically lacking.

Anonymous said...

The recommendations about screening mammograms were on target. Just because there is a large, loud lobby yelling otherwise doesn't contradict the science.

Skeptical Scalpel said...

Anons, thanks for commenting. No argument here.

Anonymous said...

Prostate cancer comes in two flavors: the "live with it" flavor and the "die of it" flavor. The former doesn't need treatment. The latter isn't helped by treatment.

I'm a 66 year old medical oncologist. I've never had a PSA test. I'll never get a PSA test. If I were to get a PSA test I'd have a Russian roulette chance of getting transrectal needle biopsies. If I got transrectal needle biopsies, I'd have a Russian roulette chance of getting my prostate whacked out, zapped with ionizing radiation, frozen, or cooked. If I got any of the latter I'd have a very high probability of incontinence and/or sexual dysfunction and/or bowel problems and a vanishingly small probability that the whole exercise and associated misery would save my life.

With regard to falling rates of prostate cancer deaths, there has been a precipitous decline in cardiovascular mortality beginning in the early 1970s and part of this has been attributed to dietary changes which could also have affected the incidence of prostate cancer, for all we know. That's why the only reliable data are the prospective randomized trials -- and those trials have convinced me, personally, that I don't want to have PSA screening, for reasons explained above. - Larry Weisenthal/Huntington Beach CA

Anonymous said...

I recently attended a week-long "Family Medicine" update given by a big-name university. It is not my specialty but every once in a while I take an out-of-field CME just to see what is going on. Interestingly, only one lecture was given by a FP; every other presentation was by specialists. (So, is Family Medicine a real specialty?)

The presentation about breast cancer basically said that routine mammography doesn't save many lives, but the political reality is that PCP will have to keep doing them. The newbie is now expanded BRCA screening,which is recommended for a Jewish woman with even *one* 1st degree relative with breast CA .

The prostate CA lecture was given by the university's director of urological CA. He acknowledged that studies have shown that screening doesn't work well. BUT: if you extend the follow-up to 20 instead of 10 years, then screening saves lives. Plus, he will recommend follow-up instead of operating like his less competent colleagues.

My impression: BS.

OT: This was the only medical course-given by a major medical center-I have ever attended (and I have gone to plenty) where lecturers have actively tried to recruit referrals. The culprits were all surgeons.

Old Rockin' Dave said...

I will toss my anecdote on the scale. At age 56, I went for an annual exam. I had no urologic symptoms whatsoever. A digital rectal exam which was negative. The NP noted that I hadn't had a PSA done for a few years and added one to the draw. It came back at 7, considered intermediate by lab standards. A urologist did a fractionated PSA and it was 86% protein bound, almost definitive. At transrectal biopsy, I had 7/12 positive cores with positive cores in all quadrants and a Gleason score of 6. I opted for radical prostatectomy. The surgical path raised my Gleason score to 7. Cancer was found right up to the capsule, judged by the urologist to be on the verge of getting through. Workup and direct observation showed no sign of mets anywhere. PSAs in the four years since have been below detectable limits. My rough risk of recurrence is about 20% over the first fifteen years, then dropping to nearly zero, so I have a reasonable chance of having had a surgical cure. At this point, my quality of life is pretty close to where it was before the surgery. I leak a little urine and I am looking forward to a penile implant. I have seen my daughter graduate from college and expect to see my son do so next year. I might even get to look on the face of a grandchild or so. Even with recurrence I have a pretty good chance of making it to beyond the famous threescore and ten.
This raises the question: without the PSA done when it was, what would my staging have been when I eventually had symptoms significant enough to get worked up? Nodal mets? Disseminated disease in the pelvis? Distant mets? What would my life be like without the PSA? What treatments would I have had to undergo in that other case? What would be my chances of disease-free survival after treatments?
Tell me, "runnswim", which kind did/do I have - the "live with it" or the "die of it" kind? Where do I fit in your dichotomy? Can anyone honestly tell me that I made the wrong choice?
Are screening PSAs cost-effective? Don't ask me - I'm biased. Ask my family instead.

Anonymous said...

Hi Dave,

I'll provide my answers to your questions later today. My name, given in the body of my post, is Larry Weisenthal (please call me Larry), not runnswim, which is simply my Openid login. Thanks for commenting on my comment. Yours is a perfect case to clarify the controversy.

Larry Weisenthal/Huntington Beach, CA

Skeptical Scalpel said...

Anon, very interesting comments. One, FPs don't speak at their own CME course. Two, recruiting referrals, which is probably a lot more common than you think.

Larry and Dave, I look forward to more of your dialogue.

Todd J. Scarbrough, M.D. said...

"If I got transrectal needle biopsies, I'd have a Russian roulette chance of getting my prostate whacked out, zapped with ionizing radiation, frozen, or cooked. If I got any of the latter I'd have a very high probability of incontinence and/or sexual dysfunction and/or bowel problems..."

I'm sad a med onc thinks this. Shows how poorly we've communicated how far radiation has come in the last decade (see some data I linked in above). Treated 1000+ men in my career. One patient has become urinary incontinent. Less than 20 have any bowel complaints from the RT. Most men with sexual function keep it (~75% conservatively). Your experience will likely be different; but there are rad oncs "in the wild" increasingly achieving these metrics.

And sure I'm a proponent for radiation in prostate CA. But it's not on account of I'm a radiation oncologist. I'll be the first guy to say no RT for seminoma, e.g., based on recent randomized data. No RT for older women with low-risk breast CA. Etc. Believe it or not, I adhere to data, not beliefs (not always at least!). Finally, the data lead me to believe that there is reasonable evidence PSA screening (and mammograms, and screening chest CTs, and many other medical screens) save lives.

Anonymous said...

I am just an ICU doc, so a few steps removed from cancer screening.

I have read the opinions of national bodies (who presumably have statisticians and many doctors on board), and read the journal articles myself.

My personal view:

Prostate CA screening does not save lives, but increases various serious morbidity on the tested population (incontinence, impotence).

Mammography saves a few lives, maybe.

Screening chest CT's for smokers: jury is out.

Anyways, why is screening or not subject to the whims of the doctor or NP? Shouldn't there be rational, evidence-based guidelines applicable everywhere?

Skeptical Scalpel said...

Todd and anon, thanks for commenting.

Todd, I meant to mention that the mortality rate for prostate cancer may be declining because the PSA test is picking up large numbers of cancers that would not have been fatal. That means the denominator is a bigger number which gives the illusion that mortality rates are lower. Don't forget that the ESRPC trial authors said “PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality.”

Anon, It is hard to produce guidelines that everyone agrees with unless you do what the urologists did earlier this month. They produced a consensus statement (http://www.bjuinternational.com/bjui-blog/the-melbourne-consensus-statement-on-prostate-cancer-testing/) that, not surprisingly, strongly supported PSA screening. Only urologists participated in preparing the statement. The comments are worth reading.

Old Rockin' Dave said...

Anonymous ICU doc, I did suffer notable morbidity from my surgery, as you can see in my post above. I also suffered a surgical accident that came close to killing me; it could have happened with any pelvic, abdominal, or thoracic surgery, certainly including debulking that I didn't need. Please tell me what morbidity I was spared by having my prostatectomy before capsular rupture. I most likely would have had to have a prostatectomy anyway, possibly with extensive debulking surgery. I might have needed radiation to a broad field with no guarantee it would reach all possible metastases. Maybe I would have needed hormonal/hormonal antagonist treatment, maybe even actual castration. Is there any doubt that any of those, alone or in combination, would have put me at risk for more, and more serious, morbidity more deleterious to my quality of (a likely shortened) life?
I realize that my experience is "just an anecdote", but it is the anecdote of a real, breathing, feeling person. PSA screening doesn't save enough lives to be cost effective? Would you prefer that I had been written off? It was 100% life-saving and cost effective in my case. I am still here and reasonably intact. My mother has both sons, my wife has her husband, my children have their father, my brother has his only sibling, my nephew has his only uncle. Nobody was left saying, "If only someone could have found this sooner."
I dare anyone, policy maker, economist, politician, statistician, whomever, to look me in the face and tell me I should have been sacrificed on the altar of cost effectiveness. As well, I dare any of them to stand over the grave of someone not as lucky as I was and say the same.

Larry Weisenthal said...

Part 1 of 3

Continuing with Dave's anecdote:

Dave's case is classic. It applies to anyone who's ever had a screening test for cancer, where cancer is detected. It happens all the time with screening mammography in breast cancer. The cancer is discovered; the surgeon cuts it out. The patient credits the screening and the surgeon for the cure. But no one knows what would have happened, absent the screening, in an individual case, much less in a population. That's why we need actual clinical trials. We do know that Dave suffered morbidity as a result of his screening and surgery (described by Dave). We don't know whether Dave's ultimate outcome would have been any different.

Let me explain (and apologies to Skeptical Surgeon for taking up so much bandwidth -- the topic defies concise summary).

I want to begin with a personal example/anecdote, since Dave is kind enough to provide his own personal example/anecdote.

10 years ago, my then 89 year old father was swimming in a one mile ocean race. He got chest pain half way through, but finished the race and was able to walk a mile down the beach to retrieve his clothes and car keys.

By the time he approached the staging area, he was obviously in severe distress. Paramedics took him to Broward General Hospital, where he was diagnosed with an acute myocardial infarction, with critical lesions in four different vessels. He underwent a 4 vessel CABG. He was discharged on the "blood thinner" warfarin.

The only problem was that no one checked his blood test to determine proper dosage of warfarin prior to discharge. 10 days later, he felt faint, and collapsed on the kitchen floor, barely able to dial 911 before he went down. Upon presentation to the ER, he was diagnosed with profound anemia, a prothrombin time of more than 100 seconds (indicating profound iatrogenic over anticoagulation with warfarin) and, in the first 24 hours, received 7 units of packed red blood cells.

An extensive work up diagnosed a very early state I gastric adenocarcinoma (source of his occult bleed). He received an 80% gastrectomy, and, 6 years later, set a world age group record in masters swimming in the 200 meter backstroke, 7 years later started day trading on the internet stock market, where he's since earned hundreds of thousands of dollars, consistently beating the market indices. Along the way, he went to several weddings of grandchildren, two Ivy League graduations (Harvard and Yale), watched a granddaughter swim the English Channel in near record time, saw two granddaughters enter medical school (Colorado and Yale), attending the white coat ceremony, and, more than 10 years after his massive iatrogenic bleed and resulting diagnosis of early gastric cancer, is looking forward this fall to attending another granddaughter wedding, as well as celebrating his 100th birthday, while continuing to day trade several hours a day and swim a half hour a day.

Here's a youtube video, featuring him at age 97 1/2:


Here's the documentation for his world masters swimming record:


There is little doubt in my mind that, absent the iatrogenic overdose with warfarin, the gastric adenocarcinoma wouldn't have been diagnosed at the very early, curable stage, and that he'd have been long since dead.

Conclusion: Everyone over the age of 85 should eat rat poison (the active ingredient in warfarin) as a provocative screening test to detect an occult gastrointestinal bleed, which could be caused by gastric or colon cancer.

By the way, here's also some documentation for the case history I just provided:


I presented the above to show how anecdotes shouldn't be used to reach conclusions regarding appropriate standards of medical care.

(continued in next installment):

- Larry Weisenthal/Huntington Beach CA

Larry Weisenthal said...

Part 2 of 3:

Moving on to Dave's case: Dave had a PSA < 10 (considered a favorable prognostic sign). He had Gleason 3 + 4 disease, which is also considered favorable. According the the literature, the period of time between elevation of PSA to the development of symptoms is on the order of 7 years, and this is probably longer for more favorable disease, such as Dave's.


Dave feels that he was on the verge of developing capsular invasion, lymphatic invasion, and vascular invasion, and resulting bone metastases. But invasiveness is NOT a property of geographic proximity to the capsule, it is a property of the biological aggressiveness (invasiveness) of the tumor, and Dave did not have a biologically aggressive tumor.

The issue is whether an early diagnosis (prior to the onset of symptoms or diagnosis on a routine physical examination), leading to early treatment makes a difference.

We have to start out by asking whether or not local treatment, itself, makes a difference. Decades ago, the Veterans Administration Cooperative Urology Research Group (VACURG) did a classic prospective randomized trial, in which patients with prostate cancer were randomized between radical prostatectomy versus no local treatment. There was no difference after 20 years.

The study was criticized by urologists, who said that pre-operative staging methods were primitive in that era and probably a lot of patients had surgery who already had metastatic disease. This is a weak argument, if the importance of local treatment is so great. Surely a lot of the patients in both study arms did not have metastatic disease at the time of study entry. If the surgery was so important, then SOME degree of difference should have been seen. But it wasn't.

Fast forward 30 years. The VA does a more modern trial. Patients diagnosed with prostate cancer by PSA testing. Modern era of pro-op staging. Still no difference between radical prostatectomy versus observation.


What about the situation where you don't diagnose prostate cancer with PSA testing but rather on the basis of the old fashioned methods (clinical symptoms and physical examination, as with the original VACURG trial)? The Scandinavians did a study in which half the patients got a radical prostatectomy right away and the rest either never got one or only got one when they were in relatively dire shape. In this latter study, younger men (like Dave) derived some benefit, while men over the age of 65 did not.

But this study was rightly criticized because the men in the surgery group got much better care (e.g. when the "watchful waiting" group symptoms of progressive cancer which was causing urinary obstruction, they often got only TURPs -- roto-rooter jobs -- rather than definitive local therapy. The surgery group also got better care in cases where advanced disease developed. So this wasn't really a trial of immediate surgery versus delayed surgery only when disease progression occurred; rather it was a study of different levels of medical care.



(concluded in next segment)

Larry Weisenthal/Huntington Beach CA

Larry Weisenthal said...

Part 3 of 3

In the final analysis, however, the proof of the pudding is in the eating, and the proof of the value of PSA screening is whether or not it saves lives. Generously speaking, it possibly saves one life for every 1,000 to 1,500 men who receive PSA screening, according to the consensus evaluation of the prospective, randomized trial data.

Were this to be achieved without morbidity, then it might be worthwhile (and note that, contrary to Dave's insinuation, this is NOT about "cost-effectiveness" and it's not some sinister ObamaCare plot to save money -- it is ONLY about MEDICAL EFFECTIVENESS, or lack thereof). But the morbidity is severe. Dave described his own morbidity. This is very typical.

Why should I get a PSA test, when I have no symptoms, at all? Do I want a bunch of transrectal needle biopsies of my prostate? Do I want to get my prostate whacked out, recovery from which will take up the better part of a year of the best time of my life, at a downstream cost of lingering sexual and urinary side effects, which could be otherwise avoided -- or at least delayed for years? For a lottery (1:1000 to 1:1500) chance that this might help me avoid dying of prostate cancer?

Everyone has to make up his own mind about questions like this. But you've got to start out by understanding the implications and knowing the facts.

- Larry Weisenthal/Huntington Beach CA

Henna said...

My dad had virtually the same story as Dave, above, and at about the same age... No symptoms, jump in PSA, high fractionated, didn't look good at the biopsy. His surgery ended up taking much longer than planned because the prostate was far more enlarged than any imaging showed, and about to burst the capsule. Prior to surgery he felt that his main options were a radical prostatectomy or do nothing. He has been plagued by continual incontinence. I don't know about sexual function but from my (Irish) mother's few veiled comments, I gather that nothing much happens. He is 15 years out and relatively content with the outcome. Again, I realize it's just one anecdote.

Larry Weisenthal said...

I just saw Dave's last comment (August 24 at 1:43 PM). He said:

"It was 100% life-saving and cost effective in my case."

Dave, with due respect, what you say is simply not true (or, rather, very likely not to be true). Contrary to your impression, you were NOT in grave danger of capsular invasion, lymphatic invasion, vascular invasion, bone metastases, and death. You had low grade disease. You had a favorable PSA level. There is a reasonable possibility that you never would have had symptoms, or, if you eventually would have gotten symptoms of prostatic enlargement, you could have then had a work up and diagnosis, with no disadvantage to your ultimate prognosis, and you could have then made the decision whether or not you wanted surgery, radiation, cryotherapy, microwave therapy, or just a TURP and watchful waiting (depending on how old you were and whether, at the time, you had any other co-morbidities. Meanwhile, you could have spared yourself all of the side effects that you endured.

Maybe you would still do it the same way, if you had it to do all over again. It's very anxiety provoking to know that you've got cancer, even if it won't ultimately kill you. But, if you hadn't gotten the PSA test, you might be blissfully ignorant and even happier than you are today. That's the way that I prefer to remain, knowing all that I do.

- Larry Weisenthal/Huntington Beach CA

Todd J. Scarbrough, M.D. said...

"Todd, I meant to mention that the mortality rate for prostate cancer may be declining because the PSA test is picking up large numbers of cancers that would not have been fatal. That means the denominator is a bigger number which gives the illusion that mortality rates are lower."

Hey SS. The mortality rate (http://en.wikipedia.org/wiki/Mortality_rate) is deaths per 1000 people; those people--that denominator--are all well and sick folks (not just the sick folks)... the whole population. Said another way, the mortality rate of prostate cancer is the number of deaths of people with prostate cancer per 1000 male folks, per year.

So let's say in 1990, there were 100,000 people diagnosed with prostate cancer, and 25,000 died from prostate cancer that year, and there were 250 million folks in US; mortality rate: 25,000/250 million = 1 per 1000. Now, in 2010, 250,000 people diagnosed, 30,000 people die, and there are 300 million in US; mortality rate: 30,000/300 million = 1 per 1000.

In this wholly fictitious example I just made up, the number diagnosed skyrocketed, the death rate didn't change though. That is to say, I don't think your idea about the numerator thing is right or a good explanation as it pertains to mortality rates.

you're famous again:

Look, I know I'm swimming upstream. Yet there's still this idea gnawing at me that PSA screening really did change things. I'm yet to feel >95% certain it hasn't. We cite the "underwhelming" randomized trials; I wonder if the "trial" (introducing PSA into the population and seeing what the results are) hasn't already happened, and the p-value is <<<0.05.


Larry Weisenthal said...

Henna makes the same mistake as Dave in discussing her father's case, to wit:

"...the prostate was far more enlarged than any imaging showed, and about to burst the capsule."

This is not the way prostate cancer works. It's not like water filling up a balloon, where pressure from the inside "bursts" the gland capsule. Dave thought that he was in imminent danger of metastases, because of the proximity of one area of his tumors to the capsule. But what determines caspsular invasion (or not) is not geography but rather the intrinsic invasiveness of the cancer cells.

A good analogy is in situ carcinoma in the breast. This is can grow to involve virtually the entire breast, yet not be threatening in any way, because it does not invade the breast ducts, lymphatics, or blood vessels. Low grade prostate cancer (again, like Dave's) may be analogous to in situ breast cancer.

Pathologists have an easy time identifying non-invasive breast cancer, because the tumor cells remain confined to the duct structures. The architecture of the prostate is different from the breast, and there isn't such a convenient marker for invasiveness as whether or not it is confined to ductal structures. Actual invasion of the prostate capsule is an unfavorable sign -- such patients have on the order of a 7 fold higher incidence of developing metastatic disease -- almost certainly because capsular invasion is a marker for the sort of invasion required to develop lymphatic and/or vascular metastases. Again, Dave didn't have capsular invasion, and the mere fact that the tumor was close to the capsule tells us nothing at all of its invasive properties.

That's why the Gleason scoring is so important.

This comes back to my statement that survival in prostate cancer is determined by disease biology, much more than by disease treatment? ("it comes in two flavors; live with it and die of it"). The virtually absent impact of local therapy (radical prostatectomy) was discussed above.

In contrast:

Let's look at prostate cancer specific survival at 10 years, as a function of Gleason score:

Gleason 6: 98.4%
Gleason 3 + 4 (Dave's disease): 92.1%
Gleason 4 + 3: 76.5%
Gleason 8-10: 69.9%


Massive difference for biology -- the Gleason's score, which is a surrogate for INVASIVENESS, which is what determines whether or not the tumor invades the capsule, invades into the lymphatics, and invades into the blood stream and NOT the size of the tumor -- e.g. Dave's 6 positive needle biopsy cores and position within the gland close to the capsule!

We should go on to consider the radiation therapy data -- topic for another time.

- Larry Weisenthal/Huntington Beach CA

Skeptical Scalpel said...

Larry, Dave and Henna, thanks for a very interesting discussion/debate. I appreciate the comments and your sharing your stories. Prostate cancer is a very difficult topic and it is charged with emotion. I think discussionslike this are good.

Anonymous said...

SS, thanks for link to the Melbourne consensus statement on PSA testing, and its readers' comments. As you and others have pointed out, 1)the authors are all urologists, 2) their interpretation of the data contradicts those of other professional groups, particularly USPSTF, 3)some of the Consensus recommendations are vague enough to be useless, 4)the point that diagnosis does not equal intervention will be difficult to implement in practice, as many doctors and(?most) patients will insist on "doing something".

I am surprised that the panel did not include a few biostats/public health types, GP's/internists (they are on the front lines), and radiation and med oncologists. Then the result might have been more of a Consensus rather than a closed group reaffirming each other's believes.

Anonymous said...


I hope this does not come off as sarcastic, but I am genuinely puzzled:

I agree that Gleason scores are just markers for biological tumor activity, but in that function they do pretty well. But, if local treatment is mostly ineffective, then does it matter whether if the Gleason is 6 or 10 at first diagnosis absent mets?

In other words, what if we move questions about PSA screening one step further. Does treating Gleason 6 vs Gleason 10 save lives?

Old Rockin' Dave said...

Larry, I need to add a few comments in response.
First, you are assuming my Gleason score was 3+4 and not 4+3, or even 5+2 (not likely, I know). As you know, pathologists can disagree. The biopsy was read as a 6 originally, but a second opinion gave it an 8, and the surgical path scored it as a 7. I have been going by 7 as my Gleason score, but it may have been higher. By the way, I had 7 positive cores, not 6, from all four quadrants. This is suggestive of multiple foci of disease, which has it's own implications.
As you and I both know, aggressiveness correlates with age at diagnosis. Having worked under Larry Norton, I have some basic, minor grounding in growth modeling, and I think it's safe to say that while a Gleason score of 6-8 is not the worst, at 56 it is different from the same score at 75 or 80.
You also mention "the proximity of one area of his tumors to the capsule". I said nothing that allows you to draw the inference that it was one area. The surgeon said there was a very large amount of tumor in my prostate (suggesting to me a doubling time toward the shorter end) and not only wasn't he sure he could spare the nerves, bi- and not unilateral, he wasn't even sure that he had gotten clean margins until the path report. It was not "close" to the capsule; it was distending it. The GU that did the diagnosis and the one that operated are not connected professionally or personally; both are of the opinion that I was at imminent risk of capsular rupture - weeks to months, with significant, certainly non-zero, risk of intrapelvic dissemination, and possible distant mets not very long after. These gentlemen have a great many years of experience inside and out of the OR; they are familiar with my case and I defer to their judgment. The diagnosing GU has a long history with my family, both as physician and as parent of a patient. Since he didn't operate, has no need to make the other urologist look good (I dislike the other guy greatly, and with reason, and his entire department as well), and knows we value him for his candor, I am as certain as I need to be that he is not shading the truth in any way.
Surgery was my choice; I could then preserve radiation as a future option, meaning less potential morbidity than the other way around. I was not thrilled with other forms of ablation, and in retrospect I believe I was right about them for me.
Looking at your stats for 10-year survival, the way you read my score means one chance in 13 of recurrence within ten years. The other way around means a 1-in-4 risk, a large jump. If it was "actually" an 8, that rises to nearly 1 in 3. I wouldn't play Russian roulette with those odds. Or even casino roulette. Even if the risk of my death from recurrence is only 1%, and average survival after recurrence is 13 years, surgery was a gamble I was willing to take. Statistical averages are just that. To make an average at the craps table means someone throws a seven and someone else throws snake eyes, and others everything in between. But when you're the one in a hundred or a thousand that craps out, it's one hundred percent of you.

Anonymous said...

it is great that you are doing well. But, your example of 100% after a dice throw is wrong. Some guy just won $400 million in a lottery. So?

Cancer "survivors" will always support their decisions and providers. For prostate CA, a very common reaction is " I was 45, got screened, got treatment, now I wear diapers and need a penile implant, but I am alive. Therefore I made the right decision and the doctors saved my life." To believe otherwise would be to recognize that they and doctors made a sketchy decision and spend 20 years unnecessarily impotent and incontinent.

Henna said...

Interesting discussion. My dad is a dentist and took his time to be as informed as possible before deciding on surgery. He did not rush into it and certainly did not make a decision based on emotions. He can be maddeningly detached about medical decisions. I don't know all the details, but I do know that, like Dave, one of the factors motivating his decision for surgery was his age. Personally, I don't know that I would have made the same choice in his place.

Larry Weisenthal said...

Part 1 of 2:

Dave, Two comments.

First, I was simply going by the data about your personal case that you provided. You said that initially you had multiple needle biopsies (6 or 7 or whatever) which were positive. You said that the original Gleason score was 6 (which would be 3 + 3, in all the biopsies). You said that this was upstaged to 7 at the time of your radical prostatectomy. Based on this, it was apparent that your major pattern was three and your minor pattern was 4 (3 + 4). Now you are providing entirely different data. Why don't you fax me your pathology report (redacting your name) and give me a decent chance to analyze your case? Fax to 714-596-2110. Larry Weisenthal (you can Google me).

With regard to your tumor being in imminent danger of capsular rupture, this is poppycock, based on a Gleason 3 + 4, which is what I still believe you most likely had. What I wrote earlier is true. Danger of capsular invasion is determined by tumor biology, not by geographic proximity to capsule. Either the tumor is invasive, or it's not. If it's not invasive, it doesn't matter how big it is or how many sectors of the prostate it involves. It's a benign tumor, not a malignant tumor, and benign tumors don't need to be treated, except for symptomatic management.

With respect to the 1 in 13 possibility of cancer specific mortality after 13 years, you are again making the mistake of believing that the determining factor would be surgical (or radiotherapeutic) treatment.

No, the determining factor is biology. Did you have an invasive tumor or didn't you? By the time invasive tumors get large enough to raise the PSA level, they have quite often already metastasized. This is the "die of it" disease. Local surgery doesn't help those patients.

The clinical trials data (as I described earlier) are clear. If you've got non-invasive disease, then you don't need local treatment (precisely analogous to ductal carcinoma in situ in breast cancer). If you've got invasive disease, then local surgery (or radiation therapy) doesn't help, because what kills you is not the local tumor but the metastases.

(concluded in next installment)

- Larry Weisenthal/Huntington Beach CA

Larry Weisenthal said...

Part 2 of 2:

Expert, world class urologists at Memorial Sloan Kettering Cancer Center and similar institutions don't have the personal experience to trump the world literature, and the world literature is just as available to private practice medical oncologists like me as it is to surgical oncologists like them.

Surgeons have the mentality that, if there's a tumor, you should cut it out -- just based on logic. Surgeons swore for decades that the only way you could cure breast cancer was with the horribly mutilating radical mastectomy. But they were wrong -- proved wrong by the same sorts of clinical trials which are now defining more appropriate (and humane) management of prostate cancer. Colon surgeons used to have this elaborate "no touch technique" which was likewise consigned to the dustbin of history. Both the radical mastectomy and no touch technique were the product of "experience" and "common sense."

How on earth do they (the MSKCC urologists) have the personal experience to say that your tumor was about to invade your capsule? Do they have examples of patients who had tumors like yours whom they just followed over years to determine the natural history of the disease? This is a rhetorical question. Of course, they don't have data like that. But the world literature does have data like that.

With respect to your age, the VA study of PSA-screened patients who were diagnosed with prostate cancer and randomized between surgery and observation did not show an advantage of surgery in older men and it didn't find an advantage in younger men. If you waited until there were symptoms, you might have had many years of asymptomatic life and then, when the disease was finally diagnosed because of symptoms, you might have then been over the age of 65; you'd have had a better idea of what type of treatment you wanted to receive; and the ability to predict invasiveness (through emerging molecular technologies) would doubtless have been at a more advanced state, allowing the best choice as to most appropriate local and/or systemic therapy.

Look, I'm not trying to beat you up. You did what you did, based on the best knowledge and advice available to you at the time. But you are wrong in being a cheerleader for PSA screening, with your incorrect assertions that PSA screening saved your life, and thereby encouraging other men to subject themselves to serious morbidity for a lottery chance that they'll actually benefit from such screening, with the very high possibility that they'll suffer the morbidities.

- Larry Weisenthal/Huntington Beach CA

Larry Weisenthal said...

Hi Anon:

You say/ask:

>>But, if local treatment is mostly ineffective, then does it matter whether if the Gleason is 6 or 10 at first diagnosis absent mets?

>>In other words, what if we move questions about PSA screening one step further. Does treating Gleason 6 vs Gleason 10 save lives?<<

The following is my personal opinion, based on the literature -- not based on personal experience, which is as worthless for me as it is for any urologic oncologist -- even those at MSKCC, Johns Hopkins, MD Anderson, the NIH, the Mayo Clinic, or any other such famous institution you would care to name.

The issue is this: with rare exceptions (e.g. glioblastoma, basal cell carcinoma), cancer kills people by invading lymphatics and blood vessels and then metastasizing. Some cancers never invade and metastasize, and, therefore, don't generally kill people. Examples: in situ breast cancer (very, very common). True bronchioloalveolar cell lung cancer (not adenocarcinoma, but true, "pure" bronchioloalveolar cell carcinoma). And a great many (e.g. the majority of) prostate adenocarcinomas.

If the tumor doesn't invade, it doesn't metastasize and it doesn't kill.

So the whole ballgame is invasiveness. If you don't have an invasive tumor, you don't need radical surgery. If you have an invasive tumor, you are only helped by radical surgery if it is done before the invasion occurs.

With PSA screening, the problem is that PSA is generally only elevated at a point where invasion has already occurred, in those patients who have invasive tumors. So, if you go whacking out prostates in patients who are diagnosed by virtue of having elevated PSAs, you are generally on a fool's errand. You are mutilating scores of men who don't have invasive tumors, at no benefit. And you aren't curing most of the men who do have invasive tumors, because they have already had invasion and metastasis at the time the PSA is elevated.

Prostate cancer generally comes in two flavors: live with it and die of it.

Now, of course there are anecdotes...individual cases where patients, for example, don't have invasive disease at a certain point but who's tumors undergo a mutation which causes them to become invasive at a later point. So if you whack out those prostates before they become invasive, you can cure them. But, according to the statistics in the literature, this is lottery odds. You have to screen 1000 to 1500 patients with PSA testing to get a single lottery winner, while you subject hundreds of men to unnecessary transrectal needle biopsies and you mutilate more than 50 men unnecessarily (or, at least, unnecessarily early).

Look, if you want to be conservative, at least wait until you have symptoms. Then, if you are diagnosed with prostate cancer, you can decide whether or not surgery makes sense for you or whether you are better served by radiation or cryotherapy or microwave therapy. The overwhelming conclusions of the medical literature is that it won't make a difference if you are diagnosed by PSA or by symptoms. By delaying your decision, you'll have more data available. Better tests. Hopefully better treatments.

But you won't hear this from the surgeons. They aren't dishonest, but they are human. They believe in their craft. So do the radiologists. So do us chemotherapists. Let the buyer beware. But to beware requires knowledge. Forewarned is for armed.

- Larry Weisenthal/Huntington Beach CA

Skeptical Scalpel said...

Larry, thanks again for your most thorough review and thoughts.

Larry Weisenthal said...

Hi Dr. SS,

My comments on this thread should by no means be taken to be a denigration of the role of surgery in cancer management in general. Surgery is, far and away, obviously the most important discipline for cancer cure, in those many forms of cancer and clinical situations in which it is appropriately utilized.

My personal opinion is that surgery is actually underutilized in ovarian cancer, which tends not to invade and tends not to metastasize until very late, but kills by direct extension within the abdomen. So a two surgeon team of a gynecologic oncologist and a surgical oncologist could do long, meticulous operations with each recurrence, to grossly remove all of the disease, which tends to kill by bowel obstruction, ureteral obstruction, etc., and keep the patient going for many years, at which time, hopefully, better and better systemic treatments would be available. The problem is that these are very long, difficult operations, and the surgeons are frankly underpaid for the time they spend; so ovarian cancer tends not to get managed in this way.

Anyway, each type of cancer is unique, as is each patient's situation. Gradually, we are getting better at matching treatment to patient.

- Larry Weisenthal/Huntington Beach CA

artiger said...

Very interesting discussion on all sides. Thank you all, I've learned a good bit with this, or at least gained some new perspective.

Old Rockin' Dave said...

Further comments in reply:
A small point, but my surgery was not at MSKCC; I worked under Dr. Norton at another major institution and had my surgery at a third. My mention of him may have led you to a wrong, albeit not very relevant, conclusion.
I did not know about the upgrading of my Gleason score until a few hours before my post. Coincidentally, I had a followup visit with my urologist that afternoon. I may have given the impression that I knew about it before and this was not correct, but definitely influenced the operating urologist's decision to go ahead. My doc also knew about it but didn't tell me then. We had good reason to defer to the judgment of these two men and to accept their assessment now, too much to go into here.
You also know that cancers can spread by direct extension and by direct contact with suitable tissues. If I have seen such cases when my experience and knowledge are definitely less than yours, you must have seen them too.
Also, from the number of ovarian cases I have seen, I agree that aggressive surgery should certainly be done for it. I have seen patients whose longterm survival with other cancers was due to surgeons willing to operate over and over at each sign of recurrence; if the patient can tolerate it, it sounds like a worthwhile approach.

Todd J. Scarbrough, M.D. said...

Hey Larry. You're a med onc. I really don't talk much w/ med oncs about prostate CA; you guys only tx prostate cancer in the non-metastatic state, and so the med onc's experience treating curable prostate cancer is limited. Anyhoo, a few questions. Honestly just curious. You can infer from my questions what my answers would be.

1. Do you think that the randomized screening trials have overall shown a benefit from screening in terms of increased survivals (http://1.usa.gov/1diDafg, http://bit.ly/1diDjiC, http://bit.ly/1diDjiC)

2. Do you agree with certain literature that operating on prostate cancer patients improves survival versus watchful waiting (http://1.usa.gov/1diCS8c)

3. Do you think that for men with localized prostate cancer, the addition of androgen deprivation to local therapy improves survival (http://1.usa.gov/1diDFGc, http://1.usa.gov/1diDFGc)

4. Do you think that for men whose cancer has invaded the seminal vesicles or capsule after surgery, the addition of adjuvant radiation improves survival (http://1.usa.gov/1diE3EH)

5. For men with metastatic prostate cancer, do you think therapy (hormones, chemo, Ra-223) improves survival?

Based on the totality of the randomized evidence, do you think that 1) screening has the potential of improving survival, and that 2) therapeutic nihilism for prostate cancer is unjustified?

Todd J. Scarbrough, M.D. said...

sorry messed up a few links, and you guys only tx prostate CA in the METASTATIC setting ;)

1. screening: http://1.usa.gov/1diDkmF
3. adjuvant ADT: http://1.usa.gov/1diDM4s

Todd J. Scarbrough, M.D. said...

meant to add this also
2. surgery: http://www.nejm.org/doi/full/10.1056/NEJMoa1011967

Larry Weisenthal said...

Part 1 of 2

Hi Todd, You have the luxury of posing a number of short questions; I have the burden of providing long answers. I do have a day job; so it will take some time.

I will address the question most germane to the prior discussions on this thread:

"Based on the totality of the randomized evidence, do you think that 1) screening has the potential of improving survival, and that 2) therapeutic nihilism for prostate cancer is unjustified?"

As I tried to make clear, most prostate cancer is non-invasive (precisely analogous to in situ breast cancer) and doesn't need to be treated. It is not "therapeutic nihilism" to spare men the non-trivial side effects of unnecessary local treatment. The fact that certain local treatment modalities may be less morbid than others is no excuse for offering unnecessary treatment.

You would not propose to perform breast radiation for in situ breast cancer and you should be just as careful to avoid offering prostatic radiation for non-invasive prostate cancer (i.e. the majority of prostate cancers).

Now, what about the invasive cancers, which can and do kill people? That's where screening comes in. Yes, were there a sensitive and specific screening test which could be performed to identify invasive prostate cancer before it actually invaded and metastasized, then that would be very valuable. Unfortunately, we don't have such a test. What we have is the PSA -- and PSA suffers from the problem that, by the time it is elevated, invasive prostate cancers have already invaded and metastasized. So if you go performing surgery or radiation on prostate cancers diagnosed on the basis of PSA screening, most of which will be non-invasive tumors, you will be unnecessarily subjecting hundreds of men to transrectal needle biopsies, and you will be unnecessarily subjecting 50 men to mutilating surgery or radiation for every 1 lucky lottery winner (out of the 1000 - 1500 who are screened with PSA) who actually benefits.

Once again, to make it simple: most prostate cancers diagnosed through PSA testing are non-invasive tumors which won't ever threaten the patient's survival. Of the remainder, most are diagnosed too late, because PSA is not sufficiently sensitive and specific, and local treatment won't help.

(concluded in next message)

- Larry Weisenthal/Huntington Beach CA

Larry Weisenthal said...

Part 2 of 2

No need to make it complicated, when considering the decision to go with PSA screening or not. Listen to the American Urological Association, which is the trade organization representing the surgeons who earn a portion of their livings operating on prostate cancer:


"The greatest benefit of screening appears to be in men ages 55 to 69 years."

"For men ages 55 to 69 years the Panel recognizes that the decision to undergo PSA screening involves weighing the benefits of preventing prostate cancer mortality in 1 man for every 1,000 men screened over a decade against the known potential harms associated with screening and treatment. For this reason, the Panel strongly recommends shared decision-making for men age 55 to 69 years that are considering PSA screening, and proceeding based on a man's values and preferences."

To put it in human (i.e. my own) terms:

If I get PSA testing, there's a 1 in 5 chance that I'll get transrectal needle biopsies. If I get transrectal needle biopsies, there's a 1 in 5 chance that cancer will be diagnosed. If cancer is diagnosed, and if I'm treated with surgery or radiation, there's a 1 in 50 chance that the treatment will actually prevent my death. In other words, there's a 49 out of 50 chance that I would either have non-invasive cancer that would never need treating or else that I have invasive cancer which has already invaded and metastasized at the time of surgery.

So why on earth would I, as a functional male, ever want to get a screening PSA test?

Note that the AUA's estimate of a 1 in 1,000 benefit is generous. It's probably closer to 1 in 1,500.

- Larry Weisenthal/Huntington Beach CA

Anonymous said...

This has been a fascinating discussion, and I've appreciated that you've kept the level of dialogue civil and respectful, even though there are many hard-felt feelings about this issue.
As a gunecologist and someone who had an early INvasive breast cancer, albeit with a relatively benign oncotype, I struggle with these sorts of screening questions. Even one positive node would significantly affect long-term survival (I'm only in my early 50s) and morbidity (e.g., chemo), so it seems to me that surgery at this point was curative. But, I may be making the same fallacious assumptions, just since I'm glad to be here.
Two other points: one, if biology of the tumor is the key variable (in prostate and in breast), don't we still need to biopsy to find that out? will the PSA score tell enough in prostate? I know that imaging won't in breast) CLearly, that still leaves the problem of avoiding over-intervention in noninvasive more indolent cancers, and we need better ways to follow these. Also, we have to think, what is the baseline "5 year survival" (or 10 or 20 year) for a 56 year old man? I haven't been able to find the answer, but it clearly bears on these questions. If my 20YS with treated breast ca is 90% at 52 and my actuarial survival before that is 92%, maybe it doesn't matter. But if it's 98%, maybe it does.
Admittedly, it is impossible to be dispassionate about it when it's one's own survival, but we are scientists and we should heed our evidence. I suspect this will get easier as the molecular genetics of cancer become clearer.

Old Rockin' Dave said...

Larry, even conditionally accepting all you say, how many men, especially younger, want to live their lives with an untreated cancer hanging over their heads? For good reason, no one in medicine will ever commit themselves to an absolute answer. Who will be reassured by "To the best of our knowledge, there's only a small risk of this cancer ever making you sick or killing you?" Who will accept a care plan of "If we find something on followup, or if you develop symptoms we'll think about doing something about it. Now go home and don't worry your balding little head about it."? Not as bad as fighting in Fallujah, but still stressful, and for longer.
You say "By delaying your decision, you'll have more data available. Better tests. Hopefully better treatments." Some people would rephrase that as "Let's try kicking the can down the road".
Prostate cancer is primarily a disease of aging, and as men get older other things intervene. Travel becomes more difficult, and you probably don't know how many men I have heard from who have to travel a hundred miles or more to find a urologist who takes their insurance, or even to find one at all. If prostate cancer existed in a vacuum, it would be one thing, but what happens when concurrent health problems developing or worsening makes a man a poor risk for treatment while he's waiting around? During that wait for worsening symptoms/better treatment, what happens if he loses his spouse or other people he has depended on for support?
Of course, not screening at all would eliminate the cause of that anxiety, but on the sharp end of medical practice, how many patients ignore even the worst symptoms out of fear, ignorance, other priorities, or obstacles to obtaining care, thereby losing the window for effective treatment? No matter the numbers you provide educating the public, all too many will develop symptoms and say "Nope, never happen to me." Others will take the other kind of PSA to heart and come in at the drop of a drop in flow. Would you fail to do a PSA on someone who thought they had symptoms after reading an article? Many PSAs will still be done until something better comes along (not holding my breath) and will still pose dilemmas. People will still be treated on the basis of them with the imperfect methods we have (not holding my breath for that either).
If it's a problem, throwing statistics at it is only a part of any solution.

Anonymous said...

My understanding, as a non-oncologist, is that the question is not so much whether treating breast or prostate saves lives, but whether *screening* for them does so.

By the time a tumor gets to a detectable size, whether by mammography, or PSA, the original cell has divided many thousands of times. If the prognosis is mostly dependent on the biological propensity to invade, and not on size, does it matter if the cancer is first detected at X generation or 10X generation? I think that is the biological crux behind screening strategies.

Larry Weisenthal said...


You ask:

"if biology of the tumor is the key variable (in prostate and in breast), don't we still need to biopsy to find that out?"

To repeat the statistics:

Screen 1,000 to 1,500 men.
Find PSA elevations in 250 or so. Subject all to multiple transrectal needle biopsies. Diagnose 50 cancers.

Now, if you removed or radiated all 50 prostates, you'd save a single life. That's the best that you can achieve, because most of those tumors destined to metastasize (the invasive tumors) have already done so at the time of local treatment. So which prostates do you remove? If we had a way of identifying the one tumor which was destined to metastasize but hadn't already done so, we would then remove that prostate and only that prostate. So then the picture would be screen 1,000 - 1,500 men. Do transrectal needle biopsies on 250 of them. Diagnose 50 cancers. Remove one prostate. Cure one patient. Maybe that would then be worth it. Maybe not. Depends on the morbidity in the 250 patients who were biopsied.

But we can't identify the one tumor which was destined to metastasize, down the road, but still hadn't, at the time of the biopsy. If we don't do the 50 prostatectomies, we might miss out on curing the one patient who could be cured. So now we are back to the starting point.

Yes, I do agree with you that things will be clearer as the molecular genetics of prostate cancer become clearer. There's an average 7 year lag between PSA elevation and the development of symptoms, in those destined to develop symptoms. There's no disadvantage in waiting until symptoms develop to diagnose the tumor, based on the sum total of the literature. 7 years down the road, molecular diagnostics will be better. Hopefully treatment will also be better. - Larry Weisenthal/Huntington Beach CA

Todd J. Scarbrough, M.D. said...

Larry and DrDEG:

Larry appreciate the comments. But gosh I think attacking urologists who want to operate on prostate cancers, or neurosurgeons on brains, or medical oncologists who give chemo to Stage I young breast cancer patients (as you know the number needed to treat is high and the absolute benefit small in those cases--but I'm sure you have done it in certain scenarios), or radiation doctors who radiate... it's just unproductive. I rather choose to believe we're all good-hearted and here for the right reasons :)

Of course the PSA is just one part of the puzzle. The only thing I disagree with Larry about is his statement that "most prostate cancer is non-invasive." That is incorrect. *All* cancers (solid tumors that is) are invasive (penetrate through the basement membrane) by definition; carcinoma-in-situ is non-invasive cancer, but no one receives therapy for prostate CIS. So maybe what Larry means is "most prostate cancers are non-aggressive" perhaps. I don't know. But a Gleason's 3+3=6 adenocarcinoma is the most commonly diagnosed prostate cancer nowadays and 100% of those are "invasive." Few are aggressive though... of course the aggressiveness is a very subjective term. A Gleason 3+3=6 cancer has a ~1.25% per annum risk of prostate cancer-caused death if left untreated (http://jama.jamanetwork.com/data/Journals/JAMA/4974/JOC50024.pdf). Other prognostic features, once a cancer is diagnosed, are the PSA, the presence of perineural invasion (even Gleason 3+3=6 cancers can show perineural invasion), the stage (even Gleason 3+3=6 cancers can invade the capsule or the seminal vesicles), and the volume of disease (the ratio of positive prostate biopsies helps determine this).

The thing is, none of our prognostic metrics--even the hallowed Gleason--is perfect in predicting aggressiveness; thus we don't know which treatment is necessary versus unnecessary. This is why there's so much active work and research in my specialty to make the therapy as effective and non-morbid as possible.

Larry Weisenthal said...

Hi Todd, Thank you for making the distinction between "aggressive" and "invasive." You are correct; I was sloppy. The take home messages remain unchanged, however, as do the statistics. You screen 1000 to 1500 patients, with resultant infliction of morbidity on hundreds of patients (the transrectal needle biopsies) and serious morbidity on > 50 patients (the prostatectomy), with net benefit to only a single (1) patient!

I wasn't attacking urologists or radiotherapists. I was attacking PSA screening as a method to identify candidates for surgery or radiotherapy. And, in this case, the urologists happen to agree with me (AUA position statement previously cited).

Finally, for the record, I don't know of any US board certified medical oncologist who has been so publicly critical of his own specialty as I have been of my specialty. To my knowledge, I was the first one to bring to the attention of Medicare the practice of choosing chemotherapy on the basis of greater financial remuneration of one regimen versus another.

e.g. http://weisenthal.org/medicare_payment_for_cancer_chemotherapy.htm

With regard to treating Stage I breast cancer in young patients with adjuvant chemotherapy (where the long term effects of chemotherapy, including so-called "chemo-brain," are problematic), this is an entirely different argument and dataset, and it's never a good idea to defend a bad medical practice with comparisons to other instances of allegedly bad medical practices.

- Larry Weisenthal/Huntington Beach CA

Larry Weisenthal said...


Todd quotes a retrospective observational study:

"A Gleason 3+3=6 cancer has a ~1.25% per annum risk of prostate cancer-caused death if left untreated" (http://jama.jamanetwork.com/data/Journals/JAMA/4974/JOC50024.pdf).

As I read this statement, Todd appears to imply that, if NOT "left untreated," the mortality rate would be improved. But this does not necessarily follow and the cited study certainly doesn't provide any evidence to support the effectiveness of local therapy. The authors of the study Todd quotes concluded that local therapy (prostatectomy, etc.) of low grade prostate cancer was not justifiable on the basis of late recurrences, to wit: "The annual mortality rate from prostate cancer appears to remain stable
after 15 years from diagnosis, which does not support aggressive treatment for local-
ized low-grade prostate cancer."

To illustrate the complexity of interpreting data such as this, the fact that a given man develops a non-aggressive tumor does not provide him any immunity against developing a second, aggressive tumor years down the road. Women with cancer in one breast not uncommonly develop different forms of cancer in the second breast. If someone survives one lung cancer, they are still at risk to develop a second lung cancer. So we have no way of knowing how many very late deaths from prostate cancer are owing to some mutation in previously non-aggressive disease versus second primaries, with aggressive disease.

Presumably, one could prevent most deaths from prostate cancer by prophylactically removing everyone's prostate at age 45 or thereabouts. But we don't do this, because the morbidity to the many must be balanced against the gain to the few. This is the PSA screening controversy in a nutshell.

- Larry Weisenthal/Huntington Beach CA

Anonymous said...

Actually, I have seen several 40 year-old women undergoing prophylactic mastectomies and oophoperectomies because of their BRCA status.

My impression: how about using some common sense instead of Google searches? And that goes for the patients and their "doctors".

Skeptical Scalpel said...

The BRCA situation is quite different. The risk of invasive breast and ovarian cancer is quite high for those women.

DrDEG said...


I guess I betrayed my ignorance about what prostate biopsies can accomplish. I was assuming that there was testing that could accurately predict less-indolent tumors. For instance, a breast biopsy (which obviously is still prompted by a positive clinical finding or, more often, a screening) oncotype can be used to predict treatment (though we are still treating, just withholding more morbid treatment that might not be of significant benefit, like chemo). Currently we have no way to do that without tissue sampling (and usually a surgical specimen beyond a biopsy). I was envisioning a scenario like you described, that would enable you to biopsy many but remove fewere prostates. Of course, the issues of convincing people expectant mangement is ok remain. Cervical cancer is another example--we have almost eliminated true cervical cancers in women who are screened, but we have an identifiable premalignant lesion, and it still requires a procedure to treat. However, we have identified the high risk HPV as a marker for dysplasias we have to watch and have successfully backed off on treating though with low potential. So, it's possible sometimes to walk back the aggressiveness of treatments as more information becomes available.
Even an early invasive cancer concerns me, though, because it after all is invasive.
As Skeptical says, BRCA is a special case that should be differentiated from other types of breast CA. I can envision a day when we can perhaps screen and then sample for smaller amounts of tissue, which we can then subject to all sorts of genetic studies to determine treatment or not.
Finally, I'm still glad to have treated an early invasive cancer while the treatment had fewer downstream effects. Biased, I know, but thankful nonetheless

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