Examining The Basis For New Prostate Cancer Screening Recommendations

Image from a 3D staged biopsy - the only type that can eliminate false positives.


Many men are confused after the latest shift in advice from the U.S. Preventive Services Task Force's  2012 recommendations against prostate cancer screening.  At that time the advice was less screening, specifically via the PSA test, for men even past the age of 55, noting that the "possibility of the PSA lowering deaths from prostate cancer was very small." .  The reasons were not hard to grasp, mainly that one can get false positives which put the tested person on a track for even more invasive tests including unnecessary biopsies.  These can carry their own risks, including sepsis, impotence.

For example, the standard prostate biopsy consists of an extraction of from 10 to 20 cores of tissue.. Thus, a needle device is inserted into the rectum and each time extracts tissue from the gland after puncturing the rectal wall. The primary risk is for sepsis, which is why antibiotics like ciproflaxin must be administered in advance.

The procedure is usually done in the urologist's office without even a sedative and takes from 20 minutes to 45 minutes, depending on the number of sample cores taken. The chief side effects include: swelling and pain in prostate, possible problem urinating, and blood in urine, stools and semen. In the former two body fluids it can remain 1-2 days and in the last up to 3 months.

Even given all this, the biopsy is basically "random" and can miss up to 30 percent of cancerous lesions.  By contrast, the 3D staging biopsy entails up to 100 needle sampling insertions through the perineum to extract prostate tissue. The locations are again confirmed via trans rectal ultrasound for later mapping of all the samples to a 3D grid. The meticulous and exhaustive sampling ensures nothing is missed, hence represents the "gold standard" for prostate biopsies with up to 99 percent confidence of identifying all carcinomas.

The downside is, while vastly more accurate, it entails a far greater medical burden. Thus one must undergo a full surgery prep for general anesthesia, including being asked if you're an organ donor, and to leave an advanced medical directive .  The main risk is for hemorrhage, given the dozens of extractions.

A confirmation of lesion, however, then also is more accurately graded (by Gleason score) and can allow more choices in terms of treatment which one may not have with the standard biopsy. (For example if the standard biopsy reveals a higher Gleason score than the lesion actually merits, as I learned in my own case - after getting the 3D staging biopsy)

Now, in the new advice from the U.S. Preventive Services Task Force for men aged 55- 69, the conclusion is that the benefits of getting the test are marginally enhanced over the risks. This has been ascribed to "additional medical evidence from some clinical studies increasing the certainty about the PSA test reducing the risk of dying from prostate cancer.".   Even so, the panel's qualifying remarks noted the balance between pluses and minuses "was very close", and advised men aged 55-69 to consult their doctors in deciding whether to get the PSA.

Let's note that the statistics show that for every 1,000 men who get screened, an estimated 240 will test positive on the PSA. Some share of these - maybe 10 percent - will show false positives meaning those men will be faced with unnecessary biopsies. Those who decide to get treatment run the risk of developing impotence and incontinence as a result of surgery or radiation.

Owing to these facts,  the Task Force recommendation for those 70 and older stands by its 2012 position that "the benefits of screening do not outweigh the risks". .  The reasoning, again, is that because most prostate cancers are slowly growing, by the time one is diagnosed - say at 70 or 71 - he is still more likely to die from any other cause than cancer. (Up to 50 percent have a form of prostate cancer that doesn't spread or grow rapidly.)

In addition, an older guy getting screened sets him up for even more nasty complications, as well as costly treatments that may not be needed, and in fact are unwarranted. This is assuming such a test is positive with "high PSA" say 5.0 or 6.0.  One is then liable to be trapped in the "rabbit hole" of cancer quandaries summarized by the aspects below:

1) Cancer experts themselves can't agree on which primary treatment is best.

2) The same experts (oncologists) can't agree on which ("salvage") treatment for recurrent disease is best, or when to start it.

3) Most agree that if a guy has recurrent disease and a biopsy shows it has spread to the bones ("bone mets"), his days are basically numbered - though certain treatments (e.g. hormone) will allow some limited life extension.

Now also, once driven into the treatment domain one will have to decide how far to go, i.e. how many and what type of treatments are you willing to get in order to grab maybe ten years of life? Are you even willing to go the medical castration route?

Recall I earlier cited the Prolaris genetic test for the aggressiveness of a prostate cancer tumor,e.g.


I cited my own score of 6.6, corresponding with a 12.5 % specific risk of mortality at ten years. That translated to a 1 in 8  probability of croaking from it if I decided to do nothing.  As my oncologist (Dr. Crawford) pointed out, most guys at age 70 would make that bet.  I'm not doing it because he insists I have a better chance getting rid of the tumor completely using focal cryotherapy. But the point is for many "watchful waiting" might be an equally ok strategy.

Watchful waiting, especially if a guy is younger (say than 55)  - becomes a dicier proposition especially if the Gleason score is 6. By now most everyone has also seen or read of actor Ben Stiller's bout with prostate cancer, e.g.
http://www.cnn.com/2016/10/04/health/ben-stiller-prostate-cancer/

But what they may have ignored is how the treatments and testing can often be worse than anything else - especially if one has a slow growing cancer. The risks of further treatments include sexual impotence and incontinence  The latter means wearing diapers - as in Depends - permanently. This is also why Otis Brawley of the American Cancer Society, has warned that most men need to be very careful before stepping through that testing and treatment door. Nine times out of ten the cancer will be so slowly growing that you can do 'watchful waiting' - especially for Gleason scores of 6 or less.

But ....also nine times out of ten a guy's significant other will insist the cancer come out as in out, out, out. The idea of living with a tumor that can grow - no matter how slowly - is a non-starter.  This is why it's a good idea for men and their spouses to have "the talk" ahead of time, say before the next PSA test. Decide in advance what PSA test value or threshold sets in motion further tests, including the "free PSA" test, MRIs and prostate biopsies (including MRI fusion biopsy.)

The Good News: I'm A "Perfect Candidate" For Focal Cryo Treatment

The meeting with Dr. E. David Crawford earlier this week was concerned with the outcome of the 3D staging biopsy done some two plus weeks ago. To say it went well would be an understatement, especially after he displayed the 3D grid of the mapped prostate on his computer.

He pointed to one localized region, roughly 5-6 mm in diameter, where all the cancer was confined. There were no other lesions or regions, and that assurance is the primary benefit of having the much more invasive 3D biopsy. No such assurances exist for those who get regular prostate biopsies, including the highly touted MRI fusion form (which I also had).

Recall that biopsy mistakenly identified separate cores, e.g.


And the pathology report showed a Gleason 7 score in one region (3 + 4) with 63 percent of the cells assigned malignant status and also with "perineural invasion". Thus, I beheld the summary of diagnostic information as shown:



However, none of that was confirmed in the 3D staging biopsy. Indeed, there was no evidence of any perineural invasion, as the localized lesion was situated not only apart from the rectal wall but also from the urethra. In addition, the maximum Gleason score pair for the sole cancerous region was 3 + 3, not 3 + 4.  

When Janice asked what could account for the difference in Gleason score, as well as the reduction of multiple lesions to just one, Dr. Crawford said "the radiation treatment he had four years earlier". Basically, that high dose brachytherapy treatment - leaving loads of "scar tissue" - left the histology analysis a mess, and unreliable. That pathology report was basically useless, at least in terms of moving forward. Had I therefore not had the 3D biopsy I likely would have opted for a follow-up treatment that was inappropriate.

Dr. Crawford assured me there was no rush to get the treatment done, and in that case I've postponed it until later in the year, after we take a holiday in Barbados.  In any case, as I told him, I was still contending with residual urinary burning as well as urgency, which he agreed was because of the Foley catheter. Again, it had been in barely two days. 

When I asked him how long it would need to be inserted after the focal cryo, he said it "varied" but steered clear of his original claim of "one day" (which his RN vigorously disputed when I spoke with her after the biopsy)  He agreed the most likely interval was 2-4 days, which pretty well conforms with the 3-5 days cited on the UC site. But I am hoping given the localized tumor and placement, it can maybe come out in 2-3 days. 

We will see.   For now, I am simply enjoying the good vibes of being the "perfect candidate" for this focal cryotherapy treatment.  I have asked for the copy of the 3D grid map with the lesion identified, and when I receive it from UC Health I will post it as an update on this post.


See also:


https://www.youtube.com/watch?v=-OnqA-mJDWg


And:


http://www.edavidcrawford.com/targeted-prostate-cancer-treatment

3D Staging Prostate Biopsy Unlikely To Come Into General Use - My Account

Image of a 3D reconstruction- with grids superimposed-- after 3D Staging Biopsy. Note the prostate (in red), urethra (in green) and the exact location of areas of cancer (in mud yellow). 


The advantages of the 3D staging biopsy for prostate cancer which I just had two days ago, are well known and explicated wonderfully on Dr. E. David Crawford's University of Colorado site. We are informed, for example, that with this 3D rendition many more lesions, prostate cancer tumors can now be identified because the technique is much more thorough. As Dr. Crawford has noted, from 10-30 percent of prostate cancers are missed even in the MRI fusion biopsy.

In other words, given the much higher accuracy the 3D Prostate biopsy is now the "gold standard" for PCa diagnosis. But that standard doesn't mean many more men will choose it.  We need to look at why this is so.

The standard prostate biopsy is more or less an "in and out" procedure, done rectally with the accompaniment of an ultrasound to provide location data for the prostate sampling. This may be from 10 to 20 cores. Thus, a needle sample device is inserted into the rectum and each time extracts tissue from the gland after puncturing the rectal wall. Primary risk is for sepsis, which is why antibiotics like ciproflaxin must be administered in advance.

The procedure is usually done in the urologist's office without even a sedative and takes from 20 minutes to 45 minutes, depending on the number of sample cores taken. The chief side effects include: swelling and pain in prostate, possible problem urinating, and blood in urine, stools and semen. In the former two body fluids it can remain 1-2 days and in the last up to 3 months.

The 3D staging biopsy by contrast is an entirely different animal. While described as an "outpatient" procedure, you are actually administered general anesthesia because the technique is much more invasive and entails up to 100 needle sampling insertions through the perineum to extract prostate tissue. The locations are again confirmed via trans rectal ultrasound for later mapping of all the samples to a 3D grid. The samplings are taken approximately 5mm apart. In my case a total of 45 were taken, fewer than originally projected (60).

Of course, before getting it done you are undergoing a full surgery prep, including being asked if you're an organ donor, and to leave an advanced medical directive (or living will) in case the surgery or anesthesia goes awry - or you hemorrhage. Also Janice had to be there to provide durable power of attorney and medical power of attorney in the event I was left unable to render decisions, directions for my own care.

In the pre-op setting you also discuss with the anesthesiologist any allergies, and note if you are sensitive to meds (as I am.) By the time you are being wheeled into the OR you are already half out of it from the mix of sedatives, painkillers including fentanyl.

Once in the OR you must move yourself from the gurney to the operating table where the sampling is done. I don't believe I'd completed the transition more than a minute before I was knocked out.   (Just before I was asked by a urology resident if I wanted a transfusion in case of hemorrhage, and I gave my blood type).

I awakened in the PACU or Post-Anesthesia Care Unit, to the soft voice of a beautiful nursing grad student, "Rachel", who asked the usual questions: Where are you? What is your name? What is your date of birth? What year is it? Etc. All this is done to ensure you are all there.

She then questioned me about the pain, where it hurt and the nature. I told her the worst aspect was a burning sensation all through the urethra, from the catheter. (I ended up opting for a Foley catheter, as opposed to supra-pubic on the advice of a urology resident, "Tim".).

She immediately brought me three meds to take with water, one of which was specifically to reduce the burning sensation that had become almost unbearable.

After giving me the meds, she brought me a few light Jello snacks. This time (unlike my gall bladder removal in May) there was no nausea at all so the anesthesiologist hit just the right mix.

Janice by now had also come up, after tracking my various locations using a "patient tracker" - coded by color to follow my progress. Once she arrived, Rachel and another student RN ("Callie")  showed her how to change the catheter bags, and also go from the usual (day time) leg bag to the much larger night bag.

Let me say right off the bat that having a Foley catheter in place is no ball of fun, and ranks maybe up there with a root canal - or two.  I had to wear the damned thing for two days before Dr. Crawford's RN gave the ok to take it out.   She emphasized it was foolhardy to do so too early because then "you could be in a real world of hurt". That refers to all the ancillary tissues swelling up preventing urination, which earns you a trip to the ER. 

So now, with it out I am still recovering and will get the results of the biopsy in 5 days or so.

Having had the normal biopsies and this one I can agree right now with what a paper dealing with it noted, that in general most men would not opt for it given the greater "medical burden" - that entails more invasive procedure - as I described - as well as more side effects, bleeding from rectum, penis, etc. and pain as well as having to wear a urinary catheter.

Most men, despite the touted accuracy of results (which isn't in dispute),  will simply not opt for this advanced biopsy unless they are looking for a specific treatment option (e.g. focal cryo-ablation) for which it is required.

Anyway, recovering now, and thankfully with no catheter. I am just waiting for further word on whether I am a candidate for the focal cryo. I will have to meet with Dr. Crawford again in 2 weeks.

See also:


http://www.edavidcrawford.com/video-gallery

Update:

Yesterday (1/24) I received word from UC Health that the biopsy came results came out favorably for further treatment. 5 of 45 cores showed cancer but no scores higher than Gleason 3 + 3. So I am cleared to schedule treatment in about two months.

Biopsy Result Shows Writing On The Wall - Maybe Limited Time To Act

Horizontal -spatial view showing distribution of cancer regions and percentage of cells deemed malignant

The grim-faced urologist entered the patient consultation room late yesterday morning as wifey and I stood up to greet him. Since I already suspected the worst (from an earlier telephone call) I wasn't totally shocked into insensibility when he handed me the summary sheet for the recent MRI fusion biopsy, e.g.

http://brane-space.blogspot.com/2016/09/what-i-got-wrong-about-my-mri-fusion.html

The worst part of the damned pathology report was the Gleason 7 score in one region (3 + 4) with 63 percent of the cells assigned malignant status. My temptation was to try to emphasize the benign regions and the lower (Gleason 6, or 3 + 3) score areas, e.g.

But the urologist wasn't sharing any confidence for non-action. It was clear from these results as well as the associated Partin Table*,


 I had little choice other than to act, or face a possible metastasis of the (currently) confined cancer in as little as 5-6 months. But to establish whether I had even that much time to act, the urologist suggested getting a genetic marker test, made on the biopsy cells - called Prolaris.  This test is designed to indicate whether the cells in that Gleason 7 region are very aggressive, or much less so. If the former, I will have to act much more rapidly.

When I asked how much time I'd have if I did nothing, he hedged, conceding no test could be a crystal ball. However, wifey, who worked for decades in the fields of radiotherapy treatment as well as software testing, warned me the last stages of the disease could be agonizing with bowel and bladder problems, bone fractures and pain that would be enough to make the strongest guy cry unless he was on a diet of opioid pain killers. (Which I hate, since I don't like taking anything more potent than a baby aspirin). So it appeared even Janice was taking the doc's side that I had no choice other than to treat the damned thing.

After fifteen minutes of discussing treatment options, side effects, the choices came down to two: 1) focal cryotherapy, or 2) salvage brachytherapy.  (1) is the "ice ball" treatment that is shown in two videos in the link above. (2) represents a repeat of the treatment I had in San Francisco four years ago but now done in two administrations, at much higher doses (36 Gy a week apart).

The urologist affirmed that he leaned more to (1) given my previous experience with brachy indicated the cancer was resistant to this treatment. That basically meant I might be "nuking" my prostate - including urethra and bowel, for nothing. (But I am still waiting for a full brochure or document discussing the full salvage treatment from UCSF).

I said earlier, with much bravado, I was prepared to do nothing. But that was delivered with the understanding (or assumption) I'd have maybe 7 quality years left. However, if doing nothing means dying in 1-2 years then it becomes a no go, a non option. I might be ready to toss in the towel at some point, but not that early.

If the focal cryotherapy is chosen we have in mind an expert in Denver, Dr. David Crawford, who is also at the forefront of 3D staged biopsy. That will necessitate a meeting with him to see if I qualify and also (likely) another 3D biopsy with full mapping - meaning that he'd take up to 150 core samples while I am knocked out under general anesthesia. Then, a month or so later I'd have the procedure done and stay over in a hotel until the Foley catheter can be removed (hopefully in under a week).

For now it's a watching and waiting game and the pathology slides also have to be reviewed by Dr. Hsu of UCSF. I am hoping on his review he will find that the Gleason 7 region is really a 6 and there are more benign areas than malignant.

But....that may be just wishful thinking.

* Partin Table:

A probability table showing outcomes expected just prior to treatment, assuming it is done in a reasonable time. A table shows the probabilities of the cancer remaining contained in the gland or getting out ("extraprostatic extension") including getting into lymph nodes. Bracketed values shown with it give the 95% confidence values.

See also (for more information on the 3D Staging biopsy and Focal Treatment):

http://www.edavidcrawford.com/targeted-prostate-cancer-treatment