Outcomes of 55 men who had prophylactic RALPs for suspicion of unproven prostate cancer

Over the years, we have been asked several times whether there is a role for any type of  immediate treatment in men with a high level of concern for their risk of prostate cancer — despite a negative finding on prostate biopsy.

We have always answered this question by saying two things:

  • We knew of very small numbers of patients with a serious family history of prostate cancer who had been treated in this way by small numbers of surgeons.
  • We were also aware of published data from a small series of patients treated surgically for severe, chronic prostatis, whose symptoms appeared to have been largely resolved by their treatment at 1 year of follow-up.

Now we have a report from Taiwan that gives a retrospective analysis of all the available data from a series of 55 men, most of whom were negative for prostate cancer on biopsy, but who were sufficiently concerned about their risk that they went ahead and had prophylactic robot-assisted laparoscopic surgery (RALP) anyway.

The paper by Ou et al. has just been published in Anticancer Research and marks an interesting step in the evolution of the discussion about when and in whom such prophylactic treatment is either appropriate or necessary. And we should be clear that we have read the entire text of this paper prior to commenting.

Ou and his colleagues clearly have significant experience in the conduct of RALP. The 55 patients in question come from a total series of 1,060 patients, all operated on by the same surgeon (Dr. Ou) between 2005 and 2015. The first of the 55 men to receive a prophylactic, nerve-sparing RALP was operated on in 2012 after Dr. Ou had already conducted 365 prior RALPs.

In every case, there was also, clearly, a thoughtful decision process about the surgery:

  • The majority of the patients had had a negative, TRUS-guided prostate biopsy (see below).
  • All patients were followed for a minimum of 6 months after that initial negative biopsy and before any decision about the surgery.
  • Follow-up in the period prior to surgery included repeat biopsies, MRI studies, and repeat PSA testing.
  • Patients and their family members were invited to a group education course conducted by the lead author where they were clearly advised about the potential side effects and complications of RALP.
  • The research team seems to have gone out of their way to ensure that all patients and relevant family members were fully aware of the possibility that the patient might well be found to have no prostate cancer in the pathological specimen post-surgery.

In addition, Ou and his colleagues ensured that they collected an enormous amount of detailed data on these patients, their actual operations, and their outcomes. They also carefully point out that a limitation of their study is that all data were collected prospectively, but analyzed retrospectively.

So let’s start with the presurgical data:

  • 13/55 men (including two physicians) had refused to have a biopsy at all.
  • 42/55 men had between one and four biopsies prior to their surgery.
  • 41/55 men had agreed to have a 3-T, multiparametric MRI scan (which they had to pay for themselves; this was not a funded clinical trial) evaluated according to PI-RADs criteria.
  • The patients’ average (mean) PSA level prior to surgery was 16 ± 2 ng/ml.
  • Other data collected included the patients’ ages, BMIs, PSA levels, PSA densities, symptom and quality of life scores, DRE findings, etc.

All such data are carefully reported by Ou et al., along with such things as length of time of surgery, blood loss during surgery, and other factors.

So what were the immediate outcomes?

  • All patients were successfully treated with a bilateral nerve-sparing procedure.
  • Two patients had intraoperative complications (one of which involved a minor bladder injury and repair).
  • 22/55 patients (40 percent) were found to have prostate cancer (including 5/13 patients who had refused to have a biopsy at all).
  • 18/55 patients (33 percent) were found to have other prostate abnormalities such as prostatic intraepethelial neoplasia (PIN) or atypical small acinar proliferation (ASAP)
  • 15/55 patients (27 percent) had benign disease (inclusive of men with nodular hyperplasia and/or inflammation of the prostate).

The paper also provides detailed information on the pathological findings for the 22 patients who were found to have prostate cancer, as follows:

  • Pathogical staging included T2a (n = 6), T2b (n = 7), T2c (n = 2), T3a (n = 6), and T3b (n = 1).
  • Gleason scores included Gleason 5 (n = 3), Gleason 6 (n = 9), Gleason 7 (n = 7), and Gleason 8 (n = 3).
  • 4/22 patients (18 percent) had positive surgical margins.
  • 5/22 patients (23 percent) had perineural invasion.
  • No patients had lymph-node-positive disease.

In addition, in looking at the entire set of 55 patients:

  • The post-surgical continence rate was 100 percent.
  • Average (mean) time to recovery of continence was 11 days (range 0 to 28 days) after removal of the urinary catheter.
  • Other data show clear improvements, on average, in the patients’ urinary function and quality of life scores.

No data are provided about the patients’ sexual function before or after their surgeries in the original paper, but please see the additional note at the foot of this page.

Dr Ou and his colleagues conclude that:

Prophylactic [RALP] with bilateral [neurovascular bundle] preservation is safe for patients with suspicion of [prostate cancer] when peformed by experienced surgeons. Postoperatively, [RALP] improves urinary function and [quality of life].

The “New” Prostate Cancer InfoLink does not feel it is appropriate for us to comment on the question of whether patients should or should not actually consider prophylactic radical prostatectomy (or any other form of prophylactic treatment) for unproven prostate cancer. This is a very highly personal decision. As the authors note, the first patient on whom they carried out such a procedure was a man with a significant familial history of prostate cancer.

Conversely, however, Ou and his calleagues have now given us some very clear documentation of how they went about the conduct of such procedures; the outcomes that any such patients might reasonably be able to expect at a suitably experienced surgical center; and the ways in which they documented the pre-surgical and post-surgical evaluation of such patients. For this, future potential patient (and the surgeons who may be willing to conduct such procedures) should be extremely grateful.

And one last thought. If any patient is considering the idea of having a prophylactic radical prostatectomy (or any other form of prophylactic treatment) for suspicion of an unproven prostate cancer, he would be wise to make very sure that he is talking about this with a treatment team that is at least as experienced as the one reporting these data, and which takes the same level of care to ensure a complete understanding — on the part of the patient and his family — of the risks involved.

Editorial notes: The “New” Prostate Cancer InfoLink thanks Dr. Yen-Chuan Ou of the National Yang-Ming University in Taipei, Taiwan, for promptly providing us with a copy of the full text of this important paper.

The lead author of the paper has also advised us — in a separate note — that, at 12 months after surgery, among 36 of the 55 patients who were potent prior to their surgery, potency (i.e., an erection sufficient for intercourse) was achieved by 32/36 men (88.9 percent) either with (n = 9) or without (n = 27) the use of phosphodiesterase type-5 inhibitors (i.e., drugs like Viagra and Cialis). These data are based on patient assessments using the International Index of Erectile Function (IIEF) scale, both preoperatively and postoperatively.

11 Responses

  1. In 2016 I cannot imagine making that decision.

    “I might get hit by a car tomorrow. I better kill myself now.”

    Mind boggling.

  2. Dear Walt:

    It might not be so mind-boggling if you imagined yourself to be a 45-year-old man whose PSA was rising and whose father, grandfather, and an uncle had all died of metastatic prostate cancer in their 60s. Try reading this article.

  3. With the science available in 2016, it’s more than mind boggling. but I’ll leave it there. :-)

  4. I wonder what the PI-RADs were on the patients that had MRIs.

  5. Mark: Here you go:

    — 41 men had an MRI.
    — In the men who had an MRI and were actually found to have prostate cancer, 5/17 (29%) had a PI-RADs of 2-3 and 12/17 (71%) had a PI-RADs of 4-5.
    — In the men who had an MRI and were found to have PIN/ASAP, 6/14 (43%) had a PI-RADs of 2-3 and 8/14 (57.1%) had a PI-RADs of 4-5.
    — In the men who had an MRI and were found to have benign disease, 6/10 (60%) had a PI-RADs of 2-3 and 4/10 (40%) had a PI-RADS of 4-5.

    Remember that the men who were found to have prostate cancer included men with distinctly low-risk disease that might easily have shown up as PI-RADs 2-3. What is more worrisome are the relatively high PI-RADs scores in a significant number of the men who turned out to have PIN/ASAP or benign disease

  6. I agree with Walt. If suspicion remains after a first negative biopsy, there are several steps that can be taken before maiming a perfectly healthy man. Those steps include biochemical tests (PHI, 4Kscore, PCA3, Oncotype Dx, Prolaris, etc.), mpMRI-targeted biopsies, and transperineal template-mapping biopsies. Some early results are showing that some of the new PET scans may be useful too in the future. Also, attempts should be made to identify benign sources of elevated PSA. We have some pretty decent tools in our diagnostic armamentarium that ought to be rolled out before radical therapy is used.

  7. Dear Allen:

    On “rational” grounds both you and Walt are correct. However, many people do not think about these things “rationally” at all. They are driven by the experiences of those close to them and by other “irrational” factors that seem perfectly rational to them.

    The good thing about this important paper is that it gives us meaningful outcomes data that will help in having conversations with these patients. The fact that you and Walt wouldn’t even consider such action is actually a long way from the whole point.

  8. I’ve dealt with one patient who had a prophylactic prostatectomy (they found a small amount of Gleason 6 and a few patients who, based on positive biopsies, tragically had prostatectomies where no cancer was found. I spend a lot of time talking patients down, and getting them to slow down the decision-making process. So often, their reactions are based on their fear of the word cancer and what it has meant to others in their family. But I don’t get to a lot of patients until afterwards — they always see a urologist first. A doctor has a duty to do no harm, even if that is what the patient wants. Perhaps a better way to deal with a fearful patient is to bring in a counselor, send him to a support group, give him a sedative to help him sleep better … whatever is needed to slow down and cool off what is often a very heated emotional process. It would help a lot if doctors assisted by not accepting an immediate decision, let alone pressuring the patient to make one, as I have seen them do.

  9. Again … I am not disagreeing with you … But it is very clear from what was happening with the patients Dr. Ou and his colleagues were dealing with that they did slow down the decision process; they did seek to carry out multiple other tests; and yet the patients still wanted treatment.

    I am not trying to justify anyone’s behaviors here. And my knowledge of the cultural issues related to a diagnosis of cancer in Taiwan is absolute zero. My only point is that “logic” does not always prevail … in all sorts of circumstances. This is often despite the best efforts of the physician. (See the other article that I gave Walt a link to, which happens to be a case I had discussed in detail with the physician in question several years ago, and long before that article was published.)

  10. I know you are not disagreeing – you are probably the biggest advocate for active surveillance around – and I mean that as a great compliment. I read the link just now. The problem with media pieces like that Esquire story is the reader may take the anecdote to be more than an anecdote, and the fact that all was well in the end with that one man to be an indication that all will turn out well if he does it too. I would note that current AUA guidelines advocate a repeat biopsy of men with atypia within 6 months. (I also raised an eyebrow over the morcellation of the prostate.) I am very sceptical of the 100% continence they quote in the Taiwanese study. Will the facts they gathered aid in similar discussions in the future, as you suggest? I doubt it. As you said, these men weren’t making fully rational decisions, and throwing even more facts at them just isn’t likely to get processed.

    In another link you posted today to an excellent article about doctor/patient communications there is a cartoon that says it all. “cancer blah blah blah cancer blah blah blah etc.” It isn’t just the jargon (which is what the article talks about). Patients get emotionally hung up on the word cancer and often process little else other than that word. The challenge for the doctor is to find a way of changing that communication dynamic. Time, peer support, and relaxation techniques (I practice mindfulness) are some of the resources the clinician can use to support the patient. There will always be some patients that no intervention will help with, who will get on a plane to Mexico and drink the laetrile, but I see ethical issues in doctors treating patients for diseases they don’t have when the side effects can be so serious.

  11. With regard to the “morcellation” of the prostate, you need to understand that this was among the earliest laparoscopic procedures done in America to remove a prostate. Even the pioneers were still learning.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: