Prostate cancer in men with advanced bladder cancer

A new article in the journal Urologic Oncology has highlighted an association between the occurrence of advanced bladder cancer and the related finding of prostate cancer among such patients who have their prostate removed along with their bladder at the time of initial surgery  for the bladder cancer (i.e., a radical cystoprostatectomy).

Now in all honesty this doesn’t exactly come as a surprise to your sitemaster. Most of the men being given the radical cystoprostatectomies in this study were > 60 years of age, and the average age of the men found to have cancer in their prostates as well as in their bladders was almost 70 years. Men of that age have a very high probability ( of the order of 70 percent) of having at least some amount of cancer in their prostate.

The abstract of this paper by Heidegger et al. is available on line, as is a commentary on the Renal & Urology News web site.

What Heiddegger and her colleagues did was conduct a retrospective analysis of data from a cohort of 213 patients diagnosed with advanced forms of bladder cancer, all of whom were treated by surgical removal of their bladders (a radical cystectomy) and most of whom seem to have also had their prostate removed at the same time as an integral part of the procedure (a radical cystoprostatectomy).

The research team found that

  • Just over half the patients (113/213 or 53.1 percent) had some prostate cancer in the surgical specimen on pathological examination.
  • 59/113 patients with prostate cancer (27.7 percent of all 213 patients) had a Gleason score of 7 or higher.
  • The patients׳ ages, PSA levels, and percent free PSA levels were predictive for prostate cancer.
  • Stage pT3 or higher bladder cancer was found in 63.7 percent of the patients who also had prostate cancer.
  • Among the 113 patients who did have prostate cancer as well as their bladder cancer,
    • 32/113 (28.3 percent) had a PSA-based biochemical recurrence (PSA  ≥ 0.2 ng/ml).
    • 28/32 who had a biochemical recurrence (24.8 percent of all 113 patients) had a Gleason score of 7 or higher
    • 9/32 who had a biochemical recurrence (8.0 percent of all 113 patients) died of prostate cancer rather than bladder cancer.

So one way to look at these data is to say that out of 213 men with advanced bladder cancer in the cohort evaluated by Heiddiger et al., 28 or 13 percent also had an intermediate or high-risk (but non-metastatic) form of prostate cancer at the time of treatment for their bladder cancer and 9 or 4.2 percent actually died of prostate cancer.

Heiddigger et al. conclude that prostate cancer

is occurring in > 50 percent of [radical cystectomy] specimens with a significant proportion having characteristics … of clinically relevant disease. Adverse bladder histology is a risk factor for both [prostate cancer] and biochemical PSA recurrence. Follow-up analyses after [radical cystectomy] should include PSA measurements also in low-risk [prostate cancer] as a considerable number of patients develop biochemical recurrence and metastases from [prostate cancer] partly ending up with death related to [prostate cancer] in patients suffering from [bladder cancer].

A rather different conclusion might be this one:

A finding of concomitant prostate cancer is probably not uncommon among older men being given a radical cystoprostatectomy as one component of their treatment for advanced bladder cancer. Pathological evaluation of the prostate as well as the bladder tissue after a radical cyctoprostatectomy is wise. In patients exhibiting cancerous prostate as well as bladder cancer tissues, appropriate protocols need to be followed to monitor risk for progressive prostate cancer — most especially among those men with elevated PSA levels and/or Gleason scores of 7 or higher.

One of the problems with the data from Heiddiger et al.’s retrospective cohort study is that we have no idea whether any of the patients in this study had had any evaluation for risk of prostate cancer prior to their treatment for advanced bladder cancer. The very fact that they were being treated for advanced bladder cancer could arguably suggest that it was unlikely that these men had ever been evaluated for risk of prostate cancer, and so their risk for prostate cancer was inevitably high based on their ages and the lack of any prior testing.

Another of the problems with this paper is the way the authors focus on giving the highest possible percentages for risk by focusing on percentages of patients who are clearly at higher risk for prostate cancer problems as opposed to on the percentages in the group as a whole.

Is there a risk that men of 60 or older who are given a radical cystoprostatectomy to treat advanced bladder cancer may also have high-risk prostate cancer? Yes, of course there is, especially if they haven’t been having PSA tests to assess risk for prostate cancer. And based on this patient cohort some 4 percent of those patients may actually die from metastatic prostate cancer as opposed to their bladder cancer.

7 Responses

  1. I am concerned. 28 patients had prostate cancer and a biochemical recurrence. 9/28 of the patients died of prostate cancer. I am concerned about the treatment for biochemical recurrence after radical prostatectomy. In a recent study of about 2000 patients, risk of a second biochemical recurrence was evaluated in relation to timing of the salvage treatment. The risk of a second biochemical recurrence was lowest if salvage irradiation was started while PSA was 0.1, and risk of second biochemical recurrence increased as PSA at salvage treatment was higher. A commentary argued for concern about PSA at start of salvage treatment. Here obviously risk of a second biochemical recurrence was more than 35 percent. That suggests that salvage treatment was given (if given) at a PSA level clearly higher than that recommended today. The study is interesting because many other studies of salvage treatment does not detail the clinical course after second biochemical recurrence. In this study mortality, for patients with a second biochemical recurrence must have been very high.

  2. Dear Finn:

    I really don’t think that you should be making judgements about risk for recurrence of prostate cancer based on data from this series of patients. They are a long way from being “standard” prostate cancer patients and all the data we have is from a retrospective analysis. We have absolutely no how well they were monitored or managed at the time of their actual treatment (for bladder cancer as the first priority).

    Risk for a second biochemical recurrence after surgery and salvage radiation therapy is relatively low today except inpatients with highly aggressive forms of prostate cancer, and it is customary to monitor patients today using ultrasensitive PSA testing as opposed to standard PSA testing for exactly tghe reason you describe — so that salvage radiation therapy can be given much earlier than used to be customary.

  3. Great information! Thanks for sharing.

  4. You may be right that in a good oncology service, deaths of prostate cancer could be less than it was for the patients who had biochemical recurrence in the present series. However, these patients were followed by physicians devoted for the case of patients with urologic oncology. So the data suggest that present guidelines for patients with biochemical recurrence was not followed.

    I live in Denmark. We had a national study of salvage radiotherapy. It was published by Ervandian et al. Here initially, salvage radiotherapy was given with ADT for all patients, later SRT was given without ADT. The outcome was best during the first period for the high-risk patients. I was concerned about how patients are treated in Denmark today. So I wrote a letter to a leading Danish professor of what is going on today. Denmark is supposed to follow guidelines from the European Association of Urologists. The letter was sent at the beginning of December but so far I have had no reply.

    In Denmark, PSA is given with one decimal, here as a patient can go to Austria and see the same analyte measured and reported with two decimals. Some Danish physicians will only react for changes of PSA of 2 or more.

    So I feel the concern is relevant. It is not how good it can be for the best centers but how it is in other units.

    I worked as consultant in internal medicine in a small provincial hospital in Norway and referred patients with large prostate glands, slight urinary retention, and PSA levels of 70 for evaluation of the risk of cancer to the local urologist. He put in writing for one of my referred patients — why should he be bothered with taking care of the patients when it was obvious the patient most likely had prostatitis? (Sigh! Patient with no pain, no fever and so on.) …

  5. Dear Finn:

    Thank you for your clarifications.

    I am not, for one moment, suggesting that all prostate cancer patients who need salvage therapy get the highest quality of care. They don’t. There are a lot of poor physicians out there who don’t keep up to date with the relevant data and who seem to be seriously lacking in their degree of “care” about and for their patients.

    My concern with the series of patients in the article discussed above, however, would be that the men who did have prostate cancer and who went on to die of it may well have had micrometastatic prostate cancer by the time it was recognized that they had prostate cancer or even their bladder cancer at all. If that was the case, salvage radiation therapy was probably doomed to failure in any case, but we don’t have enough data to be able to assess the situation with accuracy.

  6. I agree that with EBRT even with wide target volume as not covering micrometastases. However, at present we might use theranostic treatment with for instance lutetium-177 PSMA-617 for dealing with micrometastases. That treatment is at present experimental but several reviews have opened for new developments.

    The treatment demands high technology and it might not be better than adherence to present guidelines where salvage radiotherapy may reduce risk of a second biochemical recurrence to 10%.
    I am very optimistic that we have the tools today to avoid most of the previous deaths from biochemical recurrence and that is why I commented on the study of prostatecystectomy.

    For the pessimist, micrometastases is often given as the explanation for the failures. They will call my thoughts as “very controversial”, “not based on evidence-based medicine”. For the optimist, adherence to guidelines, use of supersensitive PSA determinations, multidisciplinary teams, and an open eye for new developments may bring a better future.

    Hopefully, there will be a constructive dialogue between the pessimists and the optimists and a will to go from discussions to investigations.

    A cancer hospital in Australia got a million dollar grant for further investigations of theranostic therapy of prostate cancer, and it is available in at least six units in Germany. But still it has to compete with best use of previous available approaches.

  7. Dear Finn:

    I think a very great deal depends on the precise biological/genetic nature of the specific prostate cancer. There are some forms of very aggressive prostate cancer that simply don’t seem to be responsive to any type of local therapy. My suspicion is that those cancers have probably already micrometastasized to bone marrow by the time they get diagnosed, and even things like Lu-177 may not be able to deal well with cancers like that.

    On the other hand, we are making great progress (albeit slowly) with improving our ability to treat most clinically significant, localized prostate cancers — even when they have micrometastasized to the lymph nodes and other parts of the pelvis.

    I have been doing this for nearly 30 years now …. The opportunities are radically different from the very crude forms of radiation therapy and early forms of hormone therapy that were pretty much all that was available back then outside a very small number of institutions.

    As a physician, you will inherently understand why physicians are often slow to adopt the very newest technologies. That’s not always a good thing, but sometimes it’s a very good thing indeed (when we find out the unexpected side effects of what looked like a good thing at first).

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