Survival times among men with biochemically recurrent prostate cancer


It would hardly come as a shock to most experienced prostate cancer advocates and patients to learn that there is an association between survival time and the aggressiveness of a patient’s cancer at the time of diagnosis if that cancer progresses.

A report in Renal & Urology News has discussed two poster presentations from the Genitourinary Cancer Symposium earlier in the year that relate to this concept.

In the poster by Akamatsu et al., the authors looked at the survival times of three groups of patients who were diagnosed with or went on to have metastatic prostate cancer:

  • Patients in Group A (n = 35) were all initially diagnosed with metastatic disease or metastatic disease was diagnosed within 3 months of their initial diagnosis.
  • Patients in Group B (n = 26) were all metastasis free at diagnosis, but metastasis was identified > 6 months before they became castration resistant.
  • Patients in Group C (n = 31) all had metastasis identified < 6 months before they became castration resistant or after the onset of castration resistance.

Analysis of patient characteristics and patient survival data showed that:

  • 85 and 84 percent of patients in Groups B and C had received some type of local therapy (i.e., surgery and/or radiation) and the types of local therapy were similar between the two groups.
  • Treatments administered to patients in all three groups after the onset of castration resistance included abiraterone acetate, enzalutamide, and docetaxel, and use of these agents were similar between the three groups.
  • Among patients in Group A
    • Median follow-up was 2.2 years.
    • Median time to onset of castration-resistance post-diagnosis was 1.4 years.
    • Median overall survival post-diagnosis was 3.7 years.
  • Among patients in Group B
    • Median follow-up was 9.6 years.
    • Mean time to PSA recurrence after initial therapy post-diagnosis was 3.5 years.
    • Median time to onset of metastasis post-diagnosis was 4.4 years.
    • Median time to onset of castration-resistance post-diagnosis was 6.2 years.
    • Median overall survival post-diagnosis was 12.3 years.
  • Among patients in Group C
    • Median follow-up was 11.8 years.
    • Mean time to PSA recurrence after initial therapy post-diagnosis was 2.2 years.
    • Median time to onset of metastasis post-diagnosis was 11.4 years.
    • Median time to onset of castration-resistance post-diagnosis was 8.6 years.
    • Median overall survival post-diagnosis was 15.8 years.

These data demonstrate, unsurprisingly, that (a) men who are initially diagnosed with metastatic disease (Group A) are at very high risk for a short period of overall survival and (b) that the onset of metastasis some time before the onset of castration-resistance (Group B) is associated with a somewhat shorter period of overall survival than the onset of metastasis shortly before, or after, the onset of castration resistance (Group C).

In the second poster, presented by Valenca et al., the authors set out to see if they could determine whether there was a meaningful correlation between time to metastasis (TTM) and overall survival (OS) such that TTM could be used as a surrogate endpoint for OS in clinical trials of treatments  for men receiving treatment for biochemical recurrence after first- and second-line therapies.

The authors based their analysis on a cohort of 415 patients with non-metastatic but biochemically recurrent disease, all of whom had been treated with androgen deprivation therapy (ADT) at the Dana-Farber Cancer Center (but over what time frame is not specified).

Here are the core results of this study:

  • Median overall follow-up was 6.4 years.
  • Among 398 patients followed from initiation of ADT (Group X)
    • 180/398 (45 percent) developed metastasis.
    • Median TTM was 6.25 years.
    • 152/398 (38 percent) died.
    • Median OS was 8.5 years.
    • The correlation between TTM and OS was 0.25 (P < 0.0001),
  • Among 247 men assessed from onset of castration resistance (Group Y)
    • 172/247 (70 percent) developed metastasis.
    • Median TTM was 2.6 years.
    • 140/247 (56 percent) died.
    • Median OS was 5.25 years.
    • The correlation between TTM and OS was 0.32 (P < 0.0001).
  • Within Group X a subset of patients developed metastasis within 5 years.
    • Among this subset of patients, the hazard ratio (HR) for mortality was 7.42 (p < 0.0001).
  • Within Group Y a subset of patients became castration resistant within 3 years.
    • Among this subset of patients, the hazard ratio (HR) for mortality was 5.25 (p < 0.0001).

Valenca et al. conclude that their data show a close correlation between TTM and OS in patients with biochemically recurrent disease treated by ADT (but they also note that prospective studies will be needed to decide whether TTM can be used as a surrogate endpoint for OS in clinical trials).

Now it can not be concluded definitively from these data that there is also a correlation between the aggressiveness of prostate cancer at diagnosis (based, for example, on things like PSA level, Gleason score, and genetic make-up of the tumor) and overall survival (OS), but it would hardly be a surprise to find that this was the case. It is also unsurprising to note that the median survival of many men who receive modern, approved (and investigational) forms of therapy for progressive prostate cancer can have survival times of > 10 years from onset of disease progression.

4 Responses

  1. These are “hard facts” and, though not very encouraging for those so diagnosed, necessary so that they ensure they are provided necessary aggressive treatment and recognize the importance of appropriate diet, nutrition, and stopping any practices that may contribute to cancer cell growth — thus likely a drastic change in their lifestyle to slow down advancement to TTM and OS as much as possible.

    A few other papers in this regard can be found here, here, and here.

  2. Not encouraging for men with metastasis at diagnosis, but …

    As Chuck Maack noted, the results in the first study for men with metastatic disease at diagnosis — Group A — look a lot like what we have seen from earlier years, before the recent group of impressive new drugs (and revitalized docetaxel) were approved and used in this study; as of the end of last year, the 5-year survival rate for men with distant metastases at diagnosis was still only 28% per the American Cancer Society, a figure that has not budged for years. That’s discouraging! (And in sharp contrast to soaring success of 94% survival at 15 years for all prostate cancer patients per the ACS at the end of last year, even including those with metastases at diagnosis.)

    On the other hand, some drugs, such as Xofigo that delivers potent, targeted spot radiation to bone metastases was very likely not available to these patients. Moreover, the study does not mention whether these patients used the supportive infrastructure of lifestyle tactics and drugs (such as statins, metformin) that many of us use. Also, imaging has continued to improve since these men were being treated, as has knowledge about how the new drugs can be used in a complementary fashion. Additionally, emerging drugs such as ipilimumab seem to have potential to have a substantial impact for this group of patients.

    Finally, the relatively poor outcomes for men with metastases at diagnosis deeply underscores the importance of smart screening to catch prostate cancer at earlier stages, and that is a further searing indictment of the US Preventive Services Task Force, which blundered in considering the science (and continues their blunder as of today despite much more evidence against their position). I would dearly like to know if some of the patients in this study, which covered patients between 2008 and 2013, had elected not to have a PSA test because of the Task Force’s negative recommendation in 2010.

  3. Dear Jim:

    Much as you may wish to be able to blame the USPSTF for increasing risk of diagnosis with de novo metastases, I think I have to point out to you that the study by Akamatsu et al. is based on patients diagnosed and managed in Canada and not in the USA, so any impact of the USPSTF’s recommendation would have been minimal … especially since about half the patients would probably have been diagnosed prior to issuance of that recommendation in any case.

  4. Point taken. Obviously, I get pretty steamed when thinking about the Task Force. Several of us from our Virginia Prostate Cancer Coalition man booths at health expos, and we frequently hear questions from men and women who know about the Task Force’s negative recommendation and accepted that as the wise course to follow. We do our best to inform them. I try my best to be dispassionate and rely just on the facts and logic, which are compelling enough on their own.

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