Debulking the primary tumor in men diagnosed with metastatic prostate cancer


There has long been an unanswered question about the value of “debulking” of the primary tumor in men who are initially diagnosed with advanced forms of prostate cancer — i.e., surgical removal of the prostate or some form of definitive radiation therapy of the primary tumor.

Surgical specialists at the Mayo Clinic have long advocated in favor of this type of treatment (combined with adjuvant androgen deprivation therapy) for men with node-positive prostate cancer, and they have also published limited data on debulking of the primary tumor in men with evident metastatic disease.

Now a paper by Culp et al. in European Urology has provided some preliminary data to suggest that debulking of the primary tumor may have a long-term, survival benefit in at least some men with evident metastatic disease at time of diagnosis. (It should be noted that debulking of the primary tumor is relatively commonplace in several other types of solid tumor even when metastasis is evident.)

Culp et al. set out to look very specifically at whether the survival of men diagnosed with metastatic prostate cancer might be affected by definitive
treatment of the prostate itself. To do this, they used Surveillance Epidemiology and End Results (SEER) data for the period 2004 to 2010 for patients initially diagnosed with TxNxM1a–c disease (equivalent to Stage IV disease based on the American Joint Committee on Cancer or AJCC staging system) and divided the men into three groups:

  • Men who received a radical prostatectomy with or without adjuvant external beam radiation therapy (the RP group)
  • Men who received brachytherapy with or without adjuvant external beam radiation therapy (the BT group)
  • Men who received no form of surgery or radiation therapy at all (the NSR group)

Here are the basic findings of their study:

  • 8,185 patients could be identified.
    • 245 men were in the RP group.
    • 129 men were in the BT group.
    • 7,811 men were in the NSR group.
  • Average (median) follow-up was 16 months.
  • 3,115/8,185 patients (38.1 percent) died of prostate cancer.
    • 33/245 men (13.5 percent) were in the RP group.
    • 34/129 men (26.4 percent) were in the BT group.
    • 3,048/7,811 men (40.7 percent) were in the NSR group.
  • The projected 5-year overall survival was
    • 67.4 percent among men in the RP group
    • 52.6 percent among men in the BT group
    • 22.5 percent among men in the NSR group
  • The projected 5-year prostate cancer-specific survival was
    • 75.8 percent among men in the RP group
    • 61.3 percent among men in the BT group
    • 48.7 percent among men in the NSR group
  • Having a radical prostatectomy or having brachytherapy were each, independently, associated with a lower risk for prostate cancer-specific mortality.
  • Results were similar regardless of the substage of metastatic disease.
  • Risk for prostate cancer-specific mortality among the men in the RP and the BT groups included
    • The presence of stage T4 disease
    • The presence of high-grade disease
    • A PSA level at diagnosis > 20 ng/ml
    • Age of 70 years of more
    • The presence of node-positive disease
  • Among 1,284 men who died of causes other than prostate cancer (15.7 percent of the patients identified), there were no significant differences in survival among the three groups.

The authors are careful to point out that there are a number of limitations to the interpretation of the data available from this analysis, the most important of these being the lack of information in the SEER database about variables known to influence the survival of patients with metastatic prostate cancer (including treatment with systemic therapies). However, the authors still feel able to conclude that

Definitive treatment of the prostate in men diagnosed with [metastatic prostate cancer] suggests a survival benefit in this large population-based study. These results should serve as a foundation for future prospective trials.

The “New” Prostate Cancer InfoLink has long suspected that debulking of the primary tumor might extend survival in at least a subset of men initially diagnosed with metastatic prostate cancer (i.e., those men with less aggressive forms of metastasis). The data provided by Culp et al. appear to support this concept. However, it has to be emphasized that these are very limited data and that considerable thought would need to go into how one might construct any type of clinical trial to investigate the the value of debulking of the primary tumor in patients with an initial diagnosis of metastatic disease.

The entire paper by Culp et al. is available on line, and we would recommend downloading and reading this paper to all support group leaders, advocates, and others who have responsibilities related to the education of physicians and patients regarding the management of prostate cancer in general and advanced forms of prostate cancer in particular.

3 Responses

  1. For those who participate in Twitter there has been a spirited discussion at #urojc between top urologists, including one of the authors of this paper. Enlightening to discover the view of uro teachers, professors and practitioners to this type treatment.

  2. I am sorry to be critical yet again, but sadly I think this study makes it hard to justify much enthusiasm for local treatment in men with metastatic disease. Everyone acknowledges that retrospective analyses do not do much more than offer an idea for a prospective study and the authors do not draw excessive conclusions. However, here are some of the reasons the data may be very misleading:

    — PSA less than 10 occurred in 8% of the non-local treatment group vs 47% and 35% for the other two groups.
    — Tumor stage was unknown in 25% of the non-local treatment group vs less than < 1% and 14% in the other two groups.
    — N0 (i.e., N zero) disease was present in 49% of the non-local treatment group vs 67% and 70% of other two groups.

    No discussion is provided of either the use of hormone therapy or chemotherapy nor the impact on quality of life or complications of treatment.

    The bottom line is there are many reasons why the results of this study may be biased in favor of local therapy. Is a prospective study worth doing? On the basis of this study, I don't think so.

  3. Dear Dr. Chodak:

    I don’t see that you need to apologize for expressing your carefully considered and well-expressed opinion.

    :O)

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 )

Google photo

You are commenting using your Google 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: