Delaying surgery for localized prostate cancer … what’s the downside?

A paper published in June this year in the Journal of Sexual Medicine suggests that delaying radical prostatectomy (RP) as a first-line treatment for localized prostate cancer has no significant effects on post-surgical pathology or mortality but may lead to higher risk for incontinence and erectile dysfunction. Whether this is a valid conclusion is likely to be controversial based on the data used to reach this conclusion.

The study by Sun et al. was intended to assess whether the time from diagnosis to actual surgery for men with low-grade, localized prostate cancer (clinical stage T1 or T2) had definable effects on postoperative functional outcomes and mortality in a U.S. population-based cohort derived from data in the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database.

The authors extracted data from the SEER-Medicare database for more than 17,000 men treated by radical prostatectomy for low-grade, early stage, non-metastatic prostate cancer between 1995 and 2005. They then used statistical and other methods to look at the effect of a delay of more than 3 months from diagnosis to RP on pathological upstaging at surgery (≥ pT3) and postoperative functional outcomes (urinary incontinence and erectile dysfunction). They also calculated the 10-year prostate cancer mortality rates for the patient sets using cumulative incidence rates.

Here are the results stated in the abstract of the paper:

  • The total number of patients identified in the SEER-Medicare database who met the eligibility criteria was 17,153.
  • 2,576/17,153 patients (15 percent) were given an RP more than 3 months after their initial diagnosis.
  • Compared to men treated within 3 months of diagnosis, men treated > 3 months after diagnosis had
    • No evidence of increase in risk for pathological upstaging
    • No evidence of increase in risk for prostate cancer-specific mortality
    • A 24 percent higher rate of diagnosis of erectile dysfunction
    • A 33 percent higher rate of some form of procedure for erectile dysfunction
    • A 6 percent higher rate of some form of procedure for urinary incontinence
  • Longer treatment delay (i.e., ≤ 3 vs. 3-5 vs. 5-9 vs. ≥ 9 months) was associated with a higher risk for diagnoses and/or procedures to manage erectile dysfunction and urinary incontinence.

During the period from 1995 to 2005, active surveillance was a relatively uncommon method used for the management of low-risk, localized prostate cancer. It is therefore reasonable to assume (as the authors appear to do ) that

  • Many patients diagnosed with localized prostate cancer needed time to understand their options before making an informed decision regarding treatment.
  • Men with intermediate- and high-risk forms of localized prostate cancer would have been more likely to have received treatment as soon as possible after their diagnosis (i.e., within 3 months) because of the presumed aggressiveness of their cancer

However, we can not necessarily take the next step that is proposed by the authors, who state that, “The treatment delay between biopsy and RP may result in more extensive periprostatic tissue resection and may adversely affect postoperative continence and erectile function” among men who (through choice or as a consequence of scheduling) have an RP > 3 months after their initial diagnosis.

It is certainly the case that deferring treatment may have specific consequences for some men. However, the data on which the authors draw their current conclusions are highly unlikely to contain enough clinical information to know either exactly why treatment was deferred or what consequences may have been incurred as a result of the delay. It should also be noted that men defined as having “low-risk” disease in 1995-2000 probably had somewhat more advanced cancer than those being diagnosed in 2000-2005 (let alone those being so-diagnosed today).

We should point out that we have only seen the abstract of this paper, and the full text is likely to contain all sorts of disclaimers regarding the accuracy of the results and the conclusions. The hypothesis proposed by the authors does raise questions that need to be addressed, however. We suspect there are sufficient data from various clinical registry databases to be able to directly compare the rates of incontinence and sexual dysfunction among men treated with radical prostatectomy and correlate these rates not only to time from diagnosis to surgery but also to detailed information on staging, Gleason scores, the use of active surveillance, etc.

It certainly would be disturbing if we were to see a clear association between time from diagnosis to treatment and risk for side effects of treatment in prospectively collected data from one or more large, carefully monitored cohorts of patients because it would undermine the entire premise behind the value of active surveillance — at least for younger men who were being led to believe that “treatment later” would be as effective and safe as “treatment now.”

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