Post-surgical salvage radiation therapy and all-cause patient mortality


An article just published on-line in Cancer has demonstrated that, in a cohort of men with a median follow-up of  > 10 years, salvage radiation therapy (after first-line radical prostatectomy) reduces all-cause mortality in men with short (< 6 months) and longer (≥ 6 months) PSA doubling times at the time of initial biochemical disease progression.

In 2008 Trock et al. reported that (in a cohort of patients followed for a median of 6.3 years) there was a prostate cancer-specific survival benefit associated with salvage radiation therapy (RT) in men who had biochemical failure after radical prostatectomy (RP) and who had rapid rises in their PSA doubling time (PSADT), i.e., PSADT values of < 6 months. What has not previously been clear is whether a comparable benefit was evident in men with a PSADT of ≥ 6 months.

This new report by Cotter et al. is based on a retrospective analysis of data from 4,036 men initially treated by RP at Duke University between 1988 and 2008. Of these 4,000+ patients, 519 experienced biochemical failure and sufficient data were available to allow them to be included in the present analysis.

Post-surgical treatment of these 519 patients could be categorized into groups, as follows:

  • The men who received salvage RT (n = 219), including
    • 134 men who received salvage RT alone
    • 39 men who received salvage RT and concurrent androgen deprivation therapy (ADT)
    • 52 men who received salvage RT and later ADT
    • 4 men who received ADT and later salvage RT
  • The men who did not receive salvage RT (n = 300), including
    • 199 who received no further therapy
    • 101 who received only ADT

The core results of this study are as follows:

  • 158/519 men (30.4 percent) had a PSADT of < 6 months.
  • 361/519 men ( 69.6 percent) had a PSADT of ≥ 6 months.
  • Compared to the men with a PSADT of ≥ 6 months, men with a PSADT of < 6 months were
    • Younger at the time of PSA failure (median age, 65.6 vs. 68.1 years)
    • More likely to have pathologic Gleason scores of 7 and higher (86 vs. 72 percent)
    • More likely to have pT3 or pT4 disease (76 vs. 66 percent)
    • More likely to receive salvage treatment (73 vs. 57 percent)
  • After a median follow-up of 11.3 years from the time of PSA failure, 195/519 men (37.6 percent) had died (of all causes).
  • The application of salvage RT was associated with a significant reduction in all-cause mortality for men with a PSADT of < 6 months (adjusted hazard ratio [AHR] = 0.53; P = 0.02).
    • 46/88 men (52.3 percent) with a PSADT of < 6 months who received salvage RT had died.
    • 34/70 men (48.6 percent) with a PSADT of < 6 months who did not receive salvage RT had died.
  • The application of salvage RT was associated with a significant reduction in all-cause mortality for men with a PSADT of ≥ 6 months (AHR = 0.52; P = 0.003).
    • 65/212 men (30.7 percent) with a PSADT of ≥ 6 months who received salvage RT had died.
    • 50/149 men (33.6 percent) with a PSADT of ≥ 6 months who did not receive salvage RT had died.
  • In a subset of patients with available comorbidity data at the time of PSA failure
    • Salvage RT was still associated with a significant reduction in all-cause mortality for men with a PSADT of < 6 months (AHR = 0.35; P = 0.042).
    • Salvage RT was still associated with a significant reduction in all-cause mortality for men with a PSADT of ≥ 6 months (AHR = 0.60; P = 0.04).

Perhaps the first and one of the most important points to note in this study is that even among the patients with a PSADT of < 6 months at the time of PSA failure, only 80/158 men (50.6 percent) had died of any cause after a median follow-up of 11.3 years. Among the men with a PSADT of ≥ 6 months, only 115/361 (31.9 percent) had died within this median follow-up period.

It is clear from these data that salvage RT is associated with a statistically significant decrease in all-cause mortality in men with post-surgical biochemical progression and with PSADT values of < 6 and ≥ 6 months after adjustment for differences in age at time of PSA failure, “known prostate cancer prognostic factors,” and comorbidities (as assessed by the use of the adjusted hazard ratio).

What these data do not tell us, however, is whether salvage RT provides such a benefit for men with truly extended PSADT values (of 12 months or longer). A PSADT of 6 to 9 months is still a relatively rapid PSADT, but once PSADT values start to get to a year and more, we already know that such values are associated with a significant reduction in risk for metastatic disease and prostate cancer-specific mortality. It is therefore fair to enquire whether salvage RT has a survival benefit in these groups of patients.

We hope that the current research team will, in time, be able to apply the Duke data (or other data) to investigate this question too. The current median follow-up time of 11.3 years is probably still not long enough to offer an accurate assessment of the impact of long PSADT values at the time of biochemical progression on prostate cancer-specific or all-cause mortality.

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