Co-morbidity, outcome, all-cause survival, biochemical recurrence, and additional treatment


So we have all heard the commonly used phrase that men with diagnosed with prostate cancer are “more likely to die with prostate cancer than of it” — and there is certainly truth to this generalization.

As a consequence, it has also long been understood that a prostate cancer patient’s physiological (as opposed to calendar) age and other health issues (co-morbidities) were important in determining the most appropriate way to manage his prostate cancer risk. What we have not known with any certainty, however, is the ways in which biochemical recurrence after first-line treatment for prostate cancer might relate to risk for all-cause mortality among men with differing co-morbidities.

In a new paper in the Journal of Clinical Oncology, Giacalone et al. have now been able to use data from a relatively recent, randomized clinical trial to assess whether PSA failure after first-line radiation therapy (with or without 6 months of androgen deprivation therapy) was associated with risk for all-cause mortality, stratified by the patients’ co-morbidity scores.

The relevant trial enrolled 206 patients with localized (T1b to T2b), intermediate- and high-risk prostate cancer between 1995 and 2001.

What Giacalone et al. were able to show was the following:

  • The average (median) follow-up was 16.62 years.
  • 156/206 patients (75.7 percent) died, of whom 29 died of prostate cancer (14.0 percent of the entire study cohort).
  • PSA failure was associated with increased risk for all-cause mortality among men with no or minimal co-morbidity (adjusted hazard ratio [aHR] = 1.59; P = 0.04).
  • PSA failure was not associated with increased risk for all-cause mortality among men with moderate or severe co-morbidity (aHR = 1.75; P = 0.19).

The authors conclude that:

Recommending treatment on the basis of reduced PSA failure observed from early results of RCTs is unlikely to prolong survival in men with moderate-to-severe comorbidity but may prolong survival in men with no or minimal comorbidity, providing evidence to support discussing the early results with these men.

Another way to look at this is as follows:

Basically, what the authors are saying is that, at least in this group of patients, there was no evidence that early additional treatment of men who had moderate to severe co-morbid conditions and a biochemical recurrence after first-line treatment for prostate cancer (with or without 6 months of ADT) led to an overall, all-cause survival benefit. By contrast additional early treatment may extend overall, all-cause survival in comparable men who had no or just minimal co-morbid conditions, and that discussion of such additional treatment opportunities is therefore entirely appropriate.

Exactly what types of early additional treatment might be appropriate in men no or minimal co-morbidity and biochemical recurrence after first-line radiation therapy would clearly depend on things like the patient’s PSA doubling time and his original diagnosis (PSA level, Gleason score on biopsy, etc.) and the precise location of the disease recurrence (if this can be identified).

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