PSA Failure Associated With Mortality in Prostate Cancer Patients With Little Comorbidity

Prostate-specific antigen (PSA) failure in men with localized, intermediate-, or high-risk prostate cancer was associated with increased all-cause mortality in only those patients with no or minimal comorbidity, and not those with more comorbidity, according to a new study. Guiding treatment decisions based on PSA failure could be considered in certain men based on these results.

Recent research has shown that adding androgen deprivation therapy (ADT) to radiation therapy can improve survival, but only in men with little or no comorbidity. “This raises the question as to whether time to PSA failure, an endpoint that often occurs many years before metastasis and death from prostate cancer, is a clinically relevant endpoint only in men who have no or minimal comorbidity,” wrote study authors led by Nicholas J. Giacalone, MD, of Brigham and Women’s Hospital in Boston.

Some other recent trials found that relapse-free survival improvements have been driven by PSA failure-free survival, but without actual overall survival or prostate cancer-related mortality benefits. Taken together, these raise the question of whether comorbidity should be considered when determining treatment based on such trial results. In the new study, researchers analyzed data from a trial with 206 men with localized, intermediate-, and high-risk prostate cancer who were randomized to either radiation therapy alone or radiation therapy plus 6 months of ADT, to see if PSA failure was associated with all-cause mortality. The results were published online ahead of print in the Journal of Clinical Oncology.

After a median follow-up of 16.62 years, 156 men in the trial died (76%); of those, 29 men (19%) died as a result of prostate cancer. Of the 49 men with moderate or severe comorbidity, 49 died (94%); of those with no or minimal comorbidity, 110 of 157 died (70%).

PSA failure was seen in 54.14% of men with little or no comorbidity and in 46.94% of those with moderate or severe comorbidity; this difference was not significant (P = .38).

Among the men with little or no comorbidity, PSA failure significantly raised the risk of all-cause mortality, with a hazard ratio (HR) of 1.59 (95% CI, 1.03–2.46; P = .04). For the men with moderate or severe comorbidity, however, though the HR was larger it was not statistically significant, at 1.75 (95% CI, 0.76–3.99; P = .19). In the former group with less comorbidity, the age-adjusted 15-year all-cause mortality rate was 69.1% when PSA failure was observed and 56.6% when it was not; in the more comorbid group, these rates were 87.7% and 81.4%, respectively.

“Recommending treatment on the basis of the reduced PSA failure observed in early results of randomized controlled trials 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,” the authors concluded.