Introduction

We aimed to assess the risk of cancer-specific mortality (CSM) in patients with PSA persistence after radical prostatectomy (RP) after accounting for other-cause mortality (OCM). We hypothesized that a non-negligible proportion of patients is at risk of dying from other causes and would not benefit from additional cancer therapies.

Methods

We included 829 patients with localized PCa undergoing RP at two referral centers between 1994 and 2014. All patients had PSA persistence after RP defined as a PSA ≥0.1 ng/ml at 8 weeks after surgery. A graphical illustration of the 10-year CSM and OCM rates was generated using competing-risks Poisson regression analyses. Patients were stratified according to age (<65 vs. ≥65 years) and according to their probability of dying from PCa at 10-years (stratified as <10% vs. 10-30% vs. >30%), which was developed from a Cox regression model based on pathologic characteristics and first PSA after surgery. For each strata, survival estimates were calculated. Competing-risks regression models were used to test the effect of age and disease characteristics on CSM after accounting for OCM

Results

Overall, 223 (26.9%), 331 (39.9%), and 275 (33.2%) patients had pathologic Gleason score ≤6, 7, and ≥8, and 400 (48.3%), 215 (25.9%), 214 (25.8%), and 172 (20.7%) patients had pT2, pT3a, pT3b/4, and pN1 disease. The median first PSA after surgery was 0.33 ng/ml. Median follow-up was 107 months, during which time 90 and 136 patients died from PCa and from OCM. The 10-year CSM and OCM rates were 12.6% and 11.9%. When considering men with a risk of dying from PCa <10%, the 10-year rate of OCM was higher as compared to the CSM rate (8 vs. 1.6%), regardless of age. The proportion of patients who died from OCM at 10-year was 4.2% in men <65 years with a probability of dying from PCa >30% vs. 18.2% in patients ≥65 years with a probability of CSM between 10 and 30%. In men with a calculated risk of dying from PCa >30% the 10-year CSM rates were 43.7 vs. 34.1% for those aged <65 vs. ≥65 years old. At multivariable regression analyses, the number of positive nodes, first PSA after surgery, and pathologic Gleason score 8-10 (all p<0.001) were associated with the risk of CSM after accounting for the risk of dying from other causes.

Conclusions

Up to 20% of men with PSA persistence after RP will ultimately die from other causes. Conversely, patients with Gleason score 8-10, higher PSA after surgery, and a higher number of positive nodes are at increased risk of CSM. These patients might benefit from additional cancer therapies, while men less likely to die from PCa may be spared such treatments.

Funding

none