Patient Reported Outcomes in High-Risk Prostate Cancer Patients with or without Testosterone Recovery after Androgen Deprivation Therapy

Abstract

In a previous report from a randomized trial of 630 patients (pts), we showed that 18 months of androgen deprivation therapy (18m ADT) appears to be equally effective as 36 months (36m ADT) in high-risk prostate cancer (HRPC) pts. We performed the current analysis to evaluate quality of life (QOL) using the 25 items of EORTC PR25 validated tool in pts with or without testosterone (T) recovery after ADT. We selectedpts with no biochemical failure to avoid subsequent T variations due to reintroduction of ADT for recurrence. Patients receiving exactly 18 or 36m of ADT, survived more than one year (y) post randomization, had T measured at baseline and during follow-up and who completed QOL questionnaire entered this review. The 25 items were regrouped into 5 scales. All items and scales scores were linearly transformed to a 0-100 points scale. Serum T was measured at baseline then at each visit. We defined unrecovered testosterone as measured below the normal level. All items and scales scores were analyzed with general linear model and repeated measures to evaluate changes between pts with or without T recovery over time. T recovery was adjusted in a multivariable model including age, initial normal/unrecovered T and ADT (18 or 36m). P-value < 0.01 was considered statistically significant and a difference in mean scores of ≥10 points was considered clinically relevant. Patient-reported outcomes were filled out before treatments, every 6m during ADT, 4m after ADT and then once a year for 5y. Two hundred sixty nine of 630 pts met the eligibility criteria and were retained for the analysis. At a median follow-up of 14 years, 140/269 (52.0%) pts recovered T to normal level: 94/166 (56.6%) in 18m ADT and 46/103 (44.7%) in 36m ADT, p = 0.056. The median time to recovered T was significantly lower in 18m vs. 36m ADT (3.04 vs. 5.06 y, p<0.001). The global adherence to QOL questionnaires was 83.9% (2649/3156) and was similar between arms. Pts recovering T compared to those who did not, had a better QOL. 6/20 items [difficult to get enough sleep: get up frequently at night to urinate, blood in stool, hot flushes, feel less man, interested in sex, sexually active (with or without intercourse)] and 2/4 scales (treatment and sexual activity) were statistically significant (all p<0.01). 2 items were also clinically relevant: hot flushes and interested in sex. Hot flushes were clinically relevant (more than 10 point of difference) between 3.5 to 5y inclusively with maximum difference of 19.4 point. Interest in sex was clinically relevant with 13.1 point of difference at 3 years. T recoverypost long-term ADT is associated with a significantly improved QOL in patients with HRPC. Considering similar prostate cancer clinical outcomes and faster T recovery, our results suggest that 18m ADT may be the most appropriate ADT treatment duration for these patients.