Quality of life and testosterone recovery after androgen deprivation therapy in patients with high-risk prostate cancer: Long-term data from a phase III trial.

Abstract

11098 Background: No prospectively collected data exist assessing the impact a hypogonadal status has on quality of life (QoL). Using data from a randomized Phase III trial in high-risk prostate cancer (HRPC) and based on Patient Reported Outcomes (PRO), we compared QoL between patients (pts) with or without testosterone (T) recovery after ADT. Methods: From 10/2000 to 01/2008, 630 pts with HRPC were randomised to 36 (310 pts) vs. 18 months (320 pts) of ADT. We assessed QoL by the validated EORTC 30 items regrouped into 9 scales and the PR 25 items into 5 scales. All items and scales scores were linearly transformed to a 0 to100 points scale. T measured at baseline and during follow-ups. T recovery was defined as a return to normal level. PRO measured up to 5 years. We estimated means and standard deviation of items and scales for each group at each time point. We analyzed all items and scales scores with general linear model with repeated measures to evaluate changes between patients who did versus those who did not recover T to a normal level, over time, in both ADT groups. P-value <0.01 was considered statistically significant to account for multiple comparisons and a difference in mean scores of ≥10 points was considered clinically relevant. Results: 494/630 patients were retained for the analysis. 515 had proper T data available (baseline and follow-up) from whom 21 were excluded (no QoL data). With a median follow-up of 13.1 years, the two groups were well-balanced. Over a period of 21 years, 5 982 T measurements were available: 3590 in 314 pts in the and 2392 in the 18- and 36-month cohort, respectively. A total of 256 (51.8%) recovered T to, at least, a pre-castrate level. A significantly higher percentage of pts recovered a normal T level in the 18-month cohort as compared to the 36-month (56.4% vs. 43.9%, p=0.008). Among pts regaining T to a normal level, the median time to recovery was significantly faster for the 18 compared to the 36-month cohort, 3.0 (95% CI: 2.55 to 3.65) vs. 5.00 (4.50 to 5.96) years, p<0.001. Considering the unified 55 items, overall adherence to QoL questionnaires (QoLQ) was 83.1% (4554/5480), 88.2% vs. 93.3% at baseline and 61.5% vs 58.3% at 5 years, for 18 vs. 36-month, respectively. Patients recovering T had a significantly better QoL. In 32 out of 55 items and in 10 out of 21 scales (p<0.01) in the 18-month and 30 out of 55 items and 10 out of 21 scales the 36-month cohort. Also 9 items and one scale reached clinical relevance in the 18-month cohort and 10 items and one scale in the 36-month cohort. Conclusions: In HRPC treated with RT and long-term ADT, T recovery to normal level is associated with major improvements in QoL in several domains. Since a higher proportion of pts recover a normal T level in a much shorter time without apparent detriment in long term outcomes, our results suggest that 18-month may be the most appropriate ADT duration for these pts.