Impact of exposure to clinical trials and standard-of-care therapy in metastatic or recurrent prostate cancer: An update.

Abstract

76 Background: Treatment (tx) options for metastatic prostate cancer (mPC) have advanced significantly. Literature shows that access to, and uptake of, clinical trials or standard intensified tx in mPC may be low. Methods: We conducted further survival analysis on all consecutive patients (pts) diagnosed with any stage of PC between 2016-2017 in British Columbia, and only included pts with de novo metastasis or later recurrence. We performed descriptive statistics, univariate and multivariate analysis to examine overall survival (OS). Results: This study included 796 pts with either de novo metastatic (n=554, 69.6%) or recurrent PC (N=242; 30.4%); 743 (93.3%) had metastasis by time of cutoff (Sep 1, 2022). Median age at diagnosis of mPC in all patients was 73 (range 45-98). 790 (99.2%) started androgen deprivation tx (ADT). 263 (35.4%) had additional line of tx started with ADT at hormone sensitive mPC (mHSPC); 309 (38.8%) had 1st line tx started at castrate resistant mPC (mCRPC). Radiotherapy (RT) to prostate for mPC were given to 93 (11.6%). 307 (38.6%) received 1 line of tx; 181 (22.7%), 2; 128 (16.1%), 3 or more. 432 (54.3%) received ≥1 androgen receptor pathway inhibitors (ARPI). At cutoff, 474 (59.5%) died; most (n=400; 84.4%) died of prostate cancer. 35 pts who went on trial had longer mOS than those who did not go on trial (63.6 vs 39.5m, p=0.025). Pts with 5 or 6 lines of therapy had numerically longer but statistically similar mOS than those who had 1 (51.7m vs. 63.7m vs. 38.1m, p=0.47). Pts who got 1 line of ARPI had statistically similar mOS than those not exposed to ARPI (43.3m vs. 39.5m, p=0.89). In pts with de novo mPC, more than 1 line (44.3m) or 1 line of ARPI (42.1m) were associated with numerically longer but statistically similar mOS compared to no ARPI (30.1m, p=0.47); pts with recurrent mPC showed an opposite trend (22.5 vs 48.5m vs. not reached, p=0.009). In multivariable analysis, RT to prostate for mPC was associated with better mOS in mHSPC (HR 0.409, 95% CI 0.180 – 0.92, p=0.032) but not mCRPC. None of age, PSA at metastasis, Gleason score, or ADT type was identified as an independent factor affecting mOS. No significant differences in mOS was seen with varying years of mPC diagnosis (2015-2022). Conclusions: Our multicentre data suggest that access to clinical trials and timely RT to prostate in appropriate pts with mPC are associated with longer mOS and should be considered standard of care. Access to clinical trials may be challenging for a significant proportion of pts. Exposure to as many lines of tx/ARPI as possible may potentially help in pts with de novo mPC, but more data are required to determine benefit in all subgroups.