Impact of PSA nadir on long-term survival in metastatic hormone-sensitive prostate cancer: Final 10-year analysis of the ECOG-ACRIN E3805 CHAARTED trial.

167 Background: Addition of docetaxel (D) to ADT has demonstrated improved overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC). In this post hoc OS analysis of the CHAARTED trial (NCT00309985), we report 10-year OS and cause of death (COD) by baseline clinical factors, PSA nadir at 6 months in mHSPC patients treated with ADT +/- D. Methods: An updated survival sweep was conducted in July 2024. Patients were prospectively identified by the state of metastatic disease (metachronous/prior local therapy vs. synchronous/no prior local therapy) and low volume (LV) vs. high volume (HV; visceral and/or ≥4 bone metastases with one lesion beyond the vertebral bodies or pelvis) disease. OS defined as time from 6 mos post randomization to death was calculated using the Kaplan-Meier method and compared between PSA nadir (<0.2 vs. ≥0.2) groups using the log rank test. Results: A total of 334 patients achieved PSA nadir of <0.2 at any timepoint with a median time to PSA nadir of 4.8 months. At 6 months, PSA nadir <0.2 was seen in 204 (26.8%) patients. Patients with PSA nadir <0.2 had significantly better median OS in both ADT + D (100.3 vs. 45.4 mos; P<0.0001; Table) and ADT (116.8 vs. 31.8 mos; P<0.0001) arms. This prognostic impact was significant across prespecified prognostic subgroups. Of the 101 patients who achieved a PSA of < 0.2 at 6 mos, the COD was ‘prostate cancer’ in 58.4% (n=59), ‘other’ in 14.9% with 26.7% being unknown. Of the unknown/missing (n=27), 10 patients died without a record of having progression. In the PSA nadir ≥0.2 group, the reported COD was ‘prostate cancer’ in 78.2% with 6.5% being ‘other' and 15.4% being unknown/missing. Conclusions: Compared with patients with PSA ≥0.2, PSA nadir of <0.2 at 6 months was associated with less prostate cancer deaths and more than doubling of the median OS with approximately 50% of patients alive at 8 years across treatment and all prespecified prognostic groups except de novo high volume treated with ADT alone. Clinical trial information: NCT00309985 . Outcomes by PSA nadir at 6 months in overall population and pre-specified subgroups. ADT+ D ADT # Death/N Median OS (95% CI; months) p-value # Death/N Median OS (95% CI; months) p-value Overall 6-month PSA <0.2 66/127 100.3 (70.4, NA) <0.0001 35/77 116.8 (87.3, 141.5) <0.0001 6-month PSA ≥0.2 203/256 45.4 (39.2, 51.6) 246/301 31.8 (26.3, 38.1) Denovo HV6-month PSA <0.2 20/39 93.5 (45.9, NA) 0.0001 7/11 74.7 (37.4, NA) 0.007 6-month PSA ≥0.2 135/166 39.5 (32.8, 48.5) 162/183 26.4 (23.5, 32.0) Metach HV6-month PSA <0.2 12/23 105.7 (61.4, NA) 0.0009 8/15 87.3 (47.4, NA) 0.0002 6-month PSA ≥0.2 22/25 43.2 (23.5, 66.0) 25/26 22.1 (13.9, 39.4) Metach LV6-month PSA <0.2 18/34 101.5 (58.6, NA) 0.04 11/38 123.4 (123.4,141.5) 0.003 6-month PSA ≥0.2 17/21 63.6 (49.7, 99.3) 14/26 48.9 (25.6, NA)