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.
Authors: Abhishek Tripathi, Yu-Hui Chen, David Frazier Jarrard, Jorge A. Garcia, Robert Dreicer, Glenn Liu, Maha H. A. Hussain, Daniel Shevrin, Matthew M. Cooney, Mario A. Eisenberger, Manish Kohli, Elizabeth R. Plimack, Nicholas J. Vogelzang, Joel Picus, Michael A Carducci, Robert S. DiPaola, Christopher Sweeney
Journal: Journal of Clinical Oncology (2025)

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 (&lt;0.2 vs. ≥0.2) groups using the log rank test. Results: A total of 334 patients achieved PSA nadir of &lt;0.2 at any timepoint with a median time to PSA nadir of 4.8 months. At 6 months, PSA nadir &lt;0.2 was seen in 204 (26.8%) patients. Patients with PSA nadir &lt;0.2 had significantly better median OS in both ADT + D (100.3 vs. 45.4 mos; P&lt;0.0001; Table) and ADT (116.8 vs. 31.8 mos; P&lt;0.0001) arms. This prognostic impact was significant across prespecified prognostic subgroups. Of the 101 patients who achieved a PSA of &lt; 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 &lt;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 &lt;0.2 66/127 100.3 (70.4, NA) &lt;0.0001 35/77 116.8 (87.3, 141.5) &lt;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 &lt;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 &lt;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 &lt;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)