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