The landmark CHAARTED trial transformed the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) by demonstrating that adding docetaxel to androgen deprivation therapy (ADT) significantly improves overall survival.
A recent post hoc analysis, updated with survival data through July 2024, has gone further by examining 10-year outcomes, causes of death, and the prognostic value of prostate-specific antigen (PSA) nadir at six months.

The analysis included patients randomized to ADT alone or ADT plus docetaxel (ADT+D). They were prospectively stratified by disease state, metachronous (after local therapy) or synchronous (no prior local therapy), and by disease burden, with high-volume disease defined as visceral metastases and/or at least four bone metastases, one of which extended beyond the vertebral bodies or pelvis. Survival was measured from six months post-randomization, and outcomes were compared between those achieving a PSA nadir below 0.2 ng/mL at six months and those who did not.

A clear finding emerged: patients who reached a PSA <0.2 ng/mL at six months experienced dramatically better outcomes. Of the 334 men who ever achieved this threshold, the median time to nadir was 4.8 months, underscoring the prognostic importance of early response. At six months, 204 patients (26.8%) had already reached the benchmark. Across both treatment arms, median overall survival more than doubled for these men compared with those whose PSA remained ≥0.2 ng/mL. In the ADT+docetaxel group, survival was 100.3 months versus 45.4 months (P<0.0001), while in the ADT alone group, survival was 116.8 months versus 31.8 months (P<0.0001). Approximately half of the patients who achieved a low PSA nadir at six months were still alive eight years later, demonstrating the durability of this prognostic signal.

This advantage was consistent across prespecified subgroups:

Overall population:

• ADT+D: 100.3 vs. 45.4 months
• ADT alone: 116.8 vs. 31.8 months

De novo high-volume disease:

• ADT+D: 93.5 vs. 39.5 months
• ADT alone: 74.7 vs. 26.4 months

Metachronous high-volume disease:

• ADT+D: 105.7 vs. 43.2 months
• ADT alone: 87.3 vs. 22.1 months

Metachronous low-volume disease:

• ADT+D: 101.5 vs. 63.6 months
• ADT alone: 123.4 vs. 48.9 months

Beyond overall survival, the analysis of cause of death further highlighted the impact of an early PSA nadir. Among patients with PSA <0.2 ng/mL at six months, 58.4% of deaths were attributed to prostate cancer, compared with 78.2% in the ≥0.2 group. Deaths from non-cancer causes were proportionally higher among those with a deep early PSA response, while prostate cancer progression accounted for most deaths in men who failed to reach the threshold.

In summary, this long-term analysis of the CHAARTED trial confirms that achieving a PSA nadir below 0.2 ng/mL at six months is a powerful predictor of survival in metastatic hormone-sensitive prostate cancer. Patients reaching this threshold had more than double the median overall survival and fewer prostate cancer–related deaths, with benefits seen consistently across treatment arms and clinical subgroups. These findings establish early and profound PSA response as one of the most critical indicators of long-term outcome in this disease.

Source.