PSA at 7 Months Prognostic in Treated mHSPC

Patients with metastatic hormone-sensitive prostate cancer (mHSPC) who achieve a PSA level of 0.2 ng/mL or less at 7 months after initiation of androgen deprivation therapy (ADT), with or without docetaxel, have longer overall survival, according to a new study.

The 719 patients in the current analysis had participated in the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) study, a phase III, open-label trial in which investigators randomly assigned patients to receive either ADT alone or ADT plus 6 cycles of docetaxel. The cohort included 358 patient treated with ADT plus docetaxel and 361 treated with ADT alone.

The cohort had a median follow-up of 23.1 months starting 7 months after ADT initiation. Overall survival across all patients was significantly longer if the 7-month PSA level was 0.2 ng/mL or less compared with a level greater than 4 ng/mL (median 60.4 vs 22.2 months) according to Lauren C. Harshman, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues who reported online ahead of print in the Journal of Clinical Oncology. On multivariable analysis, a 7-month PSA level of 0.2 ng/mL or less was associated with an 82% decreased risk of death compared with a 7-month PSA level above 4 ng/mL.

“PSA is attractive as a much earlier biomarker of improved clinical outcomes than overall survival, but requires further prospective study to prove it a true surrogate,” Dr. Harshman told Renal & Urology News. “Our results also highlight outstanding questions regarding intensification of therapy and whether patients who don’t experience this ideal PSA should intensify the current therapy.”

For example, she noted, if a patient is on ADT alone, should docetaxel be added to try to induce a PSA level of 0.2 ng/mL?

Patients who received ADT alone and achieved a 7-month PSA of 0.2 ng/mL or less had the best survival (median 72.8 months). Median survival was the worst at 21.6 months among ADT-only recipients whose 7-month PSA was above 4 ng/mL. Patients receiving ADT and docetaxel who achieved a 7-month PSA level of 0.2 ng/mL or less had a significantly greater median survival of 60.4 months compared to those whose 7-month PSA level remained above 4 at 25.2 months.

On multivariable analysis, after 7 months of ADT, the risk of death was 50% lower among those with low-volume versus high-volume disease. Compared with ADT alone, ADT plus docetaxel was associated with approximately 2.6-fold increased odds of achieving a PSA of 0.2 ng/mL or less at 7 months.

In their acknowledgement of study limitations, the authors noted, “It is likely that the CHAARTED study as a whole was subject to selection bias in terms of which patients were referred for a study that included chemotherapy.”

In addition, their analysis was limited to patients with at least 7 months of follow-up after ADT initiation and patients who had a 7-month PSA value available. Of the 790 patients originally enrolled in the CHAARTED study, 71 were excluded, 36 because they had less than 7 months of follow-up after ADT initiation and 35 because they lacked a 7-month PSA assessment. “These criteria may have biased the results somewhat toward patients with a better risk profile because they survived at least 7 months after ADT and/or were not lost to follow-up in that same time frame.” However, the authors thought this an unlikely major contributor to bias as only 36 patients were excluded out of 790, and those with rapidly progressive disease before 7 months do not need an intermediate clinical endpoint such as 7-month PSA for prognostication.