Shorter PSA Doubling Time Associated with Increased Risk for Death in nmCRPC

Chicago—Of the estimated 40,000 men in the United States with nonmetastatic castration-resistant prostate cancer (nmCRPC), nearly half are at increased risk of developing metastasis or death. Alexander D. Fuld, MD, and colleagues, conducted a retrospective longitudinal study designed to identify the characteristics of patients with nmCRPC and examine the impact of prostate-specific antigen (PSA) doubling time, baseline PSA, and metastases on overall survival. Study results were reported in conjunction with the ASCO 2018 Annual Meeting in a report titled Predictors of Overall Survival (OS) in Veterans with Non-Metastatic Castration Resistant Prostate Cancer (nmCRPC).

The researchers utilized data from the Veterans Health Administration electronic health records from January 2007 through August 2017. Inclusion criteria were castrate testosterone level <50 ng/dL or continuous androgen deprivation therapy when testosterone level was not available, PSA rise ≥25% from nadir with an absolute increase of ≥2 mg/mL (index), and a prostate cancer diagnosis ≤12 months prior to the index date. Exclusion criteria were <12 months of enrollment before and 6 months after index, evidence of metastatic disease 12 months prior to index, or participation in a clinical trial.

Cox proportional hazards model was used to assess overall survival after adjustment for baseline characteristics, log-transformed baseline PSA, PSA doubling time, and a time-varying indicator for metastases (defined as first of diagnosis for metastatic disease, chemotherapy, immunotherapy, radiopharmaceuticals, or oral metastatic CRPC therapy).

Of the 653,747 veterans with a diagnosis of prostate cancer, 49% (n=13,552) were eligible for the nmCRPC study. Mean age was 76.4 years and 66% were white. Mean follow-up was 36 months. During follow-up, there were 6552 deaths (48%); median overall survival was 47 months. Median overall survival was 21 months in patients with a PSA doubling time of <3 months, 36 months with PSA doubling time of 3 to <9 months, and 54 months in patients with PSA doubling time of 9 to <15 months. Doubling time was unknown for 15% of participants.

Results of Cox modeling demonstrated that PSA doubling time was a strong predictor of overall survival. Compared with patients with a PSA doubling time of <3 months, those with a longer PSA doubling time were less likely to die (for PSA doubling time 3 to <9 months, hazard ratio [HR], 0.707, P<.01; for PSA doubling time 9 to <15 months, HR, 0.580, P<.001).

The risk of death was increased with higher log PSA at baseline (HR, 1.151, P<.0001). Patients who developed metastases were more than three times more likely to die than patients without  metastases (HR, 3.438, P<.001).

“In this study of veteran men with nmCRPC, higher baseline PSA, a shorter PSA doubling time, and the development of metastases were associated with an increase in the risk of death,” the researchers said.

Source: Fuld AD, Young-Xu Y, Li S, et al. Predictors of overall survival (OS) in veterans with non-metastatic castration resistant prostate cancer (nmCRPC). Abstract of study presented in conjunction with the American Society of Clinical Oncology 2018 Annual Meeting, June 2-5, 2018, Chicago, Illinois.