Association of Prostate-Specific Antigen Velocity With Clinical Progression Among African American and Non-Hispanic White Men Treated for Low-Risk Prostate Cancer With Active Surveillance

Abstract

Importance: The association of prostate-specific antigen velocity (PSAV) with clinical progression in patients with localized prostate cancer managed with active surveillance remains unclear and, to our knowledge, has not been studied in African American patients.

Objectives: To test the hypothesis that PSAV is associated with clinical progression in patients with low-risk prostate cancer treated with active surveillance and to identify differences between African American and non-Hispanic White patients.

Design, setting, and participants: This was a retrospective population-based cohort study using patient records from the Veterans Heath Administration Informatics and Computing Infrastructure on 5296 patients with a diagnosis of localized prostate cancer from January 1, 2001, to December 31, 2015, who were managed with active surveillance. Follow-up extended through March 31, 2020. Low-risk prostate cancer was defined as International Society of Urologic Pathology grade group (GG) 1 clinical tumor stage 2A or lower, PSA level of 10 ng/dL or lower, active surveillance, and no definitive treatment within the first year after diagnosis with at least 1 additional staging biopsy after diagnostic biopsy.

Exposures: Prostate-specific antigen testing.

Main outcomes and measures: The primary outcome was GG progression detected after repeated biopsy or prostatectomy, defined as GG2 or higher or GG3 or higher. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards regression models were used to test associations between PSAV and outcomes.

Results: The final cohort (n = 5296) included 3919 non-Hispanic White men (74.0%; mean [SD] age, 65.7 [5.8] years) and 1377 African American men (26.0%; mean [SD] age, 62.8 [6.6] years). Compared with African American patients, non-Hispanic White patients were older (mean [SD] age, 65.7 [5.8] years vs 62.8 [6.6] years; P < .001), presented with higher cT stage (stage T2, 608 [15.5%] vs 111 [8.1%]; P < .001), had a higher Charlson Comorbidity Index score (1 and ≥2, 912 [23.3%] vs 273 [19.8%]; P = .002), had higher median income ($60 000 to ≥$100 000, 1223 [31.2%] vs 282 [20.5%]; P < .001), and had a higher median level of education (20% to ≥30% with college degree, 1192 [30.4%] vs 333 [24.2%]; P < .001). Progression to GG2 or higher occurred in 2062 patients (38.9%), with a cumulative incidence of 43.2%, and progression to GG3 or higher occurred in 728 patients (13.7%). Fifty-four patients (1.0%) developed metastases. On multivariable analysis, PSAV was significantly associated with progression to GG2 (hazard ratio, 1.32 [95% CI, 1.26-1.39]), GG3 (hazard ratio, 1.51 [95% CI, 1.41-1.62]), and metastases (hazard ratio, 1.38 [95% CI, 1.10-1.74]). Optimal PSAV thresholds that were associated with progression were significantly lower for African American patients (0.44 ng/mL/y) compared with non-Hispanic White patients (1.18 ng/mL/y).

Conclusions and relevance: This study suggests that PSAV is significantly associated with grade progression among patients with low-risk prostate cancer managed with active surveillance, but at lower values for African American patients compared with non-Hispanic White patients. These data suggest that serial PSA measures may potentially substitute for multiple prostate biopsies and that African American patients may merit increased frequency of PSA testing.

Figure 1.. CONSORT Flow Diagram

PSA indicates prostate-specific antigen; VHA, Veterans Health Administration.

Figure 2.. Cumulative Probability of Upgrading

A, Upgrading to grade group (GG) 2 for non-Hispanic White patients. B, Upgrading to GG2 for African American patients. C, Upgrading to GG3 for non-Hispanic White patients. D, Upgrading to GG3 for African American patients. A prostate-specific antigen velocity (PSAV) of 1.18 or less for non-Hispanic White patients or 0.44 or less for African American patients is below the PSAV. A PSAV of greater than 1.18 for non-Hispanic White patients or greater than 0.44 for African American patients is above the PSAV threshold.

Figure 3.. Cumulative Incidence of Metastases for All Patients Stratified by Prostate-Specific Antigen Velocity (PSAV) Threshold

A PSAV of 1.77 or less is below the PSAV threshold. A PSAV of greater than 1.77 is above the PSAV threshold.