African Americans with low-risk prostate cancer saw progression at lower PSAV thresholds

Prostate-specific antigen velocity (PSAV), the rate of change in prostate-specific antigen (PSA) values per year, was significantly associated with clinical progression to more advanced disease in patients with low-risk prostate cancer being managed with active surveillance (AS), a retrospective, population-based cohort study found.

Importantly, however, clinical progression occurred at much lower PSAV values for African American men than it did for non-Hispanic White patients.

In a cohort of 5,296 patients with localized prostate cancer on AS, a higher PSAV was associated with a 32% increased risk of progression to grade group (GG)2 disease (hazard ratio [HR] 1.32 [95% CI, 1.26-1.39; P<0.001]), J. Kellogg Parsons, MD, MHS, Department of Urology, University of California, San Diego, and UC San Diego Moores Comprehensive Cancer Center, La Jolla, California, and colleagues reported in JAMA Network Open.

Similarly, a higher PSAV value was associated with a 51% greater risk of progression to GG3 disease (HR 1.51 [95% CI, 1.41-1.62; P<0.001]), investigators added.

Compared to non-Hispanic White patients, African American patients had a 42% higher risk of progression to GG2 (HR 1.42 [95% CI, 1.26-1.59]) and a 51% greater risk of progression to GG3 disease (HR 1.51 [95% CI, 1.24-1.85]) but African American patients were more likely to progress to higher-grade disease at lower PSAV values.

“To our knowledge, this study is the first to assess PSAV in African American patients undergoing AS, and one of the largest studies yet of PSAV, progression, and AS in patients with localized prostate cancer,” Parsons and colleagues wrote. “…Based on this study, a PSAV threshold of 0.44 ng/mL/y suggests a clinically significant risk of progression for African American patients compared with 1.18 ng/mL/y for non-Hispanic White patients.”

Commenting on the findings, Yaw Nyame, MD, and Michael Porter, MD, both affiliated with the Veterans Affairs Puget Sound Healthcare System, Seattle, Washington, felt that the study was “impressive” in the breadth of its data and in the length of its follow-up of over 7.9 years. However, the editorialists did not share the authors’ conclusion that Black men should have a different cut point for PSAV than White men.

“Historically, nearly 30% of men who met criteria for low-risk disease were reclassified to higher-grade disease at their first prostate biopsy after their initial diagnosis,” Nyame and Porter observed. They also noted that disease upgrading is better observed at surgery due to the pathologists’ ability to sample the entire prostate.

“It would also be important to understand whether these upgrading events occurred at the first biopsy after diagnosis, which would suggest that these men may have had their true disease burden misclassified at their initial biopsy,” the editorialists cautioned.

They also felt it was “unclear” from the study why physicians should approach the management of favorable-risk prostate cancer differentially based on race and PSAV alone.

“A Black man whose PSA increased from 5.0 to 5.44 ng/mL during the course of one year should not be considered unsuitable for continuation of active surveillance,” Nyame and Porter argued. “Such a strategy may unduly increase this patient’s risk of overtreatment [and i]t also highlights the importance of nuance in interpreting PSA parameters in active surveillance, which should also factor in absolute PSA values.”

For the analysis by Parsons et al, the cohort consisted of 74% non-Hispanic White men (mean age 65.7 years) and 26% African American men (mean age 62.8 years) registered with the Veterans Health Administration Corporate Data Warehouse between January 2001 and December 2015.

Men with low-risk prostate cancer who had been managed with AS for at least one year were included in the analysis. Low-risk prostate cancer was defined as men with GG pathology of 1 (Gleason score of 6), clinical tumor stage 2A or lower, and a PSA level of 10 ng/dL or lower.

“The primary outcome was incident disease progression on repeated biopsy or radical prostatectomy, whichever occurred first,” the authors noted, and the secondary outcome was incident metastases.

The mean number of PSA values used for PSAV calculations was approximately 8.67 per patient, and the last PSA level was significantly lower prior to biopsy or prostatectomy in non-Hispanic White patients at a mean of 7.33 ng/dL compared to a mean of 8.35 ng/dL in African American patients (P<0.001).

Notably, however, after controlling for PSAV, the study authors “found that a higher last absolute PSA level was associated with a decreased risk of progression to GG2 (HR, 0.98; 95% CI, 0.97-0.99; P<0.001) and GG3 (HR, 0.98; 95% CI, 0.97-0.99; P=0.002), which suggests that a high but stable PSA level is not strongly associated with grade progression.”

At a mean follow-up of 7.91 years, the cumulative incidence of progression to GG2 pathology or higher was 43.2%, they noted. The risk of metastases at follow-up, on the other hand, was very low at only 1%; however, PSAV was again associated with a 38% increased risk of metastases (HR 1.38 [95% CI, 1.10-1.74; P=0.005]), the authors noted.

This time, no significant difference in the risk of metastases was observed between African American patients and non-Hispanic Whites.

“[G]iven the robustness of PSAV’s association with pathologic upgrading, these data warrant consideration of substituting PSAV for serial prostate biopsies in appropriately selected patients,” the authors suggested.

Transrectal ultrasound-guided prostate biopsies are invasive and can be associated with significant infection risk; thus, obviating the need for serial biopsies would improve care, they noted. African American patients may also benefit from increased frequency of PSA testing, which, when used together with correspondingly lower PSAV thresholds, may better inform clinical decision-making.

In addition, PSAV is also readily determined using online calculators which can be readily accessed in an office-based setting.

  1. The rate of change in PSA values per year or prostate-specific antigen velocity (PSAV) was found to drive clinical progression to more advanced disease in low-risk prostate cancer managed with active surveillance.

  2. PSAV thresholds for higher grade progression were lower for African American patients with low-risk prostate cancer than they were for non-Hispanic White patients.

Pam Harrison, Contributing Writer, BreakingMED™

The study authors and editorialists had no relevant relationships to disclose.

Cat ID: 25

Topic ID: 78,25,730,25,192,73,925