Monitoring of PSA Density Advised During Active Surveillance of Prostate Cancer
Key findings
- Massachusetts General Hospital researchers conducted the first study to correlate progression of prostate cancer during active surveillance with serial measurements of prostate-specific antigen density (PSAD)
- The 453 patients included in the chart review had Gleason grade group 1 disease, ≥2 prostate biopsies, ≥2 imaging-based prostate volume measurements, and ≥2 PSAD measurements at least 1 year apart
- Change in PSAD over time was 21 times greater in patients who exhibited biopsy grade progression than in those whose disease did not progress, and an increase in PSAD was strongly prognostic of progression
- Specifically, patients with PSAD values in the highest quartile, as well as those with a value ≥0.15 ng/mL at any point during surveillance, experienced distinctly reduced progression-free survival
- Routine monitoring of PSAD during active surveillance should be integrated into clinical practice to improve risk stratification, especially because it confers no additional cost
Prostate-specific antigen density (PSAD), the total PSA divided by prostate volume, has long been recognized as a strong prognostic marker of prostate cancer. It has also been associated with the risk of disease progression during active surveillance (AS) when measured at diagnosis or initial confirmatory biopsy.
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Adam S. Feldman, MD, MPH, surgical program director of the Genitourinary (GU) Oncology Program at Massachusetts General Hospital and chief of Urologic Oncology at Mass General Brigham, Andrew Gusev, MD, a clinical fellow in the Department of Surgery, and colleagues, conducted the first study aimed at correlating serial PSAD measurements with progression of prostate cancer during AS.
In Urologic Oncology: Seminars and Original Investigations, they report that PSAD retains significant prognostic value after diagnosis. Even more than measuring PSA alone, measuring PSAD throughout AS can strengthen currently available risk stratification tools.
Methods
Patients were included in the retrospective study if they began AS for prostate cancer at Mass General between 1997 and 2016 and had Gleason grade group (GG) 1 disease, ≥2 prostate biopsies, ≥2 prostate volume measurements with radiological imaging, ≥2 PSA values during AS, and at least 1 year of surveillance between their first and last PSAD measurement.
The AS protocol, formalized in 2008, includes PSA and digital rectal exam every 6 months for 3 years, then annually when clinically indicated. Confirmatory biopsy is mandatory between 12 to 18 months. Multiparametric MRI and additional surveillance biopsies are done at the discretion of the physician and patient.
PSAD and Risk of Progression
453 men were included in the study, median follow-up time 5.9 years. 137 men (30%) had biopsy grade progression during AS, defined as GG ≥2. The others had a stable grade at their last surveillance biopsy.
As might be expected, but never before demonstrated, patients who experienced biopsy grade progression had significantly higher PSAD levels during AS than patients whose disease did not progress. They also had:
- 2 times greater PSA velocity (change in PSA over time): 0.53 vs. 0.24 ng/mL/year (P<0.001)
- 3 times greater PSAD velocity (change in PSAD over time): 0.0085 vs. 0.0004 ng/mL2/year (P<0.001)
Prognostic Markers
Adding serial PSA-derived variables improved the power of Cox regression prognostic models:
- Base model (age, maximum core involvement, fraction of positive cores, National Comprehensive Cancer Network risk level)—concordance index, 0.68
- Base model plus PSAD at diagnosis—c-index, 0.69
- Base model plus serial PSA—c-index, 0.72
- Base model plus serial PSAD or serial PSAD quartiles—c-index, 0.75
After adjustment for baseline characteristics, serial PSAD was the variable that most increased the risk of progression (all P<0.001), whether measured as:
- A continuous variable—HR, 2.01 (P<0.001) per standard deviation increase in PSAD of 0.099 ng/mL/mL during AS
- A binary variable—HR, 3.70 for a PSAD value ≥0.15 ng/mL2 at any point during AS, compared with lower values
- Quartiles—HR, 4.25 (P<0.001) for the highest quartile of PSAD (0.16–1.18 ng/mL2), compared with the lowest quartile (0–0.07 ng/mL2)
Importantly, the progression-free survival of patients who had PSAD values in the lowest quartile was between that of patients whose PSAD values were in the second and third quartiles. Thus, a very low PSAD during AS doesn’t preclude biopsy grade progression.
Routine PSAD Monitoring Is Prudent
Urologists should recalculate PSAD during AS using the most current imaging-determined prostate volume, as that volume can change over time. Patients whose PSAD is low and stable could be considered for less frequent visits (e.g., annual instead of semiannual). A rising PSAD might prompt more frequent visits and perhaps a shorter interval before repeating MRI and biopsy.
A PSAD value ≥0.15 ng/mL2 at any time during AS, or an increase in PSAD values over time, should prompt scrutiny and repeat biopsy.
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