Higher PSA density linked to biopsy progression of prostate cancer

San Francisco-Higher PSA density at diagnosis is associated with biopsy progression of low-risk prostate cancer in patients enrolled in active surveillance.

That finding comes from nearly 5 years of follow-up of 758 men who chose active surveillance at a single institution, reported first author Christopher J. Welty, MD, MS, at the Genitourinary Cancers Symposium in San Francisco.

Men with low-risk prostate cancer and higher PSA density require closer monitoring, and although they still may be able to delay treatment for a number of years, “They are more likely to be treated in the future than if they have a lower PSA density. PSA density was the strongest predictor for upgrade by biopsy and progression to treatment,” said Dr. Welty, a clinical fellow in urology at the University of California, San Francisco, working with Peter R. Carroll, MD, MPH, and colleagues.

Active surveillance relies on accurate risk stratification for effective counseling and involves regular evaluation of factors associated with disease progression in men with low-risk prostate cancer. Dr. Carroll and colleagues have enrolled some 1,009 men on active surveillance, 758 of whom consented to be part of this research. Of these, 68% met UCSF’s strict criteria for selection of active surveillance. These criteria are: stage ≤cT2, PSA <10.0 ng/mL, Gleason score ≤3+3, ≤33% of positive diagnostic core biopsies, and ≤50% single core positive. Some men who did not meet eligibility criteria yet still chose active surveillance were followed as well.

Surveillance consisted of quarterly PSA testing, reimaging with transrectal ultrasound, and annual prostate biopsy. Biopsy progression of disease was defined as an upgrade to Gleason score ≥7 or an increase in volume to at least 33% positive cores.

Mean age at entry was 62 years and 79% of the cohort was Caucasian. The median PSA at diagnosis was 5.3 ng/mL, the median prostate volume was 36 cc, and the median PSA density was 0.13. Two-thirds of the men were stage T1 and 34% were T2. The biopsy Gleason grade was 2 to 6 in 92%. A median of 13 biopsy cores were taken and a median of 13% were positive. At diagnosis, 84% were low and 16% were intermediate CAPRA (Cancer of the Prostate Risk Assessment) clinical risk.

After a median follow-up of 57 months, the men had an average of three biopsies each. The 5-year treatment-free survival was 60%. Of those who went on to active treatment, 65% underwent radical prostatectomy, 24% had radiation, and 11% had androgen deprivation therapy. The 5-year disease-specific survival was 100%.

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Progression-free rate falls with greater PSAD

About half (52%) of the patients progressed by biopsy grade or volume. Sixty-three percent with PSA density <0.15 were biopsy progression free compared with 32% with a PSA density ≥0.15 (p<.01). Active treatment-free survival was 66% in men with a PSA density <0.15 compared with 49% with a PSA density ≥0.15 (p<.01).

Independent factors associated with time to biopsy progression and delayed active treatment were later year of diagnosis, high PSA density at diagnosis, and fewer biopsies.

“In terms of counseling men who are enrolling in active surveillance, PSA density is something to talk about when you’re determining what their likelihood of treatment is in the future,” said Dr. Welty.

He said he believes that PSA density by itself should not be used to recommend treatment in men who enroll in active surveillance, “but perhaps to identify those who need closer monitoring. Other types of tests, such as molecular tests, may be helpful as well,” he added.UT

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