Smaller prostates in men with low risk prostate cancer (PCa) may indicate a greater likelihood of harboring tumors of higher grade than indicated by prostate biopsy, according to investigators.

In a study of 1,251 patients undergoing radical prostatectomy for low risk PCa, researchers found that those with smaller prostates had a higher risk of Gleason score upgrades upon examination of the surgical specimen.

The implications of identifying patients at high risk for Gleason score upgrading are “profound,” the researchers reported in The Journal of Urology (2011;186:2221-2227), noting that patients, urologists, and radiation oncologists base treatment plans on patient risk strata, of which biopsy Gleason scores are an important part.

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“The ability to distinguish patients at high risk for upgrading may help patients and clinicians determine patient eligibility for treatment options such as active surveillance and brachytherapy,” the authors wrote. “Thus, the ability to predict upgrading is most relevant in patients with low risk disease.”

Additionally, the findings suggest that cancers in smaller and larger prostates may be biologically different, or that PCa in men with a larger prostate gland may be detected at a more favorable time point in the disease course because of the higher PSA associated with larger prostates, the researchers concluded. Further, the higher PSA density associated with smaller prostates predicts worse disease parameters and prognosis.

For the study, a team led by Daniel A. Barocas, MD, MPH of Vanderbilt University Medical Center in Nashville, Tenn., divided subjects into three groups according pathological Gleason score: no upgrade, minor upgrade (3 + 4 = 7), and major upgrade (4 + 3 = 7 or higher) from a biopsy Gleason score of 6 or less.

Of the 1,251 patients, 387 (31%) were upgraded upon pathological examination of the surgical specimen, including 324 (26%) with minor upgrading and 63 (5%) with major upgrading, Dr. Barocas and colleagues reported.

Men who had no Gleason score upgrade had a median prostate volume of 47 cm3, which was significantly larger than the prostate volumes of patients who had minor and major upgrades (both 43 cm3). Larger prostate size was associated with a 42% and 33% decreased likelihood of any upgrade and major upgrade, respectively, after adjusting for age, surgery year, clinical stage, PSA level, and other potential confounders.

Men with prostate volumes in the 25th percentile (36 cm3) were 50% more likely to have upgrading than men with prostate volumes in the 75th percentile (58 cm3).

For the study, Dr. Barocas’ team used the weight of the surgical specimen as a surrogate for clinical prostate volume. They chose this method because many biopsies were performed by referring urologists and prostate volumes as determined by transrectal ultrasound were not universally available and biopsies were not performed according to a uniform protocol, they noted.

The study population was 92% white and had a median PSA level of 5 ng/mL before surgery.