Clinical predictors of upgrading to Gleason grade 4 or 5 disease at radical prostatectomy: potential implications for patient selection for radiation and androgen suppression therapy

Abstract

Purpose: A survival benefit has been suggested by the Radiation Therapy Oncology Group (RTOG) for the addition of androgen suppression to external beam radiation therapy for patients with locally advanced and high-grade disease. This study was performed to identify clinical factors that predicted high-grade disease at prostatectomy (i.e., Gleason grade 4 or 5) in patients with clinically localized and low-grade disease (i.e., Gleason grades 1-3) at biopsy. These pretreatment factors may allow for the identification of patients likely to derive a survival benefit from the addition of androgen suppression to external beam radiation therapy while awaiting the results of the prospective randomized trials.

Methods and materials: Concordance testing of both the primary and secondary biopsy and prostatectomy Gleason grades was performed in 693 patients with clinical Stage T1c, 2 prostate cancer managed with a radical prostatectomy (RP). For the subset of 420 patients with low-grade disease (i.e., Gleason grade < or =3) a logistic regression multivariable analysis was performed to evaluate the ability of the preoperative prostate-specific antigen (PSA), clinical stage, and ultrasound determined prostate gland volume to predict for upgrading to high-grade disease (i.e., Gleason grade 4 or 5).

Results: Forty percent of men with low-grade disease at biopsy were found to have high-grade disease at RP. Men who have at least a 50% chance of being upgraded from biopsy Gleason grade < or =3 to prostatectomy Gleason grade > or =4 disease included those with prostate gland volumes < or =75 cm3 and a PSA > 20 ng/ml or a PSA >10 and < or =20 and clinical Stage T2b,2c. For men with prostate gland volumes >75 cm3, only those with both PSA > 20 ng/ml and clinical Stage T2b,2c were at a significant risk of upgrading.

Conclusion: Until the randomized data become available, clinical factors may be useful in identifying patients with clinically localized prostate cancer who are likely to benefit from combined androgen suppression and external beam radiation therapy.