Proliferative cell nuclear antigen in postradiotherapy prostate biopsies

Abstract Purpose: To determine if staining for proliferative cell nuclear antigen (PCNA) can distinguish between biologically active and inactive "residual tumor" in postradiotherapy prostate biopsies by correlating PCNA staining with clinical outcome. Methods and Materials: Since July 1990 all patients treated at the General Division of the Ottawa Regional Cancer Center with radical external beam radiotherapy for prostate cancer have had systematic transrectal ultrasound and transrectal ultrasound-guided biopsies beginning 12 months postradiotherapy. One hundred sixty-two patients have had 278 transrectal ultrasounds with four to seven biopsy specimens per examination. All biopsies were stained for prostate specific antigen and prostatic acid phosphatase. Keratin 903 was used to distinguish radiation atypia in benign glands from residual cancer. PCNA staining was done on all suspicious biopsies. Stage distribution was 31 T 1b , 35 T 2a , 61 T 2b , and 35 T 3–4 . Median follow-up was 32 months (range 13–74). Results: Negative biopsies have been obtained in 83% of T 1b and T 2a tumors and 70% of T 2b and T 3–4 . Twenty-six tumors have recurred locally (T 1b : 10%, T 2a : 3%, T 2b : 21%, T 3–4 : 26%), six with concurrent distant metastases. Of these 26 local failures, 23 had positive PCNA (mean 15.4 nuclei per 100) and three could not be determined (insufficient tissue). In 34 patients showing residual carcinoma at the first postradiotherapy biopsy, subsequent negative biopsies were obtained at a median of 25 months. Proliferative cell nuclear antigen staining could be performed in 23 of these 34 patients. Sixty-five percent (1523) were negative on the first biopsy, indicating a nonproliferative state. In those with PCNA positive residual on initial biopsy, none retained PCNA staining on subsequent negative biopsies. One patient with an initial PCNA negative biopsy has failed locally. Conclusion: Proliferative cell nuclear antigen staining is useful in postradiotherapy prostate biopsies. Negative PCNA in a positive biopsy predicts (83–97%) for eventual resolution of tumor. Positive PCNA correlates with local failure (49–79%), but when present in an early biopsy (12–18 months), may still disappear.