Histopathologic Effects of Three-Dimensional Conformal External Beam Radiation Therapy on Benign and Malignant Prostate Tissues

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Abstract
We reviewed 137 prostate sextant needle biopsies from 137 patients obtained at a median of 35.7 months after three-dimensional conformal external beam radiation therapy (3DCRT). Thirty-one patients (23%) received 3 months of androgen deprivation therapy (ADT) before 3DCRT. We also retrospectively reviewed and assigned a combined Gleason score to the pre-3DCRT needle biopsies (97 patients) or transurethral resection of the prostate gland (1 patient). High-molecular-weight cytokeratin (34βE12) and prostate-specific antigen (PSA) immunohistochemistry was performed in select cases. After 3DCRT, histopathologic changes in benign prostate gland consisted of glandular atrophy, cytologic atypia, and basal cell prominence. The benign glands showed intensely positive reactions with antibodies to high-molecular-weight cytokeratin (34βE12) and negative to weakly positive reactions to PSA. Paneth cell–like change was seen in 44 (32%) of the biopsies, mucinous metaplasia in 29 (21%), luminal blue-tinged mucinous secretions in 14 (10%), and squamous metaplasia in 8 (6%). The changes in benign prostate tissues were similar between patients treated with ADT and 3DCRT and those treated with 3DCRT alone. After 3DCRT, we recognized two histologic patterns of prostate cancer: (1) prostate cancer showing radiation therapy (RT)-related changes characterized by PSA-positive/34βE12-negative poorly formed glands or individual cells with abundant clear to finely granular cytoplasm, and (2) prostate cancer showing no apparent RT effect. High-grade prostatic intraepithelial neoplasia (PIN) was seen in 12 post-3DCRT biopsies (8.8%). The use of neoadjuvant ADT had a significant impact on the results of post-RT biopsy. Of the 31 patients treated with neoadjuvant ADT and 3DCRT, 3 (10%) had post-3DCRT biopsies showing prostate cancer without RT effect compared to 44 of 106 men (41%) treated with 3DCRT alone (p = 0.004). Compared to the Gleason score pre-RT, the Gleason score of cancers showing no RT effect was the same in 25 patients (71%), ±1 point in 8 patients (23%), and +2 points in 2 patients (6%). The mean combined Gleason score post-RT was slightly, although significantly, higher than that pre-RT (7.29 ± 0.71 versus 7.00 ± 0.59, p = 0.01). Serum PSA at the time of post-3DCRT biopsy correlated with biopsy results. Prostate cancer without therapy effect was seen in only one of 43 patients (2%) with a serum PSA level ≤1 ng/ml compared to 46 of 94 patients (49%) with a PSA level >1 ng/ml (p = 0.0001). After 3DCRT, benign prostate glands show profound histopathologic changes and may be confused with prostate cancer. The effects of 3DCRT on prostate cancer are variable, with some cases showing profound therapy-related changes and others showing no apparent therapy effect.

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