The impact of metformin use on the risk of prostate cancer after prostate biopsy in patients with high grade intraepithelial neoplasia

ABSTRACT Purpose We report our experience on metformin use in diabetic patients and its impact on prostate cancer (PCa) after a high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosis. Materials and Methods We retrospectively analyzed 551 patients with a diagnosis of HGPIN without PCa in a first prostate biopsy. The cohort of the study consisted of 456 nondiabetic subjects, and 95 diabetic patients. Among the patients with diabetes 44 were treated with metformin, and 51 with other antidiabetic drugs. A transrectal ultrasound prostate biopsy scheme with 22 cores was carried out 4-6 months after the first diagnosis of HGPIN. Results Among 195 (35.4%) patients with cancer, there were statistically significant differences in terms of PCa detection (p<0.001), Gleason score distribution (p<0.001), and number of positive biopsy cores (p<0.002) between metformin users and non-users. Metformin use was associated with a decreased risk of PCa compared with neveruse (p<0.001). Moreover, increasing duration of metformin assumption (≥2 years) was associated with decreasing incidence of PCa and higher Gleason score ≥7 compared with assumption <2 years. Conclusions This preliminary experience suggests that metformin use may have some beneficial effects in patients with diabetes and HGPIN; metformin should not be overlooked in these patients because it is neither new nor expensive.

Características histopatológicas de la neoplasia intraepitelial prostática / Histopathologic characteristics of the prostatic intraepithelial neoplasia

La enfermedad de la próstata es hoy un problema de salud por su elevada morbilidad y mortalidad en adultos mayores de 50 años. Acerca de ello se realizó este estudio descriptivo y transversal sobre los hallazgos histopatológicos de neoplasia intraepitelial prostática en las biopsias de próstata útiles, recibidas para su análisis en el Departamento de Anatomía Patológica del Hospital Clinicoquirúrgico Docente Dr Ambrosio Grillo Portuondo de Santiago de Cuba durante el bienio 2008-2009. Entre los principales resultados sobresalió la confirmación, por la mencionada vía, de hiperplasia fibroadenomatosa de la próstata, lesiones prostáticas, carcinomas y otras alteraciones en esa glándula masculina. Los datos obtenidos ratificaron que el diagnóstico a través de muestras de tejido de neoplasia intraepitelial prostática, constituye una de las formas en que los patólogos pueden contribuir a la oportuna detección del carcinoma prostático.

The prostate disease is a health problem nowadays due to its high morbidity and mortality in adults older than 50 years. Based on this, a descriptive and cross sectional study was carried out on the histopathologic findings of the prostatic intraepithelial neoplasia in the useful prostate biopsies examined in the Pathology Department of Dr Ambrosio Grillo Portuondo Clinical Surgical Teaching Hospital in Santiago de Cuba during the biennium 2008-2009. Among the main results there were: the confirmation of prostate fibroadenomatous hyperplasia, prostatic lesions, carcinomas and other alterations in that male gland, all through biopsy. The obtained data confirmed that the diagnosis through samples from the prostatic intraepithelial neoplasia tissue, constitutes one of the ways by which pathologists can contribute to the opportune detection of the prostatic carcinoma.

Vascular endothelial growth factor (VEGF) and prostate pathology

PURPOSE: Previous studies suggest that vascular endothelial growth factor (VEGF) circulating levels might improve identification of patients with prostate cancer but results are conflicting. Our aim was to compare serum VEGF levels across different prostate pathologies (including benign prostatic hyperplasia, prostatitis, high grade prostate intraepithelial neoplasia and prostate cancer) in patients at high risk of prostate cancer. MATERIALS AND METHODS: We consecutively enrolled 186 subjects with abnormal digital rectal examination and/or total PSA (tPSA) = 2.5 ng/mL. Blood was collected before diagnostic ultrasound guided trans-rectal prostate biopsy, or any prostate oncology treatment, to measure PSA isoforms and VEGF. Unconditional logistic regression was used to compute age-, tPSA- and free/total PSA-adjusted odds ratios (OR) and respective 95 percent confidence intervals (95 percent CI) for the association between serum VEGF and different prostatic pathologies. RESULTS: Prostate biopsy main diagnoses were normal or benign prostatic hyperplasia (27.3 percent), prostatitis (16.6 percent), and prostatic cancer (55.0 percent). The median VEGF levels (ng/mL) in these groups were 178.2, 261.3 and 266.4 (p = 0.029), respectively, but no significant differences were observed for benign vs. malignant pathologies (215.2 vs. 266.4, p = 0.551). No independent association was observed between VEGF (3rd vs. 1st third) and prostate cancer, when compared to benign conditions (adjusted OR = 1.44; CI 95 percent: 0.64-3.26). CONCLUSIONS: In patients at high risk of prostate cancer, circulating VEGF levels have no clinical role in deciding which patients should be submitted to prostate biopsy. Prostatitis patients, often with higher PSA levels, also present high serum levels of VEGF, and their inclusion in control groups might explain the heterogeneous results in previous studies.

Repeat prostate biopsies following diagnoses of prostate intraepithelial neoplasia and atypical small gland proliferation

OBJECTIVE: To assess the incidence of diagnosis of high-grade intraepithelial neoplasia or prostate intraepithelial neoplasia (PIN), and atypical small gland proliferation (ASAP) at a uropathology reference center. To assess the indexes and findings on repeat biopsies. MATERIALS AND METHODS: Diagnoses of PIN, ASAP or PIN + ASAP established between January 1, 2001 and December 31, 2003 were searched in our database. We studied repeat biopsies performed up to August 31, 2004. RESULTS: Of 1420 biopsies, ASAP was diagnosed in 26 (1.8 percent) patients, PIN in 142 (10 percent) and PIN + ASAP in 40 (2.8 percent). Repeat biopsies were performed in 98 patients, 16 (61.5 percent) with ASAP, 53 (37.3 percent) with PIN and 29 (72.5 percent) with PIN + ASAP. Carcinoma was diagnosed in 7 cases (43.8 percent) following a diagnosis of ASAP, 12 (41.4 percent) of PIN + ASAP and 7 (13.2 percent) of PIN. The mean interval between repeat biopsies was 299.6 days. There was no difference between groups where cancer was or was not diagnosed on repeat biopsy in relation to age and serum PSA levels. CONCLUSION: Despite explicit recommendations of repeat biopsy on pathology reports and the high incidence of adenocarcinoma on repeat biopsy, re-intervention rates following a diagnosis of PIN, ASAP, PIN + ASAP are low in our setting. The diagnosis that most frequently led to repeat biopsy was PIN + ASAP. Adenocarcinoma was most often diagnosed after the initial diagnosis of ASAP.

Neoplasia intraepitelial prostatica: interpretación diagnóstica / Prostatic intraepithelial neoplasia: dianostic interpretation

De las lesiones conocidad como premalignas la neoplasia intraepitelial prostática (PIN), es la que adquiere mayor relevancia, debido a su estrecha asociación con el cáncer invasor de proóstata. Su incidencia en hombres menores de 60 años ha sido probada y justifica las punciones repetidas en aquellos pacientes que la presenten. En este trabajo se realiza un análisis de 937 biopsias de próstata, y se correlaciona el hallazgo de PIN en sus diferentes grados con el comportamiento del antígeno prostático específico (PSA), la edad del paciente y la existencia de cáncer de próstata