Serum testosterone as a biomarker for second prostatic biopsy in men with negative first biopsy for prostatic cancer and PSA>4ng/mL, or with PIN biopsy result

Abstract Introduction: Data from animal, clinical and prevention studies support the role of androgens in prostate cancer growth, proliferation and progression. Results of serum based epidemiologic studies in humans, however, have been inconclusive. The present study aims to define whether serum testosterone can be used as a predictor of a positive second biopsy in males considered for re-biopsy. Material and Methods: The study included 320 men who underwent a prostatic biopsy in our department from October 2011 until June 2012. Total testosterone, free testosterone, bioavailable testosterone and prostate pathology were evaluated in all cases. Patients undergoing a second biopsy were identified and biopsy results were statistically analyzed. Results: Forty men (12.5%) were assessed with a second biopsy. The diagnosis of the second biopsy was High Grade Intraepithelial Neoplasia in 14 patients (35%) and Prostate Cancer in 12 patients (30%). The comparison of prostatic volume, total testosterone, sex hormone binding globulin, free testosterone, bioavailable testosterone and albumin showed that patients with cancer of the prostate had significantly greater levels of free testosterone (p=0.043) and bioavailable T (p=0.049). Conclusion: In our study, higher free testosterone and bioavailable testosterone levels were associated with a cancer diagnosis at re-biopsy. Our results indicate a possible role for free and bioavailable testosterone in predicting the presence of prostate cancer in patients considered for re-biopsy.

Multiple cores of high grade prostatic intraepithelial neoplasia and any core of atypia on first biopsy are significant predictor for cancer detection at a repeat biopsy

PURPOSE: To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. RESULTS: A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). CONCLUSIONS: Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients.

Clinical features and prognosis of prostate cancer with high-grade prostatic intraepithelial neoplasia

PURPOSE: To evaluate the clinical features and biochemical recurrence (BCR) in prostate cancer (PCa) with high-grade prostatic intraepithelial neoplasia (HGPIN). MATERIALS AND METHODS: We retrospectively analyzed the medical records of 893 patients who underwent a radical prostatectomy for PCa between 2011 and 2012 at Asan Medical Center; 752 of these patients who did not receive neoadjuvant or adjuvant therapy and were followed up for more than 1 year were included. The cohort was divided into two groups-patients with and without HGPIN-and their characteristics were compared. The Cox proportional hazards model was used to analyze factors affecting BCR. RESULTS: In total, 652 study patients (86.7%) had HGPIN. There were no significant differences in preoperative factors between the two groups, including age (p=0.369) and preoperative prostate-specific antigen concentration (p=0.234). Patients with HGPIN had a higher Gleason score (p=0.012), more frequent multiple tumor (p=0.013), and more perineural invasion (p=0.012), but no other postoperative pathologic characteristics were significantly different between the two groups. There were no significant differences in BCR (13.0% vs. 11.5%, p=0.665) and HGPIN was not associated with BCR (p=0.745). In multivariate analysis, only the T stage (p<0.001) was associated with BCR. CONCLUSIONS: PCa patients with HGPIN have a higher Gleason score, more frequent multiple tumors, and more perineural invasion than those without HGPIN. The presence of HGPIN is not an independent predictor of BCR.

How many cores should be taken in a repeat biopsy on patients in whom atypical small acinar proliferation has been identified in an initial transrectal prostate biopsy?

Objective To compare cancer detection rates according to the number of biopsy cores in patients on whom a repeat prostate biopsy was performed for atypical small acinar proliferation (ASAP). Materials and Methods The data of 4950 consecutive patients on whom prostate biopsies were performed were assessed retrospectively. A total of 107 patients were identified as having ASAP following an initial prostate biopsy, and they were included in the study. A six-core prostate biopsy (PBx) was performed on 15 of the 107 patients, 12 PBx on 32 patients, and 20 PBx on 60 patients. Cancer detection rates were compared according to the number of biopsy cores. The localization of the cancer foci was also evaluated. Results The cancer detection rates in patients on whom 6 PBx, 12 PBx, and 20 PBx were performed were 20% (3/15), 31% (10/32), and 58% (35/60), respectively, and a statistically significant difference was found (p = 0.005). When cancer detection rates in patients with total prostate specific antigen (PSA) < 10ng/mL, PSA density ≥ 0.15, normal digital rectal examination, and prostate volume ≥ 55mL were compared according to the number of biopsy cores, a significant difference was identified (p = 0.02, 0.03, 0.006, and 0.04, respectively). Seventy-five percent of the foci where cancer was detected were at the same and/or adjacent sites as the ASAP foci in the initial biopsy, and 54% were identified in contralateral biopsies in which ASAP foci were present. Conclusion As the biopsy core number increases, the cancer detection rate increases significantly in patients on whom a repeat biopsy is performed due to ASAP. The highest cancer rate is found in 20-core repeat biopsies performed equally from all foci. .

Prostate biopsy findings in Indian men: A hospital-based study.

Aims: To review prostatic biopsy findings in Indian patients with elevated serum prostate-specific antigen (PSA) attending the Urology department at a tertiary care hospital. Settings and Design: A retrospective study of 119 patients, who underwent TRUS-guided prostatic biopsy, was conducted. Materials and Methods: A total of 119 patients undergoing TRUS-guided prostatic biopsy were evaluated. Age, presentation, PSA, digital rectal examination, number of cores, and final histology were analyzed. Minimum 10 cores biopsies were performed in 109/119 (92%) and 12 cores in 92/119 (77%). Patients were stratified into three groups based on their PSA: 4-10 ng/ml (group I), 10-20 ng/ml (group II), and >20 ng/ml (group III). Statistical Analysis: Unpaired t-test, Chi-square test, and logistic regression were calculated using an Excel (Ver 2007) and online calculators (P < 0.05 significant). Results: Mean age was 67.6 years. Inflammatory pathology (30/119) was common at all PSA levels. In men with negative DRE and PSA > 10 ng/ml, inflammatory pathology was more likely (Chi 4.2798, P = 0.039). Cancer was found in 29/119 biopsies (group I 2/28, group II 3/45, and group III 24/46). Patients with PSA > 20 ng/ml were more likely to show cancer. Precursor lesions were noted in 10/119 (8.4%). On univariate analysis age, PSA, and DRE all showed significant association with histologic cancer but on multiple logistic regression analysis, only PSA (OR 1.03, P = 0.0021) and DRE (OR 8.07, P = 0.0007) were predictive of cancer. Conclusions: Cancer is less common and inflammatory lesions more common at all levels of PSA in our patients. The effect of antibiotics on PSA and biopsy in our patients needs to be explored.

The implication of initial 24-core transrectal prostate biopsy protocol on the detection of significant prostate cancer and high grade prostatic intraepithelial neoplasia

PURPOSE: To assess the diagnostic value of an initial 24-sample transrectal ultrasound guided (TRUS) prostate biopsy protocol compared to the 10-core technique. MATERIALS AND METHODS: We retrospectively reviewed the prostate biopsy database of consecutive men undergoing prostate biopsies under local anesthesia by using the 10 (Group A) and 24 (Group B) protocols. Men were stratified according to biopsy protocol and PSA levels. Exclusion criteria were age = 75 years and PSA > 20 ng/mL. The Mann-Whitney U and Fisher's exact test were used for statistical analysis. RESULTS: Between April 2007 and August 2009, 869 men underwent TRUS prostate biopsies of which 379 were eligible for the study. Group A (10-cores) consisted of 243 (64.11 percent) men and group B (24-cores) included 139 (35.89 percent) men. The overall prostate cancer detection rate was 39.09 percent and 34.55 percent in Group A and B, respectively (p = 0.43). An overall 9.8 percent increase in Gleason 7 detection rate was found in Group B (p = 0.24). The high-grade prostatic intraepithelial neoplasia (HGPIN) detection rate in men with negative initial biopsies was 15.54 percent and 35.55 percent in Group A and B, respectively (p < 0.001). In patients with PSA < 10 ng/mL, the 24-core technique increased Gleason 7 detection rate by 13.4 percent (p = 0.16) and HGPIN by 23.4 percent (p = 0.0008), compared to the 10 core technique. The 24-core technique increased the concordance between needle biopsy and prostatectomy specimen compared to 10-core technique (p < 0.002). CONCLUSIONS: The initial 24-core prostate biopsy protocol did not show any benefit in the detection of prostate cancer compared to the 10-core technique. However, it improved the HGPIN detection and the correlation between biopsy results and radical prostatectomy Gleason score in men with lower PSA levels.

Serum levels of hypothalamic-pituitary-testicular axis hormones in men with or without prostate cancer or atypical small acinar proliferation

INTRODUCTION: Substantial controversy exists regarding the association between testosterone serum levels and prostate cancer. OBJECTIVE: To evaluate the levels of hypothalamic-pituitary-testicular axis hormones in the sera of men with prostate cancer and atypical small acinar proliferation as well as those with normal biopsies. METHODS: A study cohort of 186 men with suspected prostate cancer who had undergone transrectal prostate biopsies was used in this study. The patients were divided into the following three groups based on the histology of the biopsy samples: no neoplasia, atypical small acinar proliferation or prostate cancer. Demographic data were also collected. Levels of total testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and serum prostate-specific antigen were measured in blood samples. RESULTS: Initially, 123 men were found to be without neoplasia, 26 with atypical small acinar proliferation and 37 with prostate cancer. After a second biopsy was taken from the men diagnosed with atypical small acinar proliferation, the diagnoses were revised: 18 were diagnosed with atypical small acinar proliferation and 45 with prostate cancer. No significant differences between the groups were identified regarding age, smoking history, chronic diseases, body mass index or PSA levels (P >.0.05). The mean serum levels of testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin and estradiol were similar in all of the groups (P >.0.05). Furthermore, in individuals with prostate cancer, the Gleason scores and prevalence of hypogonadism were not significantly different (P.> 0.05). CONCLUSION: The present study revealed no difference in the serum levels of testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin or estradiol in men without neoplasia compared with those with atypical small acinar proliferation or prostate cancer.

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.

Prostate cancer detection at rebiopsy after an initial benign diagnosis: results using sextant extended prostate biopsy

INTRODUCTION: Sextant prostate biopsy remains the standard technique for the detection of prostate cancer. It is well known that after a diagnosis of small acinar proliferation (ASAP) or high grade prostate intraepithelial neoplasia (HGPIN), the possibility of finding cancer is approximately 40 percent and 30 percent, respectively. OBJECTIVE: We aim to analyze follow-up biopsies on patients who initially received a benign diagnosis after exclusion of HGPIN and ASAP. METHODS: From July 2000 to December 2003, 1177 patients were submitted to sextant extended prostate biopsy in our hospital. The mean patient age was 65.5 years old, and the median number of fragments collected at biopsy was 13. HGPIN and ASAP were excluded from our study. We only considered patients who had a diagnosis of benign at the first biopsy and were subjected to rebiopsies up until May 2005 because of a maintained suspicion of cancer. RESULTS: Cancer was initially detected in 524 patients (44.5 percent), and the diagnosis was benign in 415 (35.3 percent). Rebiopsy was indicated for 76 of the latter patients (18.3 percent) because of a persistent suspicion of cancer. Eight cases of adenocarcinoma (10.5 percent) were detected, six (75 percent) at the first rebiopsy. Six patients were submitted to radical prostatectomy, and all tumors were considered clinically significant. CONCLUSION: Our data indicate that in extended prostate biopsy, the first biopsy detects more cancer, and the first, second, and third rebiopsies after an initial benign diagnosis succeed in finding cancer in 7.9 percent (6/55), 5.9 percent (1/15) and 20 percent (1/4) of patients, respectively.

Inflammatory atrophy on prostate needle biopsies: is there topographic relationship to cancer?

INTRODUCTION: Chronic inflammation of longstanding duration has been linked to the development of carcinoma in several organ systems. It is controversial whether there is any relationship of inflammatory atrophy to prostate cancer. It has been suggested that the proliferative epithelium in inflammatory atrophy may progress to high-grade prostatic intraepithelial neoplasia and/or adenocarcinoma. The objective of our study is to compare on needle prostate biopsies of patients showing cancer the topographical relation of inflammatory atrophy and atrophy with no inflammation to adenocarcinoma. MATERIALS AND METHODS: The frequency and extent of the lesions were studied on 172 needle biopsies of patients with prostate cancer. In cores showing both lesions, the foci of atrophy were counted. Clinicopathological features were compared according to presence or absence of inflammation. RESULTS: Considering only cores showing adenocarcinoma, atrophy was seen in 116/172 (67.44 percent) biopsies; 70/116 (60.34 percent) biopsies showed atrophy and no inflammation and 46/116 (39.66 percent) biopsies showed inflammatory atrophy. From a total of 481 cores in 72 biopsies with inflammatory atrophy 184/481 (38.25 percent) cores showed no atrophy; 166/481 (34.51 percent) cores showed atrophy and no inflammation; 111/481 (23.08 percent) cores showed both lesions; and 20/481 (4.16 percent) showed only inflammatory atrophy. There was no statistically significant difference for the clinicopathological features studied. CONCLUSION: The result of our study seems not to favor the model of prostatic carcinogenesis in which there is a topographical relation of inflammatory atrophy to adenocarcinoma.

Significance of apoptosis in prostatic intraepithelial neoplasia and carcinoma.

This study was carried out to assess the significance of apoptosis in prostatic intraepithelial neoplasia (PIN) and prostate cancer. A total of 120 prostatic specimens were studied in the department of Pathology [corrected] JNMC, Aligarh. The rate of apoptosis in PIN and prostate cancer was examined by quantifying the number of apoptotic bodies per hundred cells (apoptotic index) on haematoxylin and eosin stained histological sections [corrected] A significant correlation was noted between increasing apoptotic indices and increasing Gleason grades within a cancer.

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.

Premalignant lesions of prostate and their association with nodular hyperplasia and carcinoma prostate.

BACKGROUND: A relatively new development in the arena of prostatic histopathological study is the premalignant proliferative changes in the glandular epithelium, possibly relating to carcinoma. Two major categories have come up, namely prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). AIMS: The aims of present study were to identify foci of the two putative premalignant conditions viz. PIN and AAH in ducto-acinar lining epithelia of 200 prostatectomy specimens and their association with nodular hyperplasia and adenocarcinoma prostate. MATERIAL AND METHODS: Micro sections from 200 prostatectomy specimens, received in the Department of Pathology, PGIMS, Rohtak, were extensively studied for the presence and association of premalignant conditions. Significant values were obtained by employing Chi-square (chi2) test, with P value < 0.05 as significant. RESULTS: Out of 177 cases of nodular hyperplasia, 53 (29.9%) showed PIN and 38 (20.3%) showed presence of AAH. All 6 cases (100%) of pure carcinoma revealed foci of PIN. Out of the remaining 23 cases of carcinoma with nodular hyperplasia, foci of PIN were observed in 16 cases (94.1%) and AAH in 2 cases (11.7%). High-grade PIN was observed in 20 cases (86.9%) of the total 23 cases of carcinoma, with/without nodular hyperplasia and 20 cases (11.2%) of nodular hyperplasia. Low-grade PIN was observed in 33 cases (18.6%) of nodular hyperplasia and in only 1 case (5.8%) of carcinoma prostate with nodular hyperplasia. CONCLUSION: PIN, especially high-grade type was the most commonly observed premalignant lesion, in cases of adenocarcinoma, thereby suggesting it to be the likely precursor of carcinoma prostate. AAH showed a weaker association with carcinoma.

Patología prostática diagnosticada mediante biopsias en el servicio de anatomía patológica Dr Hans Doehnert del Hospital Central Universitario Antonio María Pineda (HCUAMP) de Barquisimeto durante el año 2000 / Prostatic pathology diagnosed by means of biopsies at the service of pathologycal anatomy Dr Hans Doehnert of the Hospital Central Universitario Antonio María Pineda

Se realizó una revisión de resultados de biopsia entr Enero y Diciembre del año 2000, tipo descriptiva longitudinal retrospectiva con la finalidad de analizar la patología prostática diagnosticada mediante biopsias en el Servicio de Anatomía Patológica Dr Hans Doehnert del Hospital Central Universitario "Antonio María Pineda" de Barquisimeto, para lo cual se seleccionaron 91 resultados con dichos diagnósticos. La patología más frecuente fue la Hiperplasia Prostática Benigna con Inflamación Crónica (39,6 por ciento), seguida de la Hiperplasia Prostática Benigna Aislada (31,8 por ciento), el Adenocarcinoma prostático fue diagnosticado en 9,9 por ciento de los casos. La Hiperplasia Prostática Benigna fue más frecuente entre 61 y 70 años (40 por ciento de los casos) y la prostatitis crónica entre 61 y 70 años (46 por ciento). En un 75,3 por ciento de los casos hubo correlación entre el diagnóstico preoperatorio y los hallazgos histológicos. El adenocarcinoma de próstata fue mas frecuente entre 71 y 75 años (37,5 por ciento), predominando los grados II y IV con un porcentaje de 37,5 por ciento cada uno. En la Neoplasia Intraepitelial Prostática el grado I se presentó con mayor porcentaje (63,6 por ciento)

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