Diffusion-weighted imaging of the prostate: should we use quantitative metrics to better characterize focal lesions originating in the peripheral zone?

PURPOSE: To compare inter-reader concordance and accuracy of qualitative diffusion-weighted (DW) PIRADSv2.0 score with those of quantitative DW-MRI for the diagnosis of peripheral zone prostate cancer. MATERIALS AND METHODS: Two radiologists independently assigned a DW-MRI-PIRADS score to 92 PZ-foci, in 74 patients (64.3±5.6 years old; median PSA level: 8 ng/ml, normal DRE in 70 men). A standardised ADCmean and nine ADC-derived parameters were measured, including ADCratios with the whole-prostate (WP-ADCratio) or the mirror-PZ (mirror-ADCratio) as reference areas. Surgical histology and MRI-TRUS fusion-biopsy were the reference for tumours and benign foci, respectively. Inter-reader agreement was assessed by the Cohen-kappa-coefficient and the intraclass correlation coefficient (ICC). Univariate-multivariate regressions determined the most predictive factor for cancer. RESULTS: Fifty lesions were malignant. Inter-reader concordance was fair for qualitative assessment, but excellent for quantitative assessment for all quantitative variables. At univariate analysis, ADCmean, WP-ADCratio and WL-ADCmean performed equally, but significantly better than the mirror-ADCratio (p<0.001). At multivariate analysis, the only independent variable significantly associated with malignancy was the whole-prostate-ADCratio. At a cut-off value of 0.68, sensitivity was 94-90 % and specificity was 60-38 % for readers 1 and 2, respectively. CONCLUSION: The whole-prostate-ADCratio improved the qualitative inter-reader concordance and characterisation of focal PZ-lesions. KEY POINTS: • Inter-reader concordance of DW PI-RADSv2.0 score for PZ lesions was only fair. • Using a standardised ADCmean measurement and derived DW-quantitative parameters, concordance was excellent. • The whole-prostate ADCratio performed significantly better than the mirror-ADCratio for cancer detection. • At a cut-off of 0.68, sensitivity values of WP-ADCratio were 94-90 %. • The whole-prostate ADCratio may circumvent variations of ADC metrics across centres.

Tumor target volume for focal therapy of prostate cancer-does multiparametric magnetic resonance imaging allow for a reliable estimation?

PURPOSE: We determined whether endorectal multiparametric magnetic resonance imaging at 1.5 Tesla could predict tumor target volume in the perspective of focal therapy of prostate cancer. MATERIALS AND METHODS: A total of 84 consecutive patients underwent multiparametric magnetic resonance imaging before radical prostatectomy. The volume of each suspicious area detected on magnetic resonance imaging and of all surgical histological foci was determined by planimetry. We first used each magnetic resonance imaging sequence (T2-weighted, diffusion weighted and dynamic contrast enhanced) and then the sequence showing the largest tumor area (multiparametric volume). Finally, the largest area of any sequence was used to calculate a target volume according to the volume of a cylinder. Agreement between magnetic resonance imaging and pathological findings was assessed by linear regression and residual analysis. RESULTS: Histology revealed 99 significant tumors with a volume of greater than 0.2 cc and/or a Gleason score of greater than 6. Of the tumors 16 (16.2%) were undetected by multiparametric magnetic resonance imaging. Linear regression analysis showed that tumor volume estimated by T2-weighted or diffusion weighted imaging correlated significantly with pathological volume (r(2) = 0.82 and 0.83, respectively). Residuals from diffusion weighted imaging volume estimations did not significantly differ from 0. Nevertheless, diffusion weighted imaging underestimated pathological volume in 43 of 87 cases (49%) by a mean of 0.56 cc (range 0.005 to 2.84). Multiparametric and target volumes significantly overestimated pathological volume by a mean of 16% and 44% with underestimation in 28 (32%) and 15 cases (17%), respectively. Volume underestimation was significantly higher for tumor foci less than 0.5 cc. The percent of Gleason grade 4 did not influence tumor volume estimation. CONCLUSIONS: Magnetic resonance imaging can detect most significant tumors. However, delineating a target volume may require further adjustment before planning magnetic resonance imaging targeted focal treatment.

Updating the prostate cancer risk indicator for contemporary biopsy schemes.

INTRODUCTION AND OBJECTIVE: The prostate cancer risk indicator is a validated tool for predicting the chance of a screen detected prostate cancer to be classified as indolent, partially based on lateralized sextant biopsies. Our objective is to extract correction factors for adjustment of the model, addressing contemporary extended biopsy schemes. MATERIALS AND METHODS: Post-mortem 18-core biopsy results of men who died of unrelated causes, but were diagnosed with prostate cancer post-mortem were used to provide details on prostate biopsies and whole mount specimens. For each of the 18-core biopsies showing cancer, Gleason score, number of positive cores, location in the gland and percentage of cancer involvement were determined and correlated to final pathology. Total length of cancer tissue in a 6-core scheme was related to the length in 12 and 18-core schemes to compute correction factors. Furthermore, upgrading on extended biopsies and final pathology was evaluated. RESULTS: Data from 33 autopsied men were included. The 18 and 12-core biopsies showed 192.72 mm and 143.76 mm of prostate cancer, compared to 70.80 mm with lateralized sextant biopsy, resulting in correction factors of 2.72 and 2.03 for 18 and 12-core schemes respectively. Upgrading in Gleason score on extended biopsy regimens compared to lateralized sextant biopsy occurred in 33% (11/33) of the cases. CONCLUSION: Based on autopsy data, the present correction factors provide a support in the adjustment of the prostate cancer risk indicator towards more extended contemporary biopsy schemes, eventually leading to a more accurate prediction of the probability of indolent cancers and assisting patients and clinicians to make appropriate choices in daily practice.

Surgical management of BPH in patients on oral anticoagulation: transurethral bipolar plasma vaporization in saline versus transurethral monopolar resection of the prostate.

INTRODUCTION: To compare postoperative outcomes of patients on oral anticoagulation (OA) treated with transurethral plasma vaporization of the prostate in saline water (TUVis) and transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Between January and December 2009, 111 patients on OA therapy were treated with either TURP or TUVis in eight centers. Types of OA and perioperative management were collected. Postoperative outcomes were statistically compared between the two groups. RESULTS: A total of 57 (51%) and 54 (49%) patients were treated with TURP and TUVis, respectively. Types of OA were not significantly different between the two groups, but bladder catheterization prior to surgery was more frequently observed in the TUVis group. Before surgery, 28 patients were treated with warfarin alone, 74 with a platelet aggregation inhibitor (PAI) alone, and 9 with a combination of both. PAI was withdrawn preoperatively in 50 patients. All treatments with warfarin were switched for heparin. Comparison of the two groups showed significantly less hemorrhagic complications after TUVis. Patients treated with TUVis experienced less bladder washouts (2% versus 18%, p = 0.008), less late hematuria (4% versus 19%, p = 0.02), and lower decrease of serum hemoglobin (mean decrease of 0.66 versus 1.47 g/dL, p = 0.02). Postoperative bladder catheterization and hospital stay were significantly shorter, whereas the rate of urinary retention was significantly higher. Three months after surgery, functional results were not significantly different between the two groups. CONCLUSIONS: In patients on OA, TUVis led to significantly less bleeding, as well as shorter bladder catheterization and hospital stay than TURP.

Pathological characteristics of prostate cancer in elderly men.

PURPOSE: Recent guidelines recommend that men older than 75 years should not be screened for prostate cancer. However, increased life expectancy and the development of less invasive treatments have led to an interest in characterizing prostate cancer in elderly men. We determined how prostate cancer pathological characteristics differ in men older vs younger than 70 years. MATERIALS AND METHODS: We studied differences in prostate cancer pathological characteristics in autopsied glands from men 70 years old or older and compared findings to those in men younger than 70 years. All men died of causes unrelated to prostate cancer. Prostates were whole mounted at 4 mm intervals. Histological analysis was done to identify and characterize each cancer focus observed. Tumor volume was measured by computerized planimetry. Cancer was defined as clinically significant or insignificant based on established histological characteristics. RESULTS: Of 211 prostates evaluated 74 were from men 70 years old or older. We identified cancer in 33 men (45%) in this age group vs in 26 of 137 (19%) younger than 70 years (p <0.001). Men older than 70 years had significantly larger cancer and more clinically significant cancer (64% vs 23%, p <0.005). Older men had more advanced stage cancer and greater Gleason scores (p <0.001). CONCLUSIONS: In an autopsy study of men with no history of prostate cancer those older than 70 years were more likely to have larger and higher grade prostate cancer than younger men.

Saturation biopsies on autopsied prostates for detecting and characterizing prostate cancer.

OBJECTIVES: To evaluate a 36-core saturation biopsy scheme on autopsied prostate glands to estimate the detection rate based on the true cancer prevalence, and to compare the cancer features on biopsy with whole-mount pathological analysis, as saturation biopsies have been proposed as a tool to increase the prostate cancer detection rate, and as a staging tool to identify potentially insignificant cancers before surgery. MATERIAL AND METHODS: We took 36-core needle biopsies in 48 autopsied prostates from men who had no history of prostate cancer. The first 18 cores corresponded to an extended biopsy protocol including six cores each in the mid peripheral zone (PZ), lateral PZ and central zone. Six additional cores were then taken in each of these three locations. We compared the histological characteristics of step-sectioned prostates with the biopsy findings. Tumours were considered clinically insignificant if they were organ-confined with an index tumour volume of <0.5 mL and Gleason score of

Hybrid tumour 'oncocytoma-chromophobe renal cell carcinoma' of the kidney: a report of seven sporadic cases.

OBJECTIVES: To determine whether renal hybrid tumours (HT) appear as a specific clinical and radiological entity, as HT are characterized by the association of both oncocytes and chromophobe cells within the same tumour, and have been described in patients with oncocytosis and Birt-Hogg-Dube syndrome. PATIENTS AND METHODS: We reviewed the medical charts of 67 patients who had a partial or radical nephrectomy in our institution for renal oncocytoma (RO, 24), chromophobe renal cell carcinoma (CRCC, 36) and HT (seven), from January 2006 to October 2007. We report the clinical, radiological and pathological characteristics of the seven cases of HT. RESULTS: The mean (range) age of the patients was 56 (41-68) year. None of the seven patients had any suspicion of RO, based on computed tomography (CT). Two patients had a history of kidney cancer. Five patients had partial and two a radical nephrectomy. The mean (range) maximum tumour diameter was 5.5 (1.8-9) cm. Two tumours were pT1a, two were pT1b and three were pT2. Pathological analysis showed RO-like and CRCC-like cells intermixed (six patients) or distinct (one). After a median (range) follow-up of 20 (8-25) months, none of the patients had any evidence of disease recurrence. CONCLUSIONS: In a large series of patients with sporadic RO and CRCC, 10% of the tumours had hybrid morphological features, as described in oncocytosis and Birt-Hogg-Dube syndrome. We were unable to identify any specific clinical characteristic. Most importantly, none of these HT showed any of the radiological characteristics of RO.

Conformal radiotherapy for detectable PSA following radical prostatectomy: efficacy and predictive factors of recurrence.

INTRODUCTION: Many studies have analyzed outcomes following salvage radiation therapy (RT) after biochemical recurrence--defined as the presence of detectable serum prostate-specific antigen (PSA)--following radical prostatectomy (RP). However, the management of patients with detectable PSA following RP, which is not specific for tumor recurrence, is a matter of debate. This study aimed to evaluate oncological results of three-dimensional conformal RT (3D-CRT) in patients who had biochemical recurrence. MATERIALS AND METHODS: The study included patients who underwent RP, who had a postoperative PSA level--determined between 2 and 4 months after surgery--that was greater than 0.1 ng/ml, and who subsequently received monotherapy with 3D-CRT on the prostate bed. The patients' clinical, characteristics and the pathological characteristics of their biopsy specimens were recorded. The main endpoint was biochemical failure after 3D-CRT, defined as three consecutive elevated PSA levels. RESULTS: The tumors in the 46 patients included 4 (9%) pT2a, 7 (15%) pT2b, 14 (30%) pT2c, 10 (22%) pT3a, 10 (22%) pT3b, and 1 (2%) pT4 tumor. The Gleason score was 7 or higher in 37 patients (80%). Positive surgical margins were seen in 37 patients (80%). The patients had a median postoperative PSA level of 0.29 ng/ml (range, 0.1-5.8 ng/ml) and a median PSA doubling time (PSADT) before RT of 6 months (range, 1-53 months). The rate of biochemical recurrence free survival after 3D-RT was 66% at 30 months. Preoperative PSA, PSADT before RT, and D'Amico scores were significantly associated with biochemical failure after 3D-CRT (p < 0.05). CONCLUSIONS: In cases of persistent PSA following RP for prostate cancer, 3D-CRT can be used as monotherapy with a significant chance of recurrence free survival. Preoperative PSA, PSADT before RT, and D'Amico score are predictive factors of recurrence following RT.

Evaluation of prostatitis in autopsied prostates--is chronic inflammation more associated with benign prostatic hyperplasia or cancer?

PURPOSE: Chronic inflammation is associated with prostate cancer and benign prostatic hyperplasia. However, the prevalence of chronic inflammation in malignant and benign glands has not been compared. We evaluated the association of inflammation, benign prostatic hyperplasia and cancer in autopsied prostates. MATERIALS AND METHODS: We prospectively analyzed 167 autopsied prostates. Pathological analysis identified each focus of cancer, benign prostatic hyperplasia nodules and areas of acute or chronic inflammation. Any cancer focus or benign prostatic hyperplasia nodule involved directly with inflammation was recorded. The association of the prevalence of prostate cancer, benign prostatic hyperplasia and inflammation was statistically assessed. RESULTS: Inflammation was present in 113 (67.6%) of 167 cases. Chronic inflammation was identified in 88 (53%), acute inflammation in 6 (4%), and chronic inflammation and acute inflammation in 19 (11%) glands. In the majority of cases inflammation was present in the transitional zone. A total of 93 glands (56%) were involved with benign prostatic hyperplasia and 49 (29%) with cancer. Of the glands harboring benign prostatic hyperplasia 75% were also involved with chronic inflammation compared to only 50% of those without benign prostatic hyperplasia (p <0.01). Comparatively the glands with or without any evidence of cancer were similarly involved with chronic inflammation (55% vs 58%, p >0.1). Of the 27 glands involved with cancer and benign prostatic hyperplasia, chronic inflammation was more associated with benign prostatic hyperplasia than cancer (p = 0.006). Acute inflammation was not significantly associated with either benign prostatic hyperplasia or cancer. CONCLUSIONS: Chronic inflammation was a common finding in autopsied prostates. It appeared to be directly associated with the presence of benign prostatic hyperplasia but not with cancer.

Occult prostate cancer effects the results of case-control studies due to verification bias.

BACKGROUND: Epidemiological studies of prostate cancer (PCA) which are based on case control comparisons may be effected by verification bias. Verification bias exists when the experimental group has verified PCA, while the control group is presumed to be cancer free, but this is not histologically verified. MATERIALS AND METHODS: Review of the literature and our recent experience with case-control studies of PCA in an autopsy model. RESULTS: When autopsied prostates were evaluated for cancer based on prostatic specific antigen <4 ng/ml, negative biopsy or both criteria, the contamination rate was 22%, 15% or 12%, respectively. The effect of contamination by occult PCA alters the odds ratio and p-value of the results. CONCLUSION: It is important to recognize that contamination of the control population by occult carcinomas reduces the reliability of the results. Rigorous characterization of the experimental and control groups is needed in order to preserve the integrity of the conclusions.

Autopsy evaluation of a prostate cancer case treated with brachytherapy.

Morphological analyses of prostate specimens after brachytherapy are rare and present a challenge to the pathologist due to an inherent difficulty in determining the difference between dying glands and surviving cancer cells. We have taken the opportunity to analyze an autopsy specimen in an attempt to set criteria by which one can analyze post-radiation therapy prostate biopsies. The patient had undergone brachytherapy and experienced a clinical complete response based on undetectable prostate-specific antigen and died of unrelated disease. Immunohistochemical studies were performed with the following antibodies: p63, P504S/AMACR and high molecular weight cytokeratin (HMWCK). Using a combination of molecular staining techniques, we were able to conclude that there were no viable tumor cells present in the specimen. The requirement to use various techniques to come to this conclusion demonstrates inherent difficulty in differentiating viable tumor cells from those that may appear viable but have been affected by ionizing radiation and will be unable to undergo cell division. It is crucial that this uncertainty is kept in mind in making further management decisions in patients who have undergone radiation therapy and follow-up biopsy of the prostate gland.

Green light vaporization of the prostate: is it an adult technique?

INTRODUCTION: Intending to overcome transurethral resection of the prostate (TURP) in terms of safety maintaining its efficacy profile, have led to the introduction of minimally invasive laser therapies to treat men with lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO), each one with its unique properties. The aim of this review was to analyze and summarize all the existing data regarding the 180 W Xcelerated Performance System (XPS) photoselective vaporization of the prostate (PVP). EVIDENCE ACQUISITION: A systematic review was conducted: 45 papers were identified. After excluding those not in English language, duplicates, case reports and "expert opinion" papers, 39 articles were reviewed. EVIDENCE SYNTHESIS: The XPS emits a 532 nm wavelength generated using a lithium triborate crystal in a quasi-continuous mode through a 750 µm, continuously saline-cooled, metal capped MoXy™ fibre. This system has overcome the previous model in terms of surgical and functional outcomes. Although several techniques have been proposed, the IGLU modular one is considered the standard approach for 180 W PVP. Authors estimated the need for at least 120 cases to reach an expert level of competence. The GOLIATH Study has proven the non-inferiority of XPS PVP to TURP. The procedure is safe and effective also in large glands but long operative times still represent an issue. Considering the total average costs, XPS PVP provides and advantage over TURP. International guidelines consider PVP the best option to manage patients receiving anticoagulants or with a high cardiovascular risk. CONCLUSIONS: PVP should be considered an adult technique and, as suggested by the EAU Guidelines, is the best surgical option to manage patients receiving anticoagulant medication or with a high cardiovascular risk. The development of new surgical techniques such as APV, PEBE and seminal spearing approaches could represent a possibility to further implement the XPS indications. Dedicated unit could improve the management LUTS/BPO men.

Association of MnSOD AA Genotype with the Progression of Prostate Cancer.

PURPOSE: To investigate whether manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with the clinical significance of prostate cancer. MATERIALS AND METHODS: Prostates were obtained from 194 deceased men 45 years or older who did not have a history of prostate cancer. Serial sections and histological examinations of the prostate were performed. The MnSOD genotypes of the specimens were determined by polymerase chain reaction restriction fragment length polymorphism analysis. RESULTS: Of the 194 men, 31 and 26 had clinically insignificant and significant prostate cancer. Clinically significant cancer comprised 29% and 58% of the cancers in men <70 and >70 years old, respectively. The age-specific proportion of significant cancer significantly increased with the advance of age (p<0.001). MnSOD AA, as compared with the other genotypes (VA and VV together), was associated with significant prostate cancer across all ages, odds ratio (OR) 2.34, 95% confidence interval (CI) 0.99-5.49, and in men older than 69 years (OR 4.89, 95% CI 1.51-15.8), but not in men younger than 70 years. The genotype was not associated with clinically insignificant cancer regardless of age. The comparison between significant and insignificant cancer, the OR (95% CI) for MnSOD AA was 5.04 (1.05-24.2) (sensitivity 0.57, specificity 0.78, positive predictive value 0.78) in men older than 69 years. CONCLUSIONS: MnSOD polymorphism is strongly associated with the clinical significance of prostate cancer in men older than 69 years, but not in men younger than 70 years suggesting that oxidative stress may be involved in the progression of the disease. MnSOD may be a clinically useful marker to predict the potential of progression of prostate cancer.

Hybrid oncocytic/chromophobe renal cell tumours do not display genomic features of chromophobe renal cell carcinomas.

Hybrid oncocytic/chromophobe tumours (HOCT) are renal tumours recently described displaying histological features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (ChRCC), raising the question of their precise signification in the RO/ChRCC group. This study aimed to describe clinicopathological features of so called HOCT and to characterise their genomic profile. Five hundred and eighty-three tumours belonging to the ChRCC/RO group were retrospectively reviewed. Twelve tumours that could not be classified as RO or CHRC were considered as HOCT. Hale staining and cytokeratin 7 (CK7) immunostaining were performed. Genomic profile was established by array comparative genomic hybridisation (array-CGH) on frozen samples. Mean age at diagnosis was 70 years (range 46-83). No recurrence was observed (median follow-up: 18 months; range 9-72). Tumour size ranged from 1 to 11 cm. HOCT showed an admixture of RO- and ChRCC-like areas and/or "hybrid" cells with overlapping cytonuclear and/or histochemical features. Hale staining was apical in 50 to 100 % of cells, and CK7 was expressed in 10 to 100 % of cells. Genomic profile was balanced in seven cases or showed a limited number of random imbalances in five cases, as observed in RO. In no instances were observed the characteristic chromosome losses of ChRCC. These results suggest that so called HOCT are not true hybrid tumours and rather could represent a morphological variant of RO. From a diagnostic perspective, an array-CGH analysis could be performed in ambiguous ChRCC/RO cases to formally exclude the diagnosis of ChRCC.

Early T cell signalling is reversibly altered in PD-1+ T lymphocytes infiltrating human tumors.

To improve cancer immunotherapy, a better understanding of the weak efficiency of tumor-infiltrating T lymphocytes (TIL) is necessary. We have analyzed the functional state of human TIL immediately after resection of three types of tumors (NSCLC, melanoma and RCC). Several signalling pathways (calcium, phosphorylation of ERK and Akt) and cytokine secretion are affected to different extents in TIL, and show a partial spontaneous recovery within a few hours in culture. The global result is an anergy that is quite distinct from clonal anergy induced in vitro, and closer to adaptive tolerance in mice. PD-1 (programmed death -1) is systematically expressed by TIL and may contribute to their anergy by its mere expression, and not only when it interacts with its ligands PD-L1 or PD-L2, which are not expressed by every tumor. Indeed, the TCR-induced calcium and ERK responses were reduced in peripheral blood T cells transfected with PD-1. Inhibition by sodium stibogluconate of the SHP-1 and SHP-2 phosphatases that associate with several inhibitory receptors including PD-1, relieves part of the anergy apparent in TIL or in PD-1-transfected T cells. This work highlights some of the molecular modifications contributing to functional defects of human TIL.

Saturation biopsies for prostate cancer: current uses and future prospects.

Since its introduction, ultrasound-guided prostate biopsy has undergone significant evolution. Because of the low sensitivity of ultrasonography in detecting prostate cancer, tissue is sampled randomly within the gland. In an attempt to enhance cancer detection and characterization, the trend has been to increase the number of biopsy cores taken. Saturation biopsies of the prostate gland were first evaluated as a diagnostic tool. When performed as an initial procedure, saturation biopsies do not seem to improve cancer detection when compared to standard biopsy. However, saturation biopsies might be of clinical value in patients with previous negative standard biopsies but persistently rising PSA levels. As a staging tool, the use of saturation biopsies was proposed mainly to avoid overtreatment of clinically insignificant cancers. Results from clinical and autopsy studies have suggested that saturation biopsies are more accurate than standard biopsies in histological characterization of prostate cancer. Improving cancer characterization might require an increase in the number of cores taken, but knowing their precise location is paramount. Strict template guidance and three-dimensional techniques offer a more comprehensive approach than current ultrasound-guided approaches, and the advantage of precisely recording every core location. New imaging techniques, such as diffusion-weighted and spectroscopic MRI might also help in targeting prostate biopsies.

Association of prostate cancer and manganese superoxide dismutase AA genotype influenced by presence of occult cancer in control group.

OBJECTIVES: To investigate whether the inclusion of occult cancer in the control group can influence the association of prostate cancer and the polymorphism of manganese superoxide dismutase (MnSOD). METHODS: Prostate specimens and sera were obtained from 194 deceased men who did not have a history of prostate cancer. Eighteen-core biopsy specimens and whole-mount sections were evaluated histologically. The MnSOD genotype of the specimens was determined by polymerase chain reaction restriction fragment length polymorphism analysis. RESULTS: Tumors were present in 57 of the prostates, and biopsy detected 33 (including 1 false-positive finding). It detected 17 (1 false-positive finding) and missed 14 tumors in the subgroup of 135 specimens with a prostatic-specific antigen <4 ng/mL. The MnSOD AA genotype was associated with prostate cancer found in the step-sectioned specimens vs the control group in whom the absence of occult prostate cancer had been verified. However, no association was found if the control group consisted of subjects with negative biopsy results from the overall group or the subgroup with a prostatic-specific antigen level of <4 ng/mL. CONCLUSIONS: The MnSOD AA genotype was associated with prostate cancer in our study; however, contamination of occult prostate cancer in the control group reduced the power of analysis and might yield seemingly negative results. Epidemiologic studies should strive to include control groups with a verified absence of occult cancer.

The role of prevalence in the diagnosis of prostate cancer.

BACKGROUND: The worldwide incidence of prostate cancer has been rising rapidly, likely due to intensified effort in early detection and screening. Intense effort is also directed at novel schemas of chemoprevention and therapy. Incidence data are insufficient to identify the true magnitude of prostate cancer in a given population. The true prevalence of prostate cancer must be identified. METHODS: We reviewed the latest worldwide epidemiologic data and clinical studies on prostate cancer studying the true prevalence of this disease. RESULTS: The incidence of prostate cancer is increasing worldwide, with strong variation among regions. Prevalence studies based on autopsy data have confirmed a high frequency of latent prostate cancer in men of all ages. More aggressive screening measures using a lower prostate-specific antigen (PSA) threshold, together with an increasing number of biopsies, have escalated the detection of these latent cancers. CONCLUSIONS: Recent improvements in prostate cancer detection narrow the gap between the incidence and true prevalence of prostate cancer. This, however, raises concerns about the risk of over detection of latent cancers and thus identifying a need for improvement in screening strategies to better identify clinically significant disease.