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The Gleason score is the most important prognostic marker for prostate cancer patients, but it suffers from significant observer variability. Artificial intelligence (AI) systems based on deep learning can achieve pathologist-level performance at Gleason grading. However, the performance of such systems can degrade in the presence of artifacts, foreign tissue, or other anomalies. Pathologists integrating their expertise with feedback from an AI system could result in a synergy that outperforms both the individual pathologist and the system. Despite the hype around AI assistance, existing literature on this topic within the pathology domain is limited. We investigated the value of AI assistance for grading prostate biopsies. A panel of 14 observers graded 160 biopsies with and without AI assistance. Using AI, the agreement of the panel with an expert reference standard increased significantly (quadratically weighted Cohen's kappa, 0.799 vs. 0.872; p = 0.019). On an external validation set of 87 cases, the panel showed a significant increase in agreement with a panel of international experts in prostate pathology (quadratically weighted Cohen's kappa, 0.733 vs. 0.786; p = 0.003). In both experiments, on a group-level, AI-assisted pathologists outperformed the unassisted pathologists and the standalone AI system. Our results show the potential of AI systems for Gleason grading, but more importantly, show the benefits of pathologist-AI synergy.

Background: There are no comparative data on pathological predictors at diagnosis, between African Caribbean and Caucasian men with prostate cancer (PCa), in equal-access centers. The objective of this study was to evaluate the grade groups of an African Caribbean cohort, newly diagnosed with PCa on prostate biopsy, compared with a Caucasian French Metropolitan cohort., Methods: A retrospective, a comparative study was conducted between 2008 and 2016 between the University Hospital of Martinique in the French Caribbean West Indies, and the Saint Joseph Hospital in Paris. Clinical, biological, and pathological data were collected at diagnosis. The primary outcome was the grade groups for Gleason score; the secondary outcome was the PCa detection rate. Multivariate analysis was performed using linear regression., Results: Of the 1880 consecutive prostate biopsy performed in the African Caribbean cohort, 945 had a diagnosis of PCa (50.3%) and 500 of 945 in the French cohort (33.8%). African Caribbean patients were older (mean 68.5 vs 67.5 years; P = .028), had worse clinical stage (13.2% vs 5.2% cT3-4; P < .001) and higher median prostate-specific antigen (PSA) level (9.23 vs 8.32 ng/mL; P = .019). On univariate analysis, African Caribbean patients had worse pathological grade groups than French patients (P < .001). Nevertheless, after adjustment on age, stage, and PSA, there were no significant differences between the two cohorts (P = .903)., Conclusion: African Caribbean patients presented higher PCa detection rate, and higher grade groups at diagnosis than French patients in equal-access centers on univariate analysis but not on multivariate analysis. African Caribbean patients with equivalent clinical and biological characteristics than Caucasian patients at diagnosis might expect the same prognosis for PCa., (© 2019 Wiley Periodicals, Inc.)

Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high. Improvements to patient selection and identification of at-risk patients are central to reducing mortality. We aimed to determine if cancer aggressiveness correlates with androgen levels in patients undergoing radical prostatectomy for localized PCa. We performed a prospective, multicenter cohort study between June 2013 and June 2016, involving men with localized PCa scheduled to undergo radical prostatectomy. Clinical and hormonal patient data (testosterone deficiency, defined by total testosterone (TT) levels < 300 ng/dL and/or bioavailable testosterone (BT) levels < 80 ng/dL) were prospectively collected, along with pathological assessment of preoperative biopsy and subsequent radical prostatectomy specimens, using predominant Gleason pattern (prdGP) 3/4 grading. Of 1343 patients analyzed, 912 (68%) had prdGP3 PCa and 431 (32%) had high-grade (prdGP4, i.e., ISUP ≥ 3) disease on prostatectomy specimens. Only moderate concordance in prdGP scores between prostate biopsies and prostatectomy specimens was found. Compared with patients with prdGP3 tumors (i.e., ISUP ≤ 2), significantly more patients with prdGP4 cancers had demonstrable hypogonadism, characterized either by BT levels (17.4% vs. 10.7%, p < 0.001) or TT levels (14.2% vs. 9.7%, p = 0.020). BT levels were also lower in patients with prdGP4 tumors compared to those with prdGP3 disease. Testosterone deficiency (defined by TT and/or BT levels) was independently associated with higher PCa aggressiveness. BT is a predictive factor for prdGP4 disease, and evaluating both TT and BT to define hypogonadism is valuable in preoperative assessment of PCa (AndroCan Trial: NCT02235142).

Introduction: The influence of the delay between prostate biopsy and radical prostatectomy for patients with localized prostate cancer is controversial. The objective of this study was to establish a time limit between prostate biopsy and radical prostatectomy beyond which the risks of upgradging and biochemical recurrence (BCR) are increased., Material and Methods: Between January 2013 and January 2017, a retrospective analysis of the clinical, biological and histological data of 513 patients treated with radical prostatectomy for localized prostate cancer was performed in a single center. The primary endpoint was the assessment of the risk of BCR by the difference between post-biopsy USCF-CAPRA and post-surgical CAPRA-S scores. The secondary endpoint was the evaluation of the upgrading by the difference between the Gleason score on biopsy and on surgical specimen. The risks of BCR and upgrading were compared by Student test according to different delays between prostate biopsy and radical prostatectomy. The shortest delays for which a significant difference was found were reported., Results: In this study, 513 patients were included. The median age at the time of the biopsy was 65 years (IQR: 60-69). The median preoperative PSA was 7.30ng/mL (IQR: 5.60-9.94). The median time between biopsy and surgery was 108 days (IQR: 86-141). For the entire cohort, the risk of BCR was significantly higher above a threshold of 90 days (P=0.039). No threshold was found for Gleason 6(3+3) patients. A 90-day threshold was found for Gleason 7(3+4) patients (P=0.038). Gleason patients≥8 had more upgrading beyond a 60-day threshold (P=0.040)., Conclusion: Our study showed that after a 3 months delay, the risk of BCR was significantly higher for localized prostate cancer. It seemed possible to extend this period for low-risk patients, whereas it seemed necessary to keep it for intermediate-risks and to reduce it to 2 months for high-risks., Level of Evidence: 4., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: We aim to correlate multiparametric magnetic resonance imaging (mpMRI) of the prostate reporting (Prostate Imaging Reporting and Data System [PI-RADS] version 2) with the Gleason score into both radical prostatectomy (RP) specimen and MRI fusion-targeted biopsies (FTB)., Methods: mpMRI of 74 patients who underwent an RP after FTB were retrospectively reviewed. The Gleason score distribution was compared according to the PI-RADS score using the Kruskal-Wallis test. Results were compared to those of the mpMRI-guided biopsy of the same anatomical zone. For comparison, 903 RP specimen and their corresponding classical biopsies were also reviewed. Cohen's kappa concordance test was used to compare biopsies and prostatectomy specimen analyses., Results: An exact match between Gleason grade in RP specimen and FTB was found in 62% of the cases. There was no significant difference in Gleason score ≤7 (3 + 4) vs. ≥7 (4 + 3) distribution according to the PI-RADS scores (p = 0.096). Overall, Kappa coefficients were similar with MRI-targeted biopsies compared to classical biopsies (κ = 0.378, 95% CI [0.194-0.563], and κ = 0.316, 95% CI [0.259-0.374], respectively)., Conclusions: PI-RADS score was not associated with significant differences regarding Gleason score distribution within target. Moreover, concordance of Gleason score in both MRI-targeted and classical biopsies with those within target in RP specimen was weak., (© 2017 S. Karger AG, Basel.)

To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer, we searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects. The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system. A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review. We attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we do not recommend its use in mass screening. Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA (n=5); fusion oncogenes (n=2). These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality. The LoE attributed was III-C. PSA can be used for early prostate cancer detection but mass screening is not recommended. Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed. A better use of available tests is possible for men at risk in order to maximize the risk-benefit ratio.

Background: To compare histological feature of prostate cancer (PCa) according androgenic status in patients who underwent radical prostatectomy (RP)., Methods: Between March 2007 and September 2013, we prospectively analysed 937 patients who were referred to our centre for RP. Clinical, pathological and biological data have been prospectively collected. Preoperative total testosterone (TT) and bioavailable testosterone (BT) serum determinations were carried out. The threshold for low serum testosterone was set at TT<3 ng/ml. Preoperative PSA value was registered. Gleason score (GS) and predominant Gleason pattern were determined in prostate biopsies and in prostate tissue specimens, crosschecked by two uro-pathologists., Results: Nine hundred and thirty-seven consecutive patients were included. In all, 14.9% patients had low TT in the population. An exact match between biopsy and prostate specimens in GS grading was observed for 50.6% patients (n=474). Also, 40.9% of all patients were upgraded (n=383): 45.3% (n=63) in low serum testosterone patients and 40.1% (n=320) in normal serum testosterone patients. For prostate specimens, the proportion of patients with predominant Gleason pattern 4 was higher in patients with low TT compared with normal TT (41.7% vs 29.1%, P=0.0029). In all, 20.1% were upgraded from predominant Gleason pattern 3 on biopsies specimen to predominant Gleason 4 pattern on the prostate specimen in patients with low TT, whereas 11.6% were upgraded for normal TT patients (P=0.002)., Conclusions: Low serum testosterone is an independent risk factor for predominant Gleason pattern 4 on prostate specimen after RP and for upgrading from low- to high-grade cancer between prostate needle biopsies and RP specimen. This observation should be taken into account in localised PCa management, especially for active surveillance or when a nerve-sparing approach is considered.

Purpose: Positive surgical margins (PSMs) after radical prostatectomy (RP) are a known factor associated with biochemical recurrence (BCR) and raise the issue of adjuvant treatment by radiotherapy versus salvage treatment at recurrence. To help this choice, our study aimed to analyze BCR-free survival and factors associated with BCR in patients with PSM and undetectable postoperative prostate-specific antigen (PSA)., Methods: Between 2005 and 2008, 630 patients had RP for localized prostate cancer in our center. We included patients with PSM, uninvaded nods, undetectable postoperative PSA and no adjuvant treatment. The 5-year BCR-free survival was calculated using Kaplan-Meier method. Logistic regression models were used to determine the factors associated with BCR in univariate and multivariate analyses (Cox model)., Results: The PSM rate was 32.7 % (n = 206 patients), and 110 patients corresponded to the inclusion criteria. The median follow-up was 72 months. The BCR rate was 30 % with a 5-year BCR-free survival of 83.9 %. The factors significantly associated with BCR were preoperative PSA, predominance and percentage of Gleason 4, tumor volume, PSM length and predominance of Gleason 4 at the margin. In the multivariate analysis, the remaining two significant factors were PSM length [OR 4.35, 95 % CI (1.011-1.421), p = 0.037] and tumor volume [OR 4.29, 95 % CI (1.011-1.483), p = 0.038]., Conclusion: Over a 5-year follow-up, only one-third of patients experienced BCR. It might be reasonable to postpone adjuvant radiotherapy for patients with PSM and undetectable PSA after RP. Tumor volume and PSM length were associated with BCR and should be taken into account in the postoperative treatment management.

Objectives: Handling and pathologic analysis of radical prostatectomy specimens are crucial to confirm the diagnosis of prostate cancer and evaluate prognostic criteria., Material and Methods: A systematic review of the scientific literature was performed in the Medline database (PubMed), using different associations of the following keywords: prostate cancer; prostatectomy; specimen; handling; pathology; tumor staging; Gleason score; surgical margin; prognosis; frozen section; lymph node; biomarkers. A particular search was done on specimen management and characterization of tissue prognostic factors., Results: Handling of both radical prostatectomy specimen and lymph node dissection is standardized according to international criteria. Although the main histoprognostic factors are still Gleason score, pathologic staging and margin status, these criteria have been refined these last 10 years, allowing to improve the prediction of relapse after surgical treatment., Conclusion: The standardization of handling and pathology reporting of radical prostatectomy specimens will be mandatory for treatment uniformization according to risk stratification in prostate cancer and personalization of therapeutic approaches., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Introduction: The sub Comittee prostate of the CCAFU established guidelines for diagnostic, treatment, evaluation and standart of care of prostate cancer., Methods: Guidelines 2010 were updated based on systematic literature search performed by the sub-Comittee in Medline and PubMed databases to evaluate references, levels of evidence and grade of recommandation., Results: Pathological examination of the tissue specimens was defined specifically for Gleason score according to ISP 2005 recommandations. Prostate and pelvis RMN became the reference in terms of radiological exam. Individual and early diagnosis of prostate cancer was defined and role of PSA was precised. Active surveillance became one of the standart of care of low-risk tumors, radical prostatectomy remained one of the options for all risk group tumors, length of hormonotherapy in association with radiotherapy was precised according to the risk group. Side effects of hormonotherapy treament needed specific supervision ; hormonotherapy had no indication in case of non metastatic tumors and intermittent hormonotherapy in metastatic tumors. New hormonal drugs in pre and post chemotherapy and bone target drugs opened new therapeutics pathways., Conclusion: From 2010 to 2013, standarts of care of prostate cancer were modified because of results of prospective studies and new therapeutics. They allowed precise treatments for each specific clinical situation. In the future, multidisciplinary treatments for high risk tumors, time of adjuvant treatment and sequencies of new hormonal treatment had to be defined., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

In 2009, prostate cancer was the subject of a large number of communications in international urologic, oncologic and radiation therapy conferences. The most interesting studies that are likely to modify physician's daily practice were selected. This year the results from the European (ERSPC) and the American (PLCO) mass screening studies. Many abstract on prevention, natural history and tumor markers such as PCa3 and fusion gene TMPRSS2 : ERG were presented. Adjuvant hormonal treatment was evaluated in high-risk patients. Hormonal and radiation therapy association reduces recurrence, specific and overall mortality in locally advanced prostate cancer. Intermittent hormonal treatment is an option in hormone sensitive metastatic patients. toremifene and denosumab were evaluated in the prevention of fracture risk in patients under androgen deprivation therapy. The mechanism of tumor proliferation in castrate resistant prostate cancer further explained and 2 new molecules abiraterone and MDV 3100 were presented.

The identification of fusion genes provides new insights into the initial mechanisms of molecular events implicated in the prostate cancer tumorigenesis. The presence of TEMPRSS2-ETS fusion in up to half of all human prostate cancer makes it perhaps the most common genetic rearrangement in human epithelial tumors. Some data suggest that TMPRSS2-ERG fusion prostate cancers have a more aggressive phenotype, which may affect cancer progression and outcome in localized tumors treated with prostatectomy. This discovery should pave the way towards future targeted therapies.

Only few studies have been published regarding the results of radical Prostatectomy (RP) in elderly patients. The available data suggest that advanced age does not increase the postoperative mortality and morbidity rates, as far as reasonable selection is performed. Similarly, oncological results of RP are similar in patients aged >70 years and in younger patients. Only the risk of incontinence may be increased, with a potential impact on quality of life. There are no studies comparing the various curative treatments of Prostate cancer (RP, radiation therapy, brachytherapy, active surveillance) in the elderly population., ((c) 2009 Elsevier Masson SAS. All rights reserved.)

Prostate cancer (PaC) is a significant health problem. Elderly have the highest incidence of the disease as age is its strongest risk factor. Despite its complications, the use of androgen suppression in aging patients with prostate cancer has become extremely frequent with probable excess. However, some of these complications carry specific mortality and all of them have a negative impact on quality of life. It is critical to perform a geriatric assessment, concerning physical, mental and social items, before to consider androgen suppression in this population. Indications of androgen suppression for the treatment of prostate cancer follow the guidelines of CCAFU. Delayed treatment deserves a special attention when possible. Treatment modalities are no specific to the elderly, but complications have to be anticipated with preventive measures. Intermittent androgen suppression should be considered with caution. Close follow up will focus on the diagnosis of adverse effects of androgen suppression., ((c) 2009 Elsevier Masson SAS. All rights reserved.)

The aging of the population has resulted in an increase in the number of elderly patients with prostate cancer. Among the curative treatment options in the elderly subject, external radiotherapy is the most frequently chosen option. Combined treatment including radiotherapy and hormone therapy should be preferred to hormonal therapy alone, including in elderly patients, whenever life expectancy surpasses 4-5 years. The indications for this radiotherapy should be defined in an attempt to prevent excessive or insufficient treatment, to adapt the treatment modalities to the patient's age by assessing its potential toxicity, and to discuss the possible alternatives. In cases of localized prostate cancer in men who are aging well, a standard treatment should be proposed, preferring radiotherapy possibly associated with hormone therapy in cases with negative prognostic factors. Patients with a reversible health problems can also receive standard treatment, notably in cases with aggressive prognostic factors., ((c) 2009 Elsevier Masson SAS. All rights reserved.)

Total prostatectomy remains the main treatment for intermediate risk prostate cancer with a life expectancy greater than 10 years. In other cases non-surgical treatments can be proposed: external radiotherapy (exclusive or combined anti-androgen therapy), brachytherapy with permanent implants, high frequency ultrasounds (HIFU, Ablatherm), cryotherapy or exclusive hormonal treatment. For such patients in case of biological recurrence, prostate biopsies are usually performed in order to affirm the local recurrence. The histological confirmation of persistent tumor is usually required before any treatment: salvage surgery, cryotherapy, and brachytherapy or high intensity focused ultrasound (HIFU). Pathologists must be aware of the histological modifications induced by these different treatments in order to ensure an optimal interpretation of the biopsies. In this review, we describe the modifications observed in the normal prostate and in cancers after these various therapeutic methods, and also after alpha reductase inhibitors proposed as treatment of benign prostate hypertrophy and prostate cancer chemoprevention.

The histological grading system of prostate cancer proposed by David Gleason in 1966 remains, more than 40 years after its princeps use, an essential tool of communication between the pathologists and urologists. We present here the principal modifications of this score proposed in 2005 by the International Society of Uropathology.

Prostate cancer with 60,000 new cases a year is a public health problem which requires adapted and effective responses. The era of PSA screening dramatically increased the number of prostate biopsies that pathologists have to screen and consequently the number of difficult cases requiring analysis. Immunohistochemistry with anti-AMACR/p504s is useful for detecting prostate cancer in the full range of prostate specimens encountered in needle biopsies. In particular, studies to date with AMACR/p504s clearly demonstrate the ability of this marker to support a diagnosis of malignancy in prostate needle biopsies, combined with negative staining for a basal cell marker, such as p63. This study conducted by the Prostate Committee of the French Association of quality assurance in pathological anatomy and cytology (AFAQAP), reports the evaluation of the current practices with available anti-p63 and -p504s antibodies. The results of this investigation show a correct evaluation of the immunostaining procedure. Overall, from the 39/56 structures tested, the value of the test was positive in 85%. The best results were obtained after antigenic restoration with TRIS-EDTA pH 9, p504s (13H4, 1/200) and p63 (A4A, 1/100).

The identification of fusion genes provides new insights into the initial mechanisms of molecular events implicated in the tumorigenesis of prostate cancer. The presence of TEMPRSS2-ETS fusion in up to half of all human prostate cancers makes it perhaps the most common genetic rearrangement in human epithelial tumors. Some data suggest that TMPRSS2-ERG fusion prostate cancers have a more aggressive phenotype which may affect cancer progression and outcome in localized tumors treated with prostatectomy. This discovery should pave the way towards future targeted therapies.

Prostate biopsies remain the only way to confirm the presence of prostate cancer. Nevertheless, the ideal number of biopsies needed to establish the diagnosis is prone to controversy. The current European guidelines recommend 12 sextant biopsies. Few recommendations concerning how the biopsies should be handled have been published. In France, in order to avoid the loss of histological specimens, it was strongly recommended to transmit each core biopsy to the pathology department in an independent container. Performing a large number of biopsies means an increase in the number of containers transmitted and consequently a technical overload of the transmission network, which occurs without any financial counterpart. Since the current tarification system establishes cost allotment by activity, there is no room for an increased technical workload schedule. New approaches must be developed in order to increase productivity. The main aim of our study was to search for answers to the question whether it would be possible to use only one container per sextant irrespective of the number of biopsies performed. For this purpose, we performed various series of one, two, three, four or six biopsies from fresh total prostatectomies with an automatic prostate biopsy gun. All the biopsies were paraffin embedded after a 4% formalin fixative procedure. All the cores were measured after fixing, and on HES slides. The 48 series were as follow: 10 cases with one core, 16 cases with two cores, 13 cases with three cores, five cases with four cores and three cases with six cores. The average length of each core before inclusion varied from 11,8mm to 16,3mm. The average length on HES slides from 9,7 to 11,5mm. A significant difference was observed only for the blocks containing six biopsies (p=0.02). Inclusion of one to three cores from each sextant, did not lead to a loss of information or loss of chances for the patient.

The PCPT (Prostate Cancer Prevention Trial) trial which compared 5 mg/d of finastéride to placebo in men over 55 years old showed that active treatment reduced the incidence of prostate cancer from 24.4 to 18.4%. Paradoxically, the incidence of high grade cancers (Gleason score > or = 7) was higher in the finasteride group (6.4%) than in the placebo group (5.1%). Histological interpretation of the radical prostatectomy specimens showed an overestimation of Gleason score on biopsy both in the finasteride and placebo group. The high grade cancers on total prostatectomy specimens were not more aggressive in the finasteride arm than in the placebo arm. There is no argument to suggest that long term finasteride may promote the development of highly aggressive cancer. Urologists must clearly be aware that finasteride treatment may result in morphological changes in order to inform the pathologist that this drug is being taken. If a prostate cancer with a Gleason score > or = 7 is diagnosed in a treated patient, the pathologist will perform a double reading of the slides to confirm the score.

Before radical prostatectomy, the pathologist analyzes the prostate biopsies. He has to affirm the diagnosis of cancer when present, and to provide prognosis parameters such as the Gleason score, the percentage of tumor, and to report an extraprostatic extension when present. After the radical prostatectomy, the pathologist has to analyze the surgical specimen. Two main features have to be reported including the tumor stage and the Gleason score.

The use of serum prostate-specific antigen screening to facilitate early detection of prostate cancer has resulted in a dramatic increase in the number of prostate needle core biopsies which pathologists must examine. This has been accompanied by a strong increase in the number of biopsies with ambiguous lesions, and an unequivocal diagnosis of malignancy is difficult to render, especially in the case of limited foci or in small atypical acinar lesions. When assessing small foci of atypical glands upon needle biopsy, the pathologist searches for differences between the benign glands and atypical glands in terms of usual morphological features and in such cases, immunohistochemical stains for basal cell markers such as 34betaE12 antibody or antibodies directed against cytokeratin 5 and 6 and more recently p63 may be a useful adjuvant to identify basal cells which are typically present in benign glands but absent in prostatic carcinoma. However several benign mimickers of prostate carcinoma, including atrophy, atypical adenomatous hyperplasia, nephrogenic adenoma can stain negatively with these antibodies and thus a negative basal cell marker immunostain alone does not exclude a diagnosis of benignancy. Alpha-methyl-coenzyme-A-racemase (AMACR) a new sensitive marker of prostate carcinoma, can be useful in confirming ambiguous lesion suspected for malignancy. Although, as with any immunohistochemical studies, problems exist in terms of both sensitivity and specificity. The aim of this review is to describe the histological features of prostatic carcinoma in case of small focus, and discuss the application of these new prostatic markers in the light of the current literature to highlight the best practice guidelines.

The examination by the pathologist of the whole prostate gland after radical prostatectomy allows close inspection of the tissue in order to determine the presence or absence of important prognostic pathological parameters, such as the histological grade, extracapsular extension, seminal vesicle invasion, positive surgical margins. Only complete embedding and multiple close steps sectioning of the whole prostate gland allows the more accurate assessment of the margin status. Specimens not sectioned from the whole organ carry the likelihood of missing important adverse pathologic features. The vast majority of departments of pathology in French institutions are used to study radical prostatectomy specimens obtained from the entire prostate gland.

Objective: To investigate the potential utility of a new combined immunostaining technique for diagnosing prostate cancer from histological analysis of needle biopsy specimens., Materials and Methods: Tissue was immunostained with a combination of antibodies against a basal cell marker (p63), and an enzyme commonly overexpressed in prostate cancer (p504s), on 63 small prostate cancer foci (<1 mm) and 109 cases of ambiguous lesions observed in needle biopsies., Results: After p63/p504s immunostaining, 93% of the ambiguous lesions (102/109) were classified. The final diagnoses retained were: 92 prostate cancers, seven atypical small acinar proliferations suspected of being malignant but undiagnosed, 21 prostatic intraepithelial neoplasia, five atypical adenomatous hyperplasia, and 36 atrophic benign mimickers of cancer., Conclusions: Combining p504s as a positive marker for prostate cancer and p63 as a negative marker might improve diagnostic performance, sensitivity and specificity, and lead to fewer false-negative results. This simple immunostaining procedure should reduce the percentage of residual ambiguous lesions and the need for additional biopsies.

Objectives: To examine the morphologic alterations of finasteride therapy on prostate cancer compared with no treatment or treatment with a luteinizing hormone-releasing hormone (LHRH) agonist and the clinical outcomes of patients treated with finasteride., Methods: The data of 56 patients with prostate cancer who had taken finasteride for at least 6 months were reviewed. A central pathology review was performed in a blinded manner comparing these patients with 56 matched controls and 44 patients who received a 3-month course of LHRH agonist before radical prostatectomy. The histologic hormonal treatment effects included apoptosis, vacuolated cytoplasm, pyknotic nuclei, and small irregular glands. An overall consensus was scored using a three-tiered system: no apparent effect (score = 0), suspicious for hormonal effect (score = 1), and highly suggestive of hormonal treatment (score = 2). A Gleason score was assigned to all prostatectomy specimens., Results: The mean hormonal treatment score for the prostatectomy specimens was 0.4, 0.5, and 1.6 for the control, finasteride, and 3-month LHRH groups, respectively. Surprisingly, 20% of control patients had suspicious or highly suggestive hormonal effects and 26% of the finasteride-treated patients did so. For the LHRH-treated group, only 23% did not demonstrate classic features of hormonal treatment. Similar clinical outcomes were observed between the finasteride and control groups., Conclusions: No consistent hormonal therapy effects with finasteride treatment were observed compared with LHRH agonists. The hormonal effect was observed in the control group. Therefore, although other aspects of the Prostate Cancer Prevention Trial design might account for the greater percentage of Gleason grade tumors in the study arm, morphologic changes due to long-term finasteride treatment were not a likely cause.

The diagnosis of prostate cancer is based on histological examination of prostatic biopsies using histological criteria identified on standard stains. In certain lesions mimicking prostate cancer, the pathologist must perform immunohistochemical studies looking for loss of basal cells and antibodies directed against cytokeratin CK 903 (34bE12) or CK5/6, which sometimes give inconclusive results leading to a diagnosis of suspicious site. The discovery of overexpression of alpha-méthylacyl CoA racemase in prostate cancer using a microarray technique has allowed the development and marketing of an antibody (P504S /AMACR) which, in combination with a new basal cell marker (p63), is a very valuable tool for the pathologist in the management of suspicious sites and cancers less than 1 mm in diameter detected on prostatic biopsies.

The treatment of prostate cancer by endocrine therapy induces histological changes of benign or malignant prostate glands. Treated cancers often have a more suspicious architecture, resulting in a higher Gleason score, while their nuclear grade (WHO) appears to be more reliable due to a reduction of the size of nuclei. Most authors appear to agree that cancers discovered by biopsy in patients treated with endocrine therapy should not be graded. A review of the literature appears to indicate that finasteride has less marked histomorphological consequences than other hormone-suppressor treatments and could have a lesser effect on the Gleason score. This paper, based on a review of the literature on this subject, emphasizes: (1) the extent of histological changes after androgen deprivation endocrine therapy; (2) histological changes after Finasteride and the difficulties of histological interpretation, particularly the risk of overestimating the Gleason histoprognostic score; (3) the need for urologists to indicate any treatment by 5-alpha-reductase inhibitors or androgen deprivation when requesting histological examination; (4) the value of collecting and documenting cases observed in the Uropathology Club in collaboration with the Oncology committee of the Association Française d'Urologie.

Prostatic needle biopsy is the preferred method for diagnosing early prostate cancer, providing specific information. In cases of histological cancer mimics, a diagnosis of atypical small acinar proliferation suspected of but not diagnosed as malignancy can be made. In such cases, and in small focus carcinomas, pathologists use 34betaE12, cytokeratin (CK) 5/6 or p63 immunostaining to label basal cells, and alpha-methylacyl-CoA racemase (AMACR/p504s) immunostaining as a positive prostate cancer marker on two distinct slides. However, in cases of small foci, ambiguous lesions might disappear. The purpose of our study was to improve the sensitivity of a cocktail of two antibodies (p63/p504s) with a sample incubation on 260 prostatic specimens, in order to help make a decision in conjunction with standard histology and CK 5/6 immunostaining. We tested 101 small focus prostatic cancers, 104 atypical small acinar proliferation, 19 high-grade prostatic intraepithelial neoplasia, two atypical adenomatous hyperplasia and 34 benign mimics of cancer. After p63/p504s immunostaining, the final diagnoses retained were as follows: 154 prostatic cancers, 14 atypical small acinar proliferation, 30 high-grade prostatic intraepithelial neoplasia, three atypical adenomatous hyperplasia and 62 benign mimics of cancer. To differentiate malignant from benign lesions, we used the criteria of greater sensitivity to p504s/p63 (95%) than to CK 5/6 (57%) or p63 (86%), and higher specificity for p504s/p63 (95%) than for CK 5/6 (88%) or p63 (81%). With the p504s/p63 cocktail, 89% of the ambiguous lesions were classified vs 53% for CK 5/6. Combined use of the two antibodies, one (p504s) as a positive marker and the other (p63) as a negative marker, with a simple immunostaining procedure, may improve diagnostic performance, sensitivity and specificity, leading to a reduction in the risk of false negatives; this technique in cases of atypical small acinar proliferation should reduce the percentage of residual ambiguous lesions and the need for additional biopsies.

Introduction: Pelvic lymphadenectomy for localized prostate cancer (stage T1-T2) provides prognostic information. It can be performed by laparoscopy or by open surgery. Systematic lymphadenectomy is controversial and should be performed according to the stage of the tumour and the type of management. Frozen section examination of lymph nodes during total prostatectomy is also controversial due to its low sensitivity (66%). The objective of this article is to define the indications for lymphadenectomy and frozen section examination., Methods: Systematic review of the literature., Results: Recommendations concerning the indications for bilateral pelvic lymphadenectomy and frozen section examination for stage T1-T2 prostate cancer as a function of the risk of lymph node metastases. A low risk (<5%) of lymph node metastases is defined by an initial PSA < 10 ng/ml, a Gleason score of biopsies < 7 (3 + 4 or < 50% of grade 4) and possibly non-suspicious lymph node imaging. In this case, prior pelvic lymphadenectomy either some time before or immediately before local treatment is optional (Level of Evidence III-2). Due to the morbidity related to lymphadenectomy, the benefit of the procedure is not justified. However, the following situations are distinguished for open or laparoscopic total prostatectomy: --if open total prostatectomy is considered, exploration of the lymph nodes by palpation at the beginning of the operation is recommended. If exploration does not suggest any lymph node invasion, lymphadenectomy is then optional (without frozen section examination). If exploration shows induration or a mass deforming the shape of the lymph nodes, lymphadenectomy is recommended. Frozen section examination is requested only when the surgeon decides not to perform prostatectomy in the case of lymph node invasion. Lymphadenectomy without frozen section examination is optional in the case of laparoscopic total prostatectomy. Macroscopic examination of any lymph node invasion is less accurate via laparoscopy. A high risk (> 5%) of lymph node metastases is defined by a PSA > 10 ng/ml and/or a Gleason score > 7 (4 + 3 or > 50% of grade 4), and/or suspicious lymph node imaging. Pelvic lymphadenectomy is then recommended (Level of Evidence III-2). The following situations can be distinguished according to the type of treatment envisaged (total prostatectomy or external radiotherapy): when the surgeon decides not to perform total prostatectomy in the case of microscopic or macroscopic lymph node invasion (pN1), lymphadenectomy (open or laparoscopic) may be performed either before or at the same time as prostatectomy with frozen section examination. In the case of external radiotherapy, laparoscopic (or open) lymphadenectomy is recommended (without frozen section examination) when it is decided to extend the irradiation field to pelvic lymph nodes in the case of stage pN1 (1st option) or withhold radiotherapy (2nd option). Lymphadenectomy is optional in other cases, as lymphadenectomy induces considerable morbidity and the benefit of systematic pelvic lymph node irradiation has not been demonstrated. It should be stressed that all indications for lymphadenectomy for localized prostate cancer proposed in the literature are based on the results of standard or limited pelvic lymphadenectomy. These indications could be revised if it is confirmed that lymphadenectomy extended to the internal iliac nodes, for patients at high risk of lymph node invasion, is truly informative and contributive to the treatment decision.

Unlabelled: Numerous lesions of the prostate, such as atrophy, adenomatous atypical hyperplasia (adenosis) or PIN can be misdiagnosed with prostatic cancer, and confused with ASAP, leading to perform additional biopsies. In such lesions, the pathologist can perform an immunohistochemical study with the anti-high molecular weight cytokeratin antibody CK903 (34bE12), which confirms the absence of basal cells and supports the diagnosis of prostatic cancer., Aim of the Study: To compare markers of basal cells (cytokeratin 5/6, p63) and the marker of prostatic carcinomatous glands (p504s) or alpha methylacyl-CoA racemase (AMACR)., Material and Methods: Retrospective study of 44 cases of paraffin-embedded prostatic specimens (36 biopsies, 4 PER, 1 adenomectomy and 3 radical prostatectomies), consisting in 20 cases of prostatic carcinomas (2 intraductal, 12 Gleason 6 (3+3), 4 Gleason 7 (4+3), 2 Gleason 8 (4+4)), 11 ASAP, 9 PIN (2 low grade, 7 high grade (2 isolated)), and 10 benign lesions (8 atrophy, 1 atypical adenomatous hyperplasia and 1 case of clear cell cribriform hyperplasia). All cases were tested with antibodies to CK 5/6, and with a cocktail to p63 and p504s, after heat antigenic retrieval on NEXES Ventana processor., Results: Basal cells of normal prostatic glands stained with CK5/6 and p63 in 91,3% and 100% of cases, independently from the fixation procedure (Bouin or Formalin). Carcinomas had a p63-/p504s+ profile, PIN were p63+/p504s+, and benign lesions were p63+/p504s-. We observed an increase in sensitivity: p63/p504s (100%), CK5/6 (80%), p63 (90%), p504s (95%), and specificity: p53/p504s (90%), CK5/6 (87.5%), p63 (90.5%), p504s (90.9%)., Conclusion: Our results show that the use of a cocktail to p63/p504s is more specific than the use of CK5/6 alone this technique supports a diagnosis of prostatic cancer in 40% of cases previously considered as ASAP.

The Gleason system is the internationally recognized standard for grading prostate cancer, due mainly to its strong prognostic capability. However, interobserver reproducibility is variable in the community setting. Herein we present a novel approach to evaluating Gleason grading among pathologists using high-density tissue microarrays (TMAs). A CD-ROM containing 537 different TMA spot images of 0.6-mm diameter was sent to 10 genitourinary pathologists in France. The pathologists were expected to score each TMA spot based on their experience evaluating standard prostate biopsies, transurethral resections, and prostatectomy samples. There was no consensus meeting beforehand to agree on how the group would apply the Gleason grading system for this project. Percentage of agreement and kappa value were used to assess the level of agreement. A short questionnaire was sent to assess pathologists' opinion on this new approach to evaluating Gleason grading. An average of 311 images were analyzed (range, 104 to 537; median, 256.5). Four of the pathologists evaluated all 537 images and assigned Gleason grades to 149 images with an overall kappa for interobserver agreement for the exact score between 0.31 and 0.52 and between 0.45 to 0.69 if 3 Gleason categories (7) were used. When 2 categories were considered (7), kappa ranged from 0.58 to 0.83. All pathologists analyzed 104 images. Similar results were obtained with an agreement between 0.28 and 0.54 for the 3 Gleason categories. After finishing this test, 90% of genitourinary pathologists considered this approach useful for resident training and 90% for pathology teaching. We conclude that a Gleason score can be easily assigned to each TMA spot of a 0.6-mm-diameter prostate cancer sample. These data also indicated that using TMA spot images may be a good approach for teaching the Gleason grading system due to the small area of tissue.

Context: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical speciality societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery., Objectives: Produce clinical practice guidelines for the radiotherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project., Methods: The FNCLCC and the French Urology Association (AFU) designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers., Results: The main recommendations are: 1/ a minimal dose of 70 Gy must be used, whatever the prognostic factors; 2/ it appeared that patients with favourable prognostic indicators (stage T1-2, PSA < or = 10 micrograms/L and Gleason score < or = 6) do not benefit from a dose escalation effect for doses over 70-74 Gy; 3/ patients with intermediate prognosis are the ones who benefit most from the dose escalation effect over 74 Gy, provided they receive exclusive radiation therapy; 4/ whenever possible, patients should be included in controlled trials designed to assess the effects of dose escalation and hormonotherapy.

Context: The "Standards, Options and Recommendations" (SOR) collaborative project was initiated in 1993 by the Federation of the French Cancer Centres (FNCLCC), with the 20 French Regional Cancer Centres, several French public university and general hospitals, as well as private clinics and medical specialty societies. Its main objective is the development of serviceable clinical practice guidelines in order to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review, followed by a critical appraisal by a multidisciplinary group of experts. Draft guidelines are produced, then validated by specialists in cancer care delivery., Objectives: Produce clinical practice guidelines for the brachytherapy of prostate cancer using the methodology developed by the Standards, Options and Recommendations project., Methods: The FNCLCC and the French Urology Association (AFU) first designated the multidisciplinary group of experts. Available data were collected by a search of Medline and lists selected by experts in the group. A first draft of the guidelines was written, they validated by independent reviewers., Results: The main recommendations are: 1/Brachytherapy with permanent seeds alone is a possible curative treatment for prostate cancer patients with the following prognosis factors: tumour stage T1 or T2a (TNM 1992), Gleason score < or = 6 and PSA < 10 micrograms/L. 2/Combined treatment with brachytherapy and hormonal therapy could be more efficient than brachytherapy alone for prostate cancer patients with Gleason score > 7 and/or PSA > 10.3/Combination of brachytherapy and external beam radiation therapy can be proposed to prostate cancer patients with intermediate prognosis. 4/Before and after seed implantation, risks of infection must be prevented by appropriate antibiotic therapy (recommendation). 5/Brachytherapy must not be performed within 2 months of transurethral prostate resection. 6/The height of the urethra receiving more than 200% of the prescribed dose must be reported. The portion of the rectum receiving 100 and 120% of the prescribed dose must be limited to 10 and 5 mm length, respectively.

Prostatic intraepithelial neoplasia (PIN) is the histologic lesion most strongly associated with prostate cancer and has been postulated to be a pre-malignant lesion. However, much of the natural history of PIN remains unknown. A more fundamental understanding of the relationship between PIN and invasive tumors at the molecular level is critically needed and represents an important future challenge for investigators. The importance of their recognition are based on the correlation between their presence and the existence of prostatic adenocarcinomas. It seemed significant to us to point out the criteria of the diagnosis and the action to be taken in front of the discovery of such lesions on biopsies in prostate sufferers.

The purpose of these recommendations proposed by the members of the <>, is to provide an informative report for the clinician and the pathologist, in the management of patients with prostate cancer. These recommendations are common to the ADSAP and UICC recommendations on prostate cancer. Standardized forms are recommended to be included in every report.