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Background: The optimal therapeutic strategies for patients with metastatic hormone-sensitive prostate cancer (mHSPC) followed by metastatic castrate-resistant prostate cancer (mCRPC), in terms of cost and effectiveness, remains unknown. This study aims to compare the cost-effectiveness of various potential strategies, from the start of first-line treatment in mHSPC to the death of the patients., Methods: Two Markov decision-analysis models were developed, one for cohort A "asymptomatic/mildly symptomatic patients in mCRPC", and one for cohort B "symptomatic patients in mCRPC". Each strategy reflects daily practice for mHSPC until progression in mCRPC from the start of first treatment regimen with either docetaxel or abiraterone acetate plus prednisone (AA) in mHSPC to the death of the patient. The cost-effectiveness analysis was performed from the French public health care system perspective. Only direct medical costs were included. Survival data were extracted from results of published randomized clinical trials., Results: For cohort A, docetaxel followed by AA is the most cost-effective therapeutic strategy (€96,925 for 4.24 life-years). For cohort B, docetaxel followed by docetaxel is the most cost-effective therapeutic strategy (€81,463 for 4.05 life-years). Sensitivity analyses confirmed the robustness of our results except for a price reduction of 70% for AA or enzalutamide., Conclusion: Our approach is innovative to the extent that our analysis considers various potential strategies for metastatic prostate cancer (mPC). Our economic evaluation suggests that a price reduction of AA or enzalutamide impacts on the results. This approach must continue, including new drugs for patients with mPC., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To define guidelines for the management of localized prostate cancer (PCa) in kidney transplant (KTx) candidates and recipients., Method: A systematic review (Medline) of the literature was conducted by the CTAFU to report prostate cancer epidemiology, screening, diagnosis and management in KTx candidates and recipients with the corresponding level of evidence., Results: KTx recipients are at similar risk for PCa as general population. Thus, PCa screening in this setting is defined according to global French guidelines from CCAFU. Systematic screening is proposed in candidates for renal transplant over 50 y-o. PCa diagnosis is based on prostate biopsies performed after multiparametric MRI and preventive antibiotics. CCAFU guidelines remain applicable for PCa treatment in KTx recipients with some specificities, especially regarding lymph nodes management. Treatment options in candidates for KTx need to integrate waiting time and access to transplantation. Current data allows the CTAFU to propose mandatory waiting times after PCa treatment in KTx candidates with a weak level of evidence., Conclusion: These French recommendations should contribute to improve PCa management in KTx recipients and candidates, integrating oncological objectives with access to transplantation., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: The goal of our study was to describe general practitioner's (GP) practice regarding prostate cancer screening, the prescribing of prostate MRI and to investigate the factors associated with the prescribing of prostate MRI (pMRI)., Methods: A survey was addressed to 1127 GP of the "Bourgogne-Franche Comté" region before the new CCAFU's guidelines publication., Results: 93 practitioners responded, giving a response rate of 8.3%. Eighty GP (86%) responded performing prostate cancer screening. The main means used were the assaying of PSA alone (23 practitioners, 28.8%) or the combination of PSA dosage and digital rectal examination (36 practitioners: 45%). It should be noted that 31 practitioners (39%) did not perform digital rectal examination as part of prostate cancer screening. Thirty two physicians prescribed pMRIs (34.5%.) before any urological consultation. The main indications were several abnormal PSA assays (27 GP, 84.4%) and/or suspicious rectal examination (15 GP, 46.9%). The main reason of this prescription was the gain of time for patient or urologist. Screening was carried out independently of the demographic characteristics of the physicians interviewed. Similarly, the prescription of prostate MRI was not related to the achievement of prostate cancer screening or the screening methods used., Conclusion: It seems that the prescription of pMRI has already become part of the prescribing habits of a number of general practitioners., Level of Evidence: 4., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Introduction: Currently, about 50% of newly prostate cancers are localized and low-risk according to D'Amico risk classification. Focal therapies whose objective is to treat only the index lesion appear as a new alternative being evaluated in the management of these cancers. Besides the interest in the control of the disease, focal therapies present a very low risk of morbidity. Vascular targeted photodynamic therapy (VTP) is one of these new emerging therapies., Method: An exhaustive review concerning VTP in prostate cancer was carried out. A search by the following keywords "low-risk prostate cancer", "focal treatment", "vascular targeted photodynamic therapy" "TOOKAD" was carried out in Pubmed and Embase., Results: In phase II studies, VTP showed a rate of 80% negative biopsies at 6 months, with good clinical tolerance. The European phase III, randomized prospective study, comparing VTP to active surveillance showed a lower proportion of progression, as well as a more significant duration before progression for VTP. The adverse events are mostly moderate and transient. The quality of life of patients is preserved, with a moderate impact on erectile and urinary functions., Conclusion: VTP appear to be a promising new approach in localized low-risk prostate cancer., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: To review biology and management of oligometastatic prostate cancer., Material and Methods: Relevant publications were identified through Medline (www. ncbi.nlm.nih.gov), Embase (www.embase.com) and the US National Library of Medicine (www.clinicaltrials.org) databases using the following keywords, alone or in association, «prostate cancer; metastasis; oligo-metastasis». Articles were selected according to methods, language of publication and relevance. After careful selection 99 publications were eligible for our review., Results: Oligometastatic prostate cancer is a new entity including prostate cancer with a limited number of metastasis. This particular state becomes more frequent with the imaging progresses especially with the common use of new PET imaging with Choline or PSMA. There is no consensus about a strict definition of oligometastatic prostate cancer, number and sites of metastasis vary widely in the literature. Moreover, oligometastatic state can be observed de novo at the time of prostate cancer diagnosis as well as in case of recurrence after a primary treatment. There is actually an important lack of evidence-based medicine and no guidelines regarding treatment can be found. In de novo oligo-metatastatic prostate cancer, treatment of the primary tumor in association with androgen deprivation therapy seems to increase survival in selected patients but this needs to be confirmed by ongoing prospective clinical trials. In recurrent prostate cancer, metastasis directed therapy with or without androgen deprivation therapy is now routinely performed but its impact needs also to be analyzed., Conclusion: In absence of consensus or guidelines, management of prostate cancer should be an individualized, patient-based management taking into account primary tumor stage and grade, number and types of metastasis and patient characteristics., (© 2019 Elsevier Masson SAS. Tous droits réservés.)

Purpose: Vascular targeted photodynamic therapy with TOOKAD® is a new therapeutic option for localized prostate cancer management. The objectives of this study were to assess the feasibility of radical prostatectomy after vascular targeted photodynamic therapy and describe functional and oncologic outcomes., Materials and Methods: We retrospectively included in study 45 patients who underwent salvage radical prostatectomy after vascular targeted photodynamic therapy for recurrent prostate cancer at a total of 14 surgical centers in Europe between October 2008 and March 2017. Of the 42 radical prostatectomies performed 16 were robot-assisted, 6 were laparoscopic and 20 were open surgery. Primary end points were morbidity and technical difficulties. Secondary end points were early and intermediate postoperative functional and oncologic outcomes., Results: Median operative time was 180 minutes (IQR 150-223). Median blood loss was 200 ml (IQR 155-363). According to the surgeons the surgery was easy in 29 patients (69%) and difficult in 13 (31%). Nerve sparing was feasible in 14 patients (33%). Five postoperative complications (12%) were found, including 2 Clavien I, 2 Clavien II and 1 Clavien IIIB complications. Of the cases 13 (31%) were pT3 and 21 (50%) were pT2c. Surgical margins were positive in 13 patients (31%). Prostate specific antigen was undetectable at 6 to 12 months in 37 patients (88%). Nine patients underwent complementary radiotherapy. Four patients had final prostate specific antigen greater than 0.2 ng/ml at a median followup of 23 months (IQR 12-36). At 1 year 27 patients (64%) were completely continent (no pads) and 10 (24%) had low incontinence (1 pad). Four patients (11%) recovered potency without treatment and 23 (64%) recovered potency with appropriate treatment., Conclusions: Salvage radical prostatectomy after vascular targeted photodynamic therapy treatment was feasible and safe without difficulty for most of the surgeons.

Background: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial., Methods: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894., Findings: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients)., Interpretation: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy., Funding: Steba Biotech., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non-symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse. This prospective single-arm open-label phase II study was conducted to evaluate MC regimen in patients with biochemical recurrent PC. MC was planned to be administered orally at a daily dose of 50 mg for 6 months. Primary endpoint was PSA response. Thirty-eight patients were included and treated. Median follow-up was 45.5 months (range 17-100). Among them, 14 patients (37 %) achieved PSA stabilisation and 22 patients (58 %) experienced PSA progression. Response rate was 5 % with one complete response (2.6 %), and 1 partial response with PSA decrease >50 % (2.6 %). The median time until androgen deprivation therapy initiation was around 15 months. The treatment was well tolerated. Neither grade 3-4 toxicity nor serious adverse events were observed. This first prospective clinical trial with MC therapy in patients with non-metastatic biochemical recurrence of PC displayed modest efficacy when measured with PSA response rate, without significant toxicity. It might offer a new safe and non-expensive option to delay initiation of ADT. These results would need to be confirmed with larger prospective randomised trials.

Objective: To determine whether obesity is associated with adverse pathologic characteristics, positive surgical margins and the biochemical recurrence free survival (bRFS) after primary treatment with radical prostatectomy (RP)., Patients and Methods: Medical charts of patients managed with RP between 1999 and 2011 for localized prostate cancer (PCa) were retrospectively reviewed. Population study was split into two groups according to the body mass index (BMI): non obese (BMI< 30 kg/m(2)) and obese (BMI ≥ 30 kg/m(2)). Correlations between obesity and adverse pathological features or bRFS were assessed using univariable and multivariable analyses., Results: Overall, 328 patients were included in the present study: 278 (84.8%) obese and 50 (15.2%) non obese. In multivariable analysis, obesity was associated with positive surgical margins (P=0.014), extracapsular extension (P=0.004) and pathologic Gleason score ≥ 7 (P=0.048). Obesity was not associated with seminal vesicle invasion (P=0.636) and lymph node metastasis (P=0.132). After a mean follow-up of 60.51 ± 28.82 months, no statistical difference in terms of bRFS was observed between the two groups (P=0.186). Furthermore, obesity was not an independent predictor of bFS in multivariable analysis., Conclusion: Obesity was associated with adverse pathologic characteristics and positive surgical margins but no statistical correlation was found with bRFS., Level of Evidence: 5., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Goal: To study the impact of systemic treatment in neoadjuvant strategy before surgery in prostate cancer., Materials: Literature reviews with data analysis from PubMed search using the keywords "neoadjuvant", "chemotherapy", "hormonal therapy", "prostate surgery", "radical prostatectomy", but also reports from ASCO and ESMO conferences. The articles on neoadjuvant treatment before radiotherapy were excluded., Results: First studies with former therapy are more than 15-years-old and with questionable methodology: lack of power to have a clear idea of the impact on survival criteria such as overall survival or relapse-free survival. However, the impact of neoadjuvant hormone therapy on the classic risk factors for relapse (positive margins, intraprostatic disease, positive lymph nodes) was demonstrated by these studies and a Cochrane meta-analysis. The association with hormone therapy seems mandatory in comparison to treatment based solely on chemotherapy and/or targeted therapy. Promising data on the use of new drugs and their combinations arise: abiraterone acetate combined with LHRH analogue showed a fast PSA decrease and higher rates of pathologic complete response. Other results are promising with hormonal blockages at various key points., Conclusion: Studies with 2nd generation anti-androgene agents or enzyme inhibitors seem to show very promising results. To provide answers about the effectiveness of current neoadjuvant strategy in terms of survival, other studies are needed: randomized phase III or phase II exploring predictive biomarkers. The design of such trials requires a multidisciplinary approach with urologists, oncologists, radiologists and methodologists., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objectives: To analyze the impact of the existence of Gleason grade 5 on the adverse pathology and biochemical recurrence-free survival of patients., Patients: Three hundred and seventy-two prostatectomies were performed between 1999 and 2011 in our institution for localised prostate adenocarcinoma. We examined the existence of grade 5 of the specimen to determine the reliability of prostate biopsies in the diagnosis of grade 5 and the association of grade 5 with other histoprognostic factors. Biochemical recurrence-free survival was analyzed according to the presence of grade 5 in the final specimen., Results: In total, all histological data and biochemical recurrence-free survival were available for 321 patients who were included in the study. Sixty-eight had Gleason grade 5 (majority or third minority pattern) on the specimen while 253 had not. Grade 5, rarely diagnosed on biopsy (sensitivity=26.47 %) was correlated independently with the extracapsular extension (OR=2.1; CI 95 [1.1-3.9]), the seminal vesicle invasion (OR=3.8; CI 95 [1.7-8.7]) and positive surgical margins (OR=2.0; CI 95 [1.1-3.6]). Overall survival was similar in both groups but the biochemical recurrence-free survival was statistically lower in the presence of grade 5 (HR=3.7; CI 95 [1.8-7.6]). Biochemical recurrence-free survival was not different than grade 5 is predominant or third minority pattern (HR=1.01; CI 95 [0.3-2.8]). On multivariate analysis, grade 5 was an independent risk factor for biochemical recurrence (P=0.005) as well as seminal vesicle invasion (P=0.047)., Conclusion: The existence of grade 5 in the surgical specimen whatever the percentage was a poor prognostic factor associated with increased tumor aggressiveness and reduced biochemical recurrence-free survival., Level of Evidence: 5., (Copyright © 2014. Published by Elsevier Masson SAS.)

Purpose: The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated., Methods: We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa., Results: Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa., Conclusions: The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.

Bladder outlet obstruction (BOO) is one of the major complication of the locally advanced prostate cancer. Its impact on prostate cancer prognosis is low and remains controversial but its impact on patient quality of life is real. We performed a systematic search to find relevant publications from Medline and wrote a mini-review on the different therapeutic approaches to relieve obstructive symptoms., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Because of the low mortality rates associated with prostate cancer, treatments long-term adverse effects constitute an important parameter in the management of patients. In particular, androgen deprivation has been shown to be linked to several metabolic disorders which are already frequent in men after age 60, such as weight and fat gain, insulin resistance likely to evolve into diabetes, and dyslipidemia. So far no consensus guidelines have been published regarding the screening and treatment of metabolic disorders in men with prostate cancer. It is essential to detect and manage these metabolic disorders, all the more so as they seem to be associated with an increased aggressiveness of prostate cancer. Here we report the development of a new questionnaire, which might contribute to the systematic management, and potentially the screening and treatment or the prevention of these metabolic disorders in patients with prostate cancer. In accordance with recent reviews and on the basis of experience, our French board of experts also recommends systematic screening and selective treatment for diabetes, regular follow-up of fasting glucose rates, lipid profile and blood pressure in all patients under long-term androgen deprivation treatment, as well as lifestyle changes (practice of exercise, nutritional habits)., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Castration resistant prostate cancer occurs when patients experience disease progression despite appropriate hormonal manipulations. In these patients, chemotherapy remains standard treatment. Preclinical and clinical data have demonstrated the potential utility of an immunotherapy-based approach for the treatment of prostate cancer (PC). The phase III trial (IMPACT) has recently reported an advantage for Sipuleucel-T over placebo, with an overall survival 4.1 months superior to placebo. Sipuleucel-T is also the first FDA-approved immunotherapy for prostate cancer. These promising results need to be confirmed with other large studies and within previous step of PC. Neoplasic cells can escape immune responses by multiple mechanisms. A better knowledge of these mechanisms is of major concern for the future development of new immunotherapies approach.

Introduction: The therapeutic approach of prostate cancer depends mainly on pathological criteria obtained through prostate biopsy. The low accuracy of prostate biopsy for Gleason grade determination is well known but its accuracy for bilateral or multifocal tumor has not been evaluated. The goal of this study was to assess the concordance between prostate biopsy and whole prostate specimen obtained after radical prostatectomy especially for bilateral and/or multifocal tumor., Methods: We retrospectively compared the pathological results of prostate biopsy cores to the prostate specimen in patients who underwent radical prostatectomy in our department between the 01/01/1999 and the 31/12/2008. The criteria analyzed were the Gleason score, tumor bilaterality or multifocality. The impact of the number of prostate biopsy cores was also analyzed., Results: Two hundred and five complete histological records were studied. Regarding the Gleason score overall concordance was 55%. In 38%, prostate biopsies downgraded the Gleason score. This concordance decreased with tumor differentiation (90.6% for Gleason 6 vs. 31% for Gleason greater than 7). For the tumor bilaterality, 78% of cancers affected both lobes at the definitive specimen analysis while only 49% were bilateral at prostate biopsies, achieving a concordance of 61%. Multifocal disease was observed in 36% at definitive pathology analysis with low concordance with prostate biopsies (36%). The number of biopsies increased the concordance for the Gleason score (60 to 81% for Gleason 7 and from 28 to 50% for Gleason greater than 7) and tumor location (44 to 70%)., Conclusion: Pathological criteria and tumor mapping obtained from prostate biopsies were not very reliable especially when the tumor was poorly differentiated. An increased number of prostate biopsy core improved the sensitivity and specificity for the Gleason score diagnostic and of the tumor mapping., (Copyright © 2012. Published by Elsevier Masson SAS.)

Background: We conducted a retrospective multi-centre study to determine the characteristics of prostate cancer in renal transplant recipients (RTR) and to analyse the relation with immunosuppressive maintenance therapies., Methods: Patients from 19 French transplant centres diagnosed with prostate cancer at least 1 year after kidney transplantation were included in this study. Data regarding demographics, kidney transplantation, prostate cancer and immunosuppressive treatment were analysed., Results: Sixty-two patients met the eligibility criteria for this study. Thirty-eight patients (61.3%) received calcineurin inhibitors (CNI) and azathioprine (AZA) with or without steroids, twenty received CNI with or without steroids (32.2%) and four received CNI and mycophenolate mofetil (6.5%). Patients with CNI and AZA immunosuppressive therapy presented more high-stage cancer (T3 and T4) when compared to patients receiving CNI alone (47.5% versus 15%, respectively, P = 0.03). A non-significant increase in lymph node invasion was found in patients receiving CNI and AZA compared to patients receiving CNI alone (21% versus 5%, P = 0.16). In the multivariate analysis, the immunosuppressive regimen with CNI and AZA was the only independent risk factor for locally advanced disease (P = 0.007)., Conclusion: Our results showed that RTR are at risk for early occurrence and for locally advanced prostate cancer, especially when they received a CNI and AZA maintenance immunosuppressive therapy.

Introduction: The incidence of genitourinary tumors (GUT) in renal transplant recipients (RTR) is higher than in the general population. We previously reported that CD4 lymphocytopenia is associated with a high incidence of skin cancer in RTR. Here, we investigate whether persistent CD4 T cell lymphopenia is associated with GUT occurrence., Patients and Methods: A total of 433 patients were included in this study. All patients underwent annually systematic lymphocyte subset (CD3, CD4, CD8, CD19) determination by flow cytometry., Results and Conclusion: During the follow-up period, 13 patients developed GUT: 6 patients a prostate adenocarcinoma (incidence 0.06%/year) and 7 patients a renal cell carcinoma (incidence 0.07%/year). The patients with GUT were older than those without. Both groups did not differ in posttransplant duration, dialysis mode and duration, induction regimen, or acute rejection history. No persistent CD4 lymphopenia was observed in the patients with GUT. Although CD4 T cell lymphopenia is associated with skin cancer in long-term RTR, it did not appear to be a risk factor for GUT. This suggests that other factors encountered in the setting of kidney transplantation (e.g., immunosuppressive drugs, end-stage renal failure, etc.) favor the development of GUT in RTR., (2008 S. Karger AG, Basel)