Radioisotope-guided Lymphadenectomy for Pelvic Lymph Node Staging in Patients With Intermediate- and High-risk Prostate Cancer (The Prospective SENTINELLE Study).

PURPOSE: Our aim was to prospectively evaluate the diagnostic accuracy of sentinel lymph node biopsy-guided lymph node dissection compared to extended pelvic lymph node dissection in patients with intermediate- or high-risk prostate cancer. MATERIALS AND METHODS: We conducted a prospective, single-arm, multicenter study at 3 tertiary centers in France between February 2012 and May 2019. Eligible patients had clinically localized intermediate- or high-risk prostate cancer. After intraprostatic injection of (99m)Tc-nanocolloid, the locations of the sentinel lymph nodes were defined by preoperative lymphoscintigraphy. Surgical excision of the sentinel lymph nodes was performed using intraoperative gamma probe guidance. After resection of the sentinel lymph nodes, extended pelvic lymph node dissection was performed in all patients. We assessed the diagnostic accuracy of the sentinel lymph node biopsy method using extended pelvic lymph node dissection as the reference standard. This trial was registered in ClinicalTrials.gov (NCT02732392). RESULTS: A total of 162 men cN0M0 (CT scan and bone scan) were enrolled: 106 (65.4%) and 56 (34.6%) patients had intermediate- and high-risk prostate cancer, respectively. The median number of nodes retrieved was 14 (mean 16, IQR 10-21) per patient. At final pathological analysis, 22 patients (13.6%) were pN+. Sensitivity, specificity, negative predictive value, and positive predictive value of sentinel lymph node biopsy method in detecting patients with at least 1 lymph node metastasis were 95.4% (95% CI, 75.1-99.7), 100% (95% CI, 96.6-100), 99.2% (95% CI, 95.5-99.9), and 100% (95% CI, 80.7-100), respectively. CONCLUSIONS: Our multicenter prospective study supports that sentinel lymph node biopsy is a very effective and sensitive method for pelvic lymph node staging in patients with intermediate- or high-risk localized prostate cancer.

Long-term outcomes of whole gland high-intensity focused ultrasound for localized prostate cancer.

OBJECTIVES: To report the 10-year oncologic and functional outcomes of whole-gland HIFU as first-line treatment for localized prostate cancer (PCa). PATIENTS AND METHODS: Patients were retrospectively included between January 2005 and July 2018 from a prospectively maintained database at a single academic institution. No patient underwent androgen deprivation therapy prior to HIFU. Primary endpoint was biochemical recurrence-free survival (BRFS). Secondary oncological endpoints included salvage treatment-free survival (STFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: A total of 97 patients met our inclusion criteria and were included in the final analysis. According to D'Amico classification, the numbers of patients with low-, intermediate-, and high-risk disease were 38 (39.2%), 52 (53.6%), and 7 (7.2%). A total of 21 (21.6%) patients received salvage treatment at a mean of 4.1 years (± 2.8) after HIFU. The 10-year OS, CSS and BRFS rates were 91.8%, 100% and 40.3% in the overall cohort, respectively. In multivariate analysis, predictive factors for biochemical recurrence were intermediate-risk group (RR = 2.065; 95% CI 1.008-4.230; p = 0.047) and PSA nadir > 0.5 ng/mL (RR = 4.963; 95% CI 2.251-10.947; p < 0.001). Symptoms related to bladder outlet obstruction were the most frequently recorded adverse events. In multivariate analysis, positive biopsy on the prostatic apex was predictor of obstructive complications (RR = 3.2, 95% CI 1.092-9.476, p = 0.034). Only four patients developed severe urinary incontinence (> 1 pad/day). CONCLUSIONS: HIFU showed low PCa-specific mortality, but biochemical recurrence rates were highly variable among patients. Future studies are needed to improve patient selection.

HoSAGE: sarcopenia in older patient with intermediate / high-risk prostate cancer, prevalence and incidence after androgen deprivation therapy: study protocol for a cohort trial.

BACKGROUND: Sarcopenia is defined by a loss of muscle strength associated to a decrease in skeletal muscle mass. Ageing greatly contributes to sarcopenia as may many other factors such as cancer or androgen deprivation therapies (ADT). This cohort study aims to evaluate (1) the prevalence of muscle disorders and sarcopenia in older patients before initiation of intermediate to high risk prostate cancer treatment with ADT and radiotherapy, and (2) the occurrence and/or aggravation of muscle disorders and sarcopenia at the end of cancer treatment. METHODS: This cohort study is monocentric and prospective. The primary objectives are to determine the risk factor of sarcopenia prevalence and to study the relationship between ADT and sarcopenia incidence, in patients 70 years and older with histologically proven localized or locally advanced prostate cancer, addressed to a geriatrician (G8 score ≤14) for comprehensive geriatric assessment (CGA) in Marseille University Hospital. Secondary objectives encompass, measurement of sarcopenia clinical criteria along prostate oncological treatment; evaluation of the quality of life of patients with sarcopenia; evaluation of the impact of socio-behavioral and anthropological factors on sarcopenia evolution and incidence; finally the evaluation of the impact of ADT exposure on sarcopenia. Sarcopenia prevalence was estimated to be between 20 and 30%, therefore the study will enroll 200 patients. DISCUSSION: The current guidelines for older patients with prostate cancer recommend a pelvic radiotherapy treatment associated to variable duration (6 to 36 months) of ADT. However ADT impacts muscle mass and could exacerbate the risks of sarcopenia. Our study intends to assess the specific effect of ADT on sarcopenia incidence and/or worsening as well as to estimate sarcopenia prevalence in this population. The results of this cohort trial will lead to a better understanding of sarcopenia prevalence and incidence necessary to further elaborate a prevention plan. TRIAL REGISTRATION: The protocol was registered to the French drug and device regulation agency under the number 2019-A02319-48, before beginning the study (11/12/2019). The ClinicalTrials.gov identifier is NCT04484246, registration on the ClinicalTrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04484246 ).

Efficacy of HIVEC in patients with high-risk non-muscle invasive bladder cancer who are contraindicated to BCG and in patients who fail BCG therapy.

PURPOSE: To evaluate Hyperthermic-Intra-Vesical Chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (RFS) rate and bladder preservation rate in patients with High-risk Non-Muscle Invasive Bladder Cancer (NMIBC) who fail BCG therapy or are contraindicated to BCG. METHODS: Between June 2016 and October 2019, patients treated with HIVEC for mostly high-risk NMIBC who failed BCG or BCG-naive if BCG contraindicated have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it. RESULTS: Fifty-three patients, median age 72 [39-93] years, were included in this study (n = 29 BCG-failure and n = 24 BCG-naive). The median follow-up was 18 months. The bladder preservation rate was 92.4%. The 12 months-RFS rate was 60.5%. The RFS rates for BCG-naive and BCG-failure groups were respectively 70% and 52.2% at 12 months. Three patients progressed to muscle infiltration, all in the BCG-failure group and all in the very high-risk EORTC group. Two of them developed metastatic disease and died from bladder cancer. CONCLUSION: Chemohyperthermia using HIVEC achieved a RFS rate of 60% at 1 year and enabled a bladder preservation rate of 92%. Given the low risk of progression in the BCG-naive group, HIVEC could be a good alternative. Conversely, for patients with very high-risk tumors that fail BCG, cystectomy should remain the standard of care and HIVEC may be discussed cautiously for patients who are not eligible for surgery and well informed of the risk of progression to muscle-invasive disease.

Active Surveillance for Biopsy Proven Renal Oncocytomas: Outcomes and Feasibility.

OBJECTIVES: To report the outcomes and feasibility of active surveillance (AS) of biopsy-proven renal oncocytomas. METHODS: Multicentric retrospective study (2010-2016) in 6 academic centers that included patients with biopsy-proven renal oncocytomas who were allocated to AS (imperative or elective indication) with a follow-up ≥1 year. Imaging was performed at least once a year, by CT-scan or ultrasound or MRI. Conversion to active treatment (surgical excision or ablative treatment) was at the discretion of the urologist. The primary endpoint was renal tumor growth (cm/year). Secondary outcomes included accuracy of biopsy, incidence, and reason to change AS to active treatment. RESULTS: Eighty-nine patients were included: Median age 67 years (26-89) and median tumor size 26 mm [15-90] on diagnosis. During a mean follow-up of 43 months'' (median 36 [12-180]), mean tumor growth was 0.24 cm/year. No predictive factors (demographical, radiological or histologic) of tumor growth could be identified. Conversion from AS to active treatment occurred in 24 patients (27%) (13 surgical excisions, 11 ablative procedures), in a median time of 45 (12-76) months'' after diagnosis. Tumor growth was the main indication to convert AS to active treatment (58%) with 8% of the patients opting to discontinue AS. No patient had metastatic progression nor disease-specific death. The correlation between biopsy and surgical specimen was 92%. CONCLUSION: Active surveillance for biopsy-proven renal oncocytomas was oncologically safe and patient adherence was high. No predictive factor for tumor growth could be identified but the tumor growth rate was low, and biopsy efficacy was high.

Efficacy and Safety of Surgery for Benign Prostatic Obstruction in Patients with Preoperative Urinary Catheter.

Purpose: To evaluate the efficacy and safety of benign prostatic obstruction (BPO) surgery in patients with preoperative urinary catheterization. Patients and Methods: We conducted a multi-institutional retrospective study including all patients who failed a trial without catheter (TWOC) after acute urinary retention (AUR) between January 2017 and January 2019. Patients with neurogenic bladder, prostate cancer, or urethral stricture were excluded from the analysis. Patients underwent either monopolar/bipolar transurethral resection of the prostate (TURP), photoselective vaporization of the prostate (PVP), prostate artery embolization (PAE), open prostatectomy (OP), or endoscopic enucleation. The primary endpoint was 12-month urinary catheter-free survival without using benign prostatic hyperplasia medications. Results: One hundred seventy-one consecutive men (median age: 71 years; median prostate volume: 75 cm3) underwent BPO surgery, including 48 (28%) TURP, 62 (36.3%) PVP, 21 (12.3%) endoscopic enucleation, 15 (8.8%) PAE, and 25 (14.6%) OP. The median duration of preoperative urinary catheterization was 69 days (interquartile range 46-125). The 12-month urinary catheter-free survival rate was 84.8% (145/171). Satisfactory voiding returned to 121 patients (70.8%). On backward stepwise multivariable analysis, PVP (odds ratio [OR] 0.27 [0.10-0.69]; p = 0.008), PAE (OR 5.27 [1.28-27.75]; p = 0.03), endoscopic enucleation (OR 0.08 [0-0.49]; p = 0.023), OP (OR 0.10 [0.01-0.57]; p = 0.034), Charlson score (OR 1.36 [1.14-1.66]; p = 0.001), and number of preoperative TWOC failure (OR 2.53 [1.23-5.51]; p = 0.014) were significantly associated with catheter-free survival. Conclusions: In this multi-institutional retrospective study, including patients with preoperative catheterization, the overall success rate of BPO surgery was 70.8% after 1-year follow-up. Compared with TURP, enucleation methods and PVP were associated with better catheter-free survival, whereas PAE was associated with higher risk of AUR recurrence.

Selective Trans-arterial Embolization of Iatrogenic Vascular Lesions Did Not Influence the Global Renal Function After Partial Nephrectomy.

OBJECTIVE: To evaluate the renal function outcomes after selective trans-arterial embolization (SAE) of iatrogenic vascular lesions (IVL), including pseudoaneurysm and arteriovenous fistula, following partial nephrectomy (PN). MATERIALS AND METHODS: A multi-institutional study was conducted including consecutive patients who underwent PN between January 2009 and March 2019. Two surgical approaches were used: open and robot-assisted PN. Patients with SAE were identified and matched (1:2) with patients without IVL. The matching criteria were age, gender, Charlson score, creatinine clearance, RENAL score, and tumor size. The primary outcome was the evolution of global renal function at 6-months postoperatively. RESULTS: A total of 493 consecutive PN (360 open PN and 133 robot-assisted PN) were included. IVL occurred in 17 cases (3.4%) without statistical difference according to the surgical approach (P = .78). Patients from embolization group were matched to 34 cases without postoperative IVL. Groups were comparable concerning clinical, tumor and surgical characteristics. The clinical success of SAE, defined as the absence of recourse to a second embolization or a total nephrectomy, was obtained in 16 (94.1%) cases. No minor or major complications were reported after SAE. The preoperative estimated glomerular filtration rate (eGFR) was similar between control group (93 [85-102] ml/min) and embolization group (95 [83-102] ml/min) (P = .99). Median (IQR) eGFR between control group (87 [72-95] ml/min) and embolization group (83 [76-93] ml/min) at a follow-up of 6 months showed no significant difference (P = .73). CONCLUSION: IVL are rare complications of PN. SAE is an effective and minimally invasive management tool, with no deleterious effect on global renal function.

Impact of Androgen Deprivation Therapy Associated to Conformal Radiotherapy in the Treatment of D'Amico Intermediate-/High-Risk Prostate Cancer in Older Patients.

PURPOSE/OBJECTIVE: The association of 3D Conformal External Beam Radiotherapy (3D-CEBRT) with adjuvant Androgen Deprivation Therapy (ADT) proved to treat patients with intermediate- and high-risk localized prostate cancer (IR and HR). However, older patients were underrepresented in literature. We aimed to report the oncological results and morbidity 3D-CEBRT +ADT in ≥80 years patients. MATERIAL AND METHODS: From June 1998 to July 2017, 101 patients ≥80 years were included in a tertiary center. The median age was 82 years. ADT was initiated 3 months prior 3D-CEBRT in all patients, with a total duration of 6 months for IR prostate cancer (group A; n = 41) and 15 months for HR prostate cancer (group B; n = 60). Endpoints included overall survival (OS), metastasis-free survival (DMFS), biochemical recurrence-free survival (BRFS) and toxicity. RESULTS: Five years-OS was 95% and 86.7% in groups A and B, respectively. Cardiovascular events occurred in 22.8% of ≥80 years patients with no impact on OS. In the multivariate analysis, age <82 years, Karnofsky index and normalization of testosterone levels were significantly associated with better OS. CONCLUSION: Age ≥80 years should not be a limitation for the treatment of IR and HR prostate cancer patients with 3D-CEBRT and ADT, but cardiovascular monitoring and prevention are mandatory.

Diagnostic ureteroscopy prior to nephroureterectomy for urothelial carcinoma is associated with a high risk of bladder recurrence despite technical precautions to avoid tumor spillage.

PURPOSE: There have recent reports in the literature of increased rates of bladder recurrence (BR) after radical nephroureterectomy (RNU) when diagnostic flexible ureteroscopy (DFU) was performed before RNU. The technical heterogeneity of DFU was a major bias in these studies. Our purpose was to evaluate the impact of a standardized DFU technique before RNU on the risk of BR. METHODS: A retrospective monocenter study including patients who underwent RNU for upper tract urothelial carcinoma (UTUC) between 2005 and 2017. 171 patients were identified. 78 patients were excluded owing to a history of bladder cancer before RNU or neo-adjuvant/adjuvant chemotherapy. 93 included patients were stratified according to pre-RNU ureteroscopy (DFU + 70 patients) or no pre-RNU ureteroscopy (DFU-23 patients). The standardized DFU technique consisted of systematic ureteral sheath (ch9-10), flexible ureteroscopy, biopsy, and drainage with a mono-J/bladder catheter to avoid contact of contaminated urine of the upper tract with the bladder. RESULTS: Epidemiological, initial staging, and postoperative tumoral characteristics were similar in both groups. Mean follow-up was 35 months [2-166], 47(50%) BR occurred with 41(87%) in the DFU + group, and pre-RNU-DFU was an independent predictive factor of BR (OR = 4[1.4-11.9], P = 0.01) (Cox regression model). The characteristics of BR were similar in both groups, although BR occurred earlier in DFU + (427 days vs. 226 days (P = 0.07)). CONCLUSION: Bladder recurrence after diagnostic ureteroscopy + nephroureterectomy was high despite technical precautions to avoid contact of bladder mucosa with contaminated urine from the upper urinary tract. Post-DFU endovesical instillation should be investigated.

Comparison between Zumsteg classification and Briganti nomogram for the risk of lymph-node invasion before radical prostatectomy.

PURPOSE: To evaluate the performance of the Zumsteg classification to estimate the risk of lymph-node invasion (LNI) compared with the Briganti nomogram (BN) in prostatectomy patients with intermediate-risk prostate cancer (IRPC). METHODS: We included consecutive patients who had extended pelvic lymph-node dissection associated with radical prostatectomy for IRPC. To be classified favorable intermediate risk (FIR), patients could only have one intermediate-risk factor, fewer than 50% positive biopsies and no primary Gleason score of 4. RESULTS: On the 387 patients included, 149 (38.5%) and 238 (54.3%) were classified FIR and unfavorable intermediate risk (UIR), respectively, and 212 (54.8%) had a BN inferior to 5%. Thirty-eight patients (9.8%) had LNI: 6 FIR patients (4.0%) versus 32 UIR patients (13.4%) and 14 patients (6.6%) with a BN inferior to 5% versus 24 patients (13.7%) with a BN superior to 5%. Eight patients with a BN inferior to 5%, but classified UIR, had LNI. Sensitivity to detect LNI was higher with the Zumsteg classification than with the BN: 84.2% (CI 95% [68-93]) versus 63.2% (CI 95% [46-78]). Both screening tests were concordant to predict LNI (kappa coefficient of 0.076, p < 0.05 for Zumsteg and Briganti) CONCLUSIONS: Zumsteg classification appeared to be more sensitive and as effective (despite the impossibility to make decision curve analysis) than the BN to estimate the risk of LNI. Regarding the modest number of pN+ patients, further studies are needed to see the interest of proposing ePLND for UIR patients only.

Extent of positive surgical margins following radical prostatectomy: impact on biochemical recurrence with long-term follow-up.

BACKGROUND: To assess the prognostic value of the extent of positive surgical margins (PSM) following radical prostatectomy (RP) on biochemical recurrence (BR) with long-term follow-up. METHODS: This retrospective study analyzed 1275 RPs performed between January 1992 and December 2013 in two university centers in Marseille (France). The inclusion criteria were: follow-up > 24 months, undetectable postoperative prostate-specific antigen (PSA), no seminal vesicle (SV) invasion, no lymph node invasion confirmed by surgery (pN0) or imaging (pNx), and no neoadjuvant or adjuvant treatment. BR was defined by PSA level ≥ 0.2 ng/mL on two successive samples. We included 189 patients, divided into two groups: - Focal PSM (fPSM): single PSM (sPSM) ≤3 mm; - Extensive PSM (ePSM): sPSM with linear length > 3 mm or several margins regardless of the length. RESULTS: The median follow-up was 101 months (18-283) and the median age was 63 years (46-76). BR occurred in only 12.1% (14/115) of cases involving fPSM and in 54.1% (40/74) of cases involving ePSM. In the multivariate model, ePSM patients were significantly associated with increased BR compared to fPSM (hazard ratio [HR] = 6.11; 95% confidence interval [CI] = 3.25-11.49). The ePSM significantly decreased BR-free survival (p < 0.001) for every patient and every subgroup (pT2, pT3a, pG ≤6, and pG ≥7). The median BR time following RP was significantly shorter for ePSM patients than fPSM (57.2 vs. 89.2 months p < 0.001). CONCLUSION: With a median 8-year follow-up, ePSM was strongly associated with BR compared to fPSM. Therefore, it seems legitimate to monitor patients with fPSM. In cases of ePSM, adjuvant treatment appears effective.

Criteria for indication and treatment modification in a cohort of patients with prostate cancer treated with hormone therapy.

BACKGROUND: No published studies have specifically assessed whether treatment modifications to androgen deprivation therapy (ADT) for prostate cancer (PCa) are frequently carried out in routine clinical practice. The current study was conducted to determine what proportion of patients who had initiated hormone therapy with a gonadotropin-releasing hormone (GnRH) analogue then had their treatment regimen modified during the first 24 months. METHODS: A prospective, noninterventional study was carried out in routine clinical practice in France. Patients with locally advanced or metastatic PCa were followed up for 2 years after treatment initiation with a GnRH analogue. The primary endpoint was the proportion of patients with a modification to their initial hormone therapy. RESULTS: In total, 1301 patients were enrolled into the study by 204 physicians, and the primary endpoint could be evaluated for 891 patients. The GnRH analogue treatment was initiated for metastatic PCa (24.2%), locally advanced PCa without planned local treatment (20.6%), locally advanced PCa in association with radiotherapy (31.6%), and biochemical recurrence after local treatment (21.4%). Hormonal treatment was modified in 43.8% (390/891) of patients during the 24-month follow-up period after GnRH analogue initiation. In 61.3% of cases (239/390), the type of modification involved a change of GnRH analogue formulation or switch to another GnRH analogue. A total of five significant predictive factors for GnRH analogue treatment modification were identified: metastatic stage; physician sector; physician speciality; presence or absence of urinary symptoms; and intermittent versus continuous ADT. CONCLUSIONS: This study shows that in 43.8% of the patients with advanced PCa, ADT is modified in the first 2 years after initiation in routine clinical practice. Predictive factors for alteration of ADT were metastatic stage and the choice of an intermittent schedule.

The visual prostate symptom score is a simple tool to identify and follow up in general practice patients with lower urinary tract symptoms associated with benign prostatic hyperplasia (a study with 1359 patients).

INTRODUCTION: The IPSS (International Prostate Symptom Score), a structured self-administered questionnaire is the reference test for evaluation of lower urinary tract symptoms (LUTS). A 5-pictogram score entitled Score Visuel Prostatique en Images (SVPI) was proposed in France and evaluated by urologists. We assessed the interest of the SVPI for the identification and monitoring of benign prostatic hyperplasia (BPH)-related LUTS in general practice, and compared it with the IPSS. METHODS: A prospective observational survey was carried out with general practitioners (GPs) throughout France. The first 4consecutive patients aged over 60years, with BPH-related LUTS (IPSS score greater than 8) for whom the GP freely intended to prescribe an alpha-blocker, were enrolled. Two self-administered questionnaires were used at baseline and at follow-up visit (between 1 and 3months): French language version of the IPSS (8questions) and the SVPI. The 5pictograms of the SVPI were: How many times do you urinate during the day (score of 0 to 5)? How many times do you urinate during the night (score of 0 to 5)? Do you experience an urgent need to urinate (score of 0 to 4)? How strong is the stream (response from 0 to 4)? Do you urinate in a satisfactory manner (score of 0 to 6)? The primary objective was to assess and validate the sensitivity to change of the SVPI at baseline and follow-up visit by the study of the correlation of its changes according to the changes of LUTS evaluated with the IPSS. RESULTS: Five hundred and forty seven GPs enrolled at least one patient and returned information. 2261patients completed the inclusion questionnaire, and 1359 were included in the statistical analysis. Under treatment with alpha-blocker, the IPSS average decreased from 17.7±4.9 to 10.5±4.4 (P<0.0001) with an average diminution of 7.2±4.0, which corresponded to an improvement of 40.7%. This significant decrease of the IPSS involved all its components. The total SVPI was evaluated to 13.8±3.1, the irritative sub-score to 7.4±2.0, and the obstructive sub-score to 2.4±0.8. The internal consistency of the SVPI was good with a value of the Cronbach Alpha coefficient of 0.74. Under treatment with alpha-blocker, the value of the total SVPI decreased from 13.8±3.1 to 8.2±3.0 (P<0.0001) between enrolment and the follow-up visit. The Pearson coefficients assessing the correlations in 1359 patients with benign prostatic hypertrophy were statistically significant at enrolment, and at the follow-up visit. Their variations were all significant. The correlations were weak for the obstructive subscores. Four hundred and fifty-one GPs gave their opinion on the SVPI compared to IPSS: for 36.8% of them, the SVPI was completed a little more rapidly than the IPSS, for 34.6% more rapidly, and for 22.8% of them the SVPI was completed much more rapidly. For 5.8% of them, there was no difference. With regard to ease of understanding for the patient, the 451 GPs responded: much easier for 27.3%, easier for 37.3%, a little easier for 27.1%, and 8.4% had no opinion. CONCLUSION: This study showed the SVPI to be a simple and useful tool for identifying and monitoring BPH-related LUTS. Total SVPI was correlated with total IPSS, even if the obstructive subscore correlation was weaker. The good sensitivity of the SVPI to change showed its potential interest for monitoring LUTS. Given the underuse of the IPSS and the interest expressed by GPs and urologists, the SVPI might be used alone to analyse patient complaints.

Selection criteria for initiation and renewal of luteinizing hormone-releasing hormone agonist therapy in patients with prostate cancer: a French prospective observational study.

OBJECTIVES: To define the profile of patients with prostate cancer (PCa) receiving a 3-month or 6-month formulation of luteinizing hormone-releasing hormone (LHRH) agonist in France and the reasons for choosing between formulations. METHODS: This prospective 1-year observational study included patients with PCa starting LHRH agonist therapy in everyday practice. Reasons for prescription and patient preference were recorded at inclusion, 3 or 6 months, and 12 months. The percentage of patients with a renewed initial prescription was recorded during follow up. RESULTS: A total of 1438 patients with PCa were included. Hormonotherapy was initiated more frequently with a 6-month (n = 903; 62.8%) than with a 3-month formulation (n = 535; 37.2%). The initial prescription was renewed in most patients after 3 or 6 months (86.1%) and 12 months (71%); 170 patients switched from a 3-month to a 6-month formulation during follow up. Presence of metastases influenced initial prescription (odds ratio 0.439; 95% confidence interval 1.095-1.892), with a 3-month formulation more often prescribed than a 6-month formulation to men with metastatic PCa at diagnosis (21.3% versus 15.8%, respectively). The most frequent reasons given by physicians for choosing the 6-month formulation were 'simplification of therapeutic regimen' (86.9%) or 'fewer unnecessary visits' (46.8%). Similar reasons were given for switching from a 3-month to a 6-month formulation during follow up. The most frequent reasons given by physicians to initiate therapy with a 3-month formulation were 'usual practice/habit' (55.5%) or 'closer patient management' (46.2%). 'Closer patient management' and 'reassuring effect upon patient' were the main reasons for switching from a 6-month to a 3-month formulation during follow up. Approximately 80% of patients were satisfied with the formulation they were prescribed and patients' reasons for preferring one formulation over another were similar to the physicians' reasons for prescribing these formulations. CONCLUSIONS: Slow-release formulations of LHRH agonists are useful therapies for physicians treating patients with PCa and there may be a preference for the 6-month formulation.

Quality of life of 1276 elderly patients with prostate cancer, starting treatment with a gonadotropin-releasing hormone agonist: results of a French observational study.

This French observational, longitudinal, prospective study described the health-related quality of life (HRQoL) of elderly men (≥75 years old) with prostate cancer after initiating gonadotropin-releasing hormone (GnRH) agonist therapy. At baseline and 3-6 months after baseline, European Organisation for Research and Treatment of Cancer quality of life questionnaire-core 30 (QLQ-C30) and prostate-specific (QLQ-PR25) questionnaires were completed by patients. Data from 1276 patients were analyzed. At baseline, mean (±SD) age was 80 (±4.1) years, 29.1% of patients had Gleason scores ≥8 and 24.9% had metastases. At baseline, increasing age, presence of metastasis and presence of comorbidity had a negative impact on QLQ-C30 and QLQ-PR25 scores. At follow-up, improvement in emotional-functioning (2.8; p < 0.001), social-functioning (1.7; p = 0.011), global HRQoL (1.6; p = 0.029), sleep-disturbance (-2.1; p = 0.011), appetite-loss (-4.0; p < 0.001) and pain (-4.1; p < 0.001) QLQ-C30 scores were observed. In addition, there was a worsening in treatment-related symptom (8.6; p < 0.001), sexual-activity (-5.5; p < 0.001) and sexual-functioning (-22.6; p < 0.001) QLQ-PR25 scores, and an improvement in urinary symptoms (-3.7; p < 0.001) and incontinence aid (-2.9; p = 0.023) QLQ-PR25 scores. This study shows that, apart from the expected impact on sexual functioning domains, HRQoL is not adversely affected by 3-6 months of GnRH agonist therapy in older men with prostate cancer.

External validation of the Heidenreich criteria for patient selection for unilateral or bilateral retroperitoneal lymph node dissection for post-chemotherapy residual masses of testicular cancer.

OBJECTIVE: To validate the Heidenreich criteria for patient selection for unilateral retroperitoneal lymph node dissection (RPLND) for residual masses after chemotherapy for nonseminomatous germ cell tumor (NSGCT). SUBJECTS/PATIENTS AND METHODS: For validation, the data of 59 patients who underwent RPLND for residual masses of NSGCT were used. Of these patients, 23 (39 %) qualified for a modified RPLND, the others had an indication for a bilateral dissection. Results from histopathology after RPLND and follow-up data for relapse inside or outside the zone of the resection template were considered for validation. RESULTS: In the study cohort, median age at time of RPLND was 31 years. The 2-year disease-free survival was 90 and 96 % for the bilateral and the unilateral RPLND patients, respectively. Overall, 8 (14 %) relapses were observed after a median follow-up of 54 month. Of these, 6 were outside of the resection field and 2 were in-field. Of the 23 patients with indication for a modified RPLND, 1 patient relapsed in the contralateral testis and 1 inside the modified RPLND template. No relapse was observed outside the modified RPLND field and inside the untouched contralateral RPLND field. The Heidenreich criteria did therefore not misclassify a single patient. CONCLUSION: The Heidenreich criteria for the selection of candidates for unilateral RPLND for residual masses after chemotherapy allow a highly reliable selection of patients. The application of the Heidenreich criteria can help to reduce comorbidity and invasiveness of RPLND.

Adrenomedullin blockade suppresses growth of human hormone-independent prostate tumor xenograft in mice.

PURPOSE: To study the role of the adrenomedullin system [adrenomedullin and its receptors (AMR), CLR, RAMP2, and RAMP3] in prostate cancer androgen-independent growth. EXPERIMENTAL DESIGN: Androgen-dependent and -independent prostate cancer models were used to investigate the role and mechanisms of adrenomedullin in prostate cancer hormone-independent growth and tumor-associated angiogenesis and lymphangiogenesis. RESULTS: Adrenomedullin and AMR were immunohistochemically localized in the carcinomatous epithelial compartment of prostate cancer specimens of high grade (Gleason score >7), suggesting a role of the adrenomedullin system in prostate cancer growth. We used the androgen-independent Du145 cells, for which we demonstrate that adrenomedullin stimulated cell proliferation in vitro through the cAMP/CRAF/MEK/ERK pathway. The proliferation of Du145 and PC3 cells is decreased by anti-adrenomedullin antibody (αAM), supporting the fact that adrenomedullin may function as a potent autocrine/paracrine growth factor for prostate cancer androgen-independent cells. In vivo, αAM therapy inhibits the growth of Du145 androgen-independent xenografts and interestingly of LNCaP androgen-dependent xenografts only in castrated animals, suggesting strongly that adrenomedullin might play an important role in tumor regrowth following androgen ablation. Histologic examination of αAM-treated tumors showed evidence of disruption of tumor vascularity, with depletion of vascular as well as lymphatic endothelial cells and pericytes, and increased lymphatic endothelial cell apoptosis. Importantly, αAM potently blocks tumor-associated lymphangiogenesis, but does not affect established vasculature and lymphatic vessels in normal adult mice. CONCLUSIONS: We conclude that expression of adrenomedullin upon androgen ablation in prostate cancer plays an important role in hormone-independent tumor growth and in neovascularization by supplying/amplifying signals essential for pathologic neoangiogenesis and lymphangiogenesis. Clin Cancer Res; 19(22); 6138-50. ©2013 AACR.

[Pharmaco and diet based prostate cancer prevention]. / Pharmaco-prévention et nutri-prévention des cancers de la prostate.

In 2010, in France, 8,790 men died from prostate cancer despite a low and decreasing mortality rate. The individual risk/benefit ratio of prostate cancer screening is the focus of controversy and currently not in favor of a systematic screening program. Therefore, only prevention could reduce incidence, side effects of treatment and related mortality. Interestingly, prostate cancer prevention is also a field of controversy mainly about 5-alpha-reductase inhibitors. However, it could be expected that pharmaco- or diet-based prevention will be a huge tool for cancer control, even more for prostate cancer burden. This review comprehensively analyses which molecules or compounds could be used in preventive trials. With regard to pharmaco-prevention, three different kinds of drugs could be identified. First drugs, which aim at mainly or even solely reduce prostate cancer risk such as 5-alpha-reductase inhibitors and selective estrogen receptor modulators. Drugs, which aim at wider preventive impact such as: nonsteroidal anti-inflammatory drugs or difluoromethylornithine. Lastly, drugs for which reducing prostate cancer incidence is merely a side effect such as statins, metformin or histones desacetylase inhibitors. With regard to diet-based prevention, two main approaches could be identified: aliments and nutriments, on one hand, and vitamin and minerals, on the other. Interestingly if compounds reach experimental plausibility, natural foods or even global diet seem to have a higher impact. Lastly, besides assessment of efficacy, effectiveness required the critical step of compliance, which might actually be the weakest link of the prevention chain.

[Radical prostatectomy in prostate cancer: indications and surgical approaches]. / Indications et voies d'abord de la prostatectomie radicale dans le cancer de la prostate.

Prostate cancer is the most frequent in men: 71000 new cases were diagnosed in France in 2011. Early diagnosis allows treatments with curative intent. Risk groups by D'Amico classification system were validated to estimate progression risk after radical prostatectomy, external beam radiotherapy and brachytherapy. Radical prostatectomy is one of the reference treatments for localized prostate cancer. There are many surgical approaches: open retropubic approach, perineal, trans peritoneal or extra peritoneal laparoscopic approach, robotic assisted or not. Main surgical steps are the same between retropubic or laparoscopic approaches. Regarding oncologic (positive surgical margins rate, progression free survival) and functional results (continence and erections), no difference was reported between different surgical approaches.

Seminal vesicle invasion: what is the best adjuvant treatment after radical prostatectomy?

OBJECTIVE: • To evaluate the biochemical-failure free survival according to different adjuvant treatments in patients who underwent radical prostatectomy (RP) with seminal vesicle invasion (SVI). PATIENTS AND METHODS: • Between 1994 and 2008, 4090 men underwent RP in nine centres. Of these, 310 men had a SVI. • Exclusion criteria were: detectable postoperative prostate-specific antigen, lymph node metastases and follow-up <18 months. • Therefore, the study group included 199 patients. Of these, 41 received adjuvant radiotherapy (RT) only, 26 received adjuvant androgen deprivation therapy (ADT) only, 50 received adjuvant ADT combined with RT and 82 were monitored. The endpoint for this analysis was biochemical no evidence of disease (bNED). • Preoperative prostate-specific antigen level, specimen Gleason score, age, clinical stage, surgical margin status and adjuvant treatment were evaluated in a multivariable analysis with respect to bNED survival. RESULTS: • After a mean (range) follow-up of 60.3 (18-185) months, 88 (44.2%) patients had a biochemical relapse. • The estimated 5- and 7-year bNED survival were 32.6% and 25.9% for the observation group, 44.4% and 28.6% for the RT only group, 48.4% and 32.3% for the ADT only group and 82.8% and 62.1% for the adjuvant ADT combined with RT group. • On multivariate analysis, only adjuvant ADT combined with RT (P < 0.001) was an independent prognostic factor of biochemical relapse. CONCLUSIONS: • RP appeared to be insufficient as a single treatment for patients with SVI. • The findings of the present study suggest that adjuvant ADT combined with RT after RP for patients with SVI confers a substantial benefit on 5-year bNED survival.