Clinical recommendations in the management of advanced prostate cancer: International Gastrointestinal, Liver and Uro-oncology (IGILUC 2019) experts.

PURPOSE: Advancements in the diagnosis and treatment of prostate cancer (PC) have rapidly progressed through the past years. Various factors should be taken into account while treating individual patients to ensure optimal and careful decision making. The purpose of this consensus review is to summarize the current practice patterns when managing patients with advanced prostate cancer (APC) as there is still a lack of or very limited evidence on its clinical management in some areas. METHODS: Pre-defined questions were shared with experts prior to the consensus session that took place in Cairo, Egypt in April 2019 during the 8th International gastrointestinal, liver and uro-oncology conference (IGILUC). Voting was based mainly on the expert opinions of the panel after a thorough discussion and review of available evidence from guidelines or best evidence available concerning the topic at hand. RESULTS: A strong consensus or unanimity was reached on 47% of the proposed questions. Notably, the panelists reached consensus on several topics based on high-level expert opinion. These findings contribute in several ways to our understanding of the management of PC and provide a basis for future recommendations. There was also a lack of consensus on other several topics, which suggests the need for further supporting data addressing these knowledge gaps. CONCLUSION: This review offers a thorough understanding of APC practice and offers insight on the various opinions shared amongst experts in the field that can serve as guidance regionally and deepens our understanding of disease management globally.

Ten year experience of retroperitoneal laparoscopic resection for pheochromocytomas: A dual-centre study of 72 cases.

PURPOSE: To evaluate the safety and efficacy of retroperitoneal laparoscopic resection in patients with pheochromocytoma in a retrospective study. METHODS: Clinical data of patients with adrenal and extra-adrenal pheochromocytomas, operated on between September 1998 and September 2008 at two institutions, including information on patient demographics, surgical procedure, complications and hospital stay were retrieved. RESULTS: Seventy-two retroperitoneal laparoscopic resections were performed (68 patients, 30 males/38 females). Mean age was 51.4 years (15-87 years). Four patients had a bilateral pheochromocytoma. Median BMI was 27 kg/m(2) (interquartile range 23-29). Mean tumour diameter was 4.6 cm (1.3-9). Thirteen patients had a tumour >6 cm. Mean operation time was 110 min (40-210), and median blood loss during surgery was 160 ml (0-1200 ml). Duration of surgery significantly increased with BMI (p = 0.004) and tumour size (p = 0.004). Four patients required conversion to open surgery (two bleeding, one severe adhesion to inferior vena cava and one renal artery aneurysm). Five patients required a blood transfusion with minor postoperative complications in three patients. Major perioperative haemodynamic variations (systolic blood pressure > 180 mmHg, diastolic blood pressure < 70 mmHg) were observed in 54 % of patients, 30 % required postoperative adrenergic drug treatment. The only predictive factor of a perioperative haemodynamic complication was the high level of normetanephrine in the preoperative blood samples. The median postoperative hospital stay was 4.5 days. Blood loss, postoperative complication and postoperative hospital stay did not increase in patients with tumours >6 cm. CONCLUSION: Retroperitoneal laparoscopic surgery for pheochromocytoma is reproducible, safe and effective.

Predicting the risk of harboring high-grade disease for patients diagnosed with prostate cancer scored as Gleason ≤ 6 on biopsy cores.

PURPOSE: Biopsy and final pathological Gleason score (GS) are inconstantly correlated with each other. The aim of the current study was to develop and validate a predictive score to screen patients diagnosed with a biopsy GS ≤ 6 prostate cancer (PCa) at risk of GS upgrading. METHODS: Clinical and pathological data of 1,179 patients managed with radical prostatectomy for a biopsy GS ≤ 6, clinical stage ≤ T2b and preoperative PSA ≤ 20 ng/ml PCa were collected. The population study was randomly split into a development (n = 822) and a validation (n = 357) cohort. A prognostic score was established using the independent factors related to GS upgrading identified in multivariate analysis. The cutoff value derived from the area under the receiver operating characteristic curve of the score. RESULTS: After RP, the rate of GS upgrading was 56.7%. In multivariate analysis, length of cancer per core > 5 mm (OR 2.938; p < 0.001), PSA level > 15 ng/ml (OR 2.365; p = 0.01), age > 70 (OR 1.746; p = 0.016), number of biopsy cores > 12 (OR 0.696; p = 0.041) and prostate weight > 50 g (OR 0.656; CI; p < 0.007) were independent predictive factors of GS upgrading. A score ranged between -4 and 12 with a cutoff value of 2 was established. In the development cohort, the accuracy of predictive score was 63.7% and the positive predictive value was 71.2%. Results were confirmed in the validation cohort. CONCLUSION: This predictive tool might be used to screen patients initially diagnosed with low-grade PCa but harboring occult high-grade disease.

Evaluation of urinary symptoms in patients with post-prostatectomy urinary incontinence treated with the male sling TOMS.

AIMS: To evaluate stress urinary incontinence (SUI), overactive bladder (OAB), and obstructive symptoms in patients with post-radical prostatectomy urinary incontinence (pRP-UI) treated with the bulbar compressive sling TOMS, and investigate the effect of each urinary symptom on urinary bother. MATERIALS AND METHODS: We prospectively followed 40 patients with pRP-UI before, and 6 and 12 months (T6 and T12, respectively) after implantation of the TOMS sling. Urinary symptoms were evaluated using the following questionnaires: USP, ICIQ, UCLA-PCI (urinary bother domain), PGI-I, and daily pad use. Success was defined as patients wearing no pads or using one security pad. RESULTS: Significant improvement of mean USP-SUI (6.97/9, 3.35, 3.02, P < 0.001) and USP-OAB domains (8.1/21, 5.74, 5.71, P < 0.001), ICIQ (15.15/21, 8.17/21, 8.35/21, P < 0.01), urinary bother (92.5/100, 42.5, 41.87, P < 0.001), and pad number (2.78, 1.01, 1.03, P < 0.001) were noted between baseline, T6, and T12. At baseline, 32 (80%) patients reported urge incontinence. Urinary bother strongly correlated with UPS-SUI but not with UPS-OAB score. At T12, 22 (55%) patients with pad use were considered cured, and 13 (32.5%) patients reported a greatly improved urinary tract condition (PGI-I). Improvement of USP-SUI and USP-OAB scores correlated with improvement of ICIQ and PGI scores. The USP-obstructive domain remained unchanged. CONCLUSION: The TOMS sling improves SUI and OAB symptoms without generating obstructive symptoms. OAB symptoms including urge incontinence reported by most patients were not a major concern at baseline; however, improvement of these symptoms was associated with improvement of continence and PGI-I scores.

Regional copy number-independent deregulation of transcription in cancer.

Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.

Location, extent, and multifocality of positive surgical margins for biochemical recurrence prediction after radical prostatectomy.

PURPOSE: To study the prognostic value of extent, number, and location of positive surgical margins (PSM). METHODS: A total of 1,504 consecutive adjuvant treatment naive and node-negative radical prostatectomy men were included in a prospective database including extent, number, and location of PSM. Mean follow-up was 33 months. Endpoint was biochemical progression-free (bPFS) survival. The impact of margin status and characteristics was assessed in time-dependent analyses using Cox regression and Kaplan-Meier methods. RESULTS: PSM was reported in 26.7 % of patients. The predominant PSM locations were apex and posterior locations. Median PSM length was 4.0 mm. The 2-year bPFS was 73.7 % in PSM patients as compared to 93.0 % in NSM patients (p < 0.001). The rate and extent of PSM increased significantly with pathologic stage (p < 0.001). The extent of PSM length was linearly correlated with bPFS (p = 0.017, coefficient: -0.122). In univariable analysis, extent and number of PSM were significantly linked to outcomes. None of PSM subclassifications significantly influenced the bPFS rates in the subgroup of pT2 disease patients. Conversely, stratification by PSM location (apex vs. other locations, p = 0.008), by PSM number (p = 0.006), and by PSM length (p < 0.001) showed significant differences in pT3-4 cancer patients. In that subgroup, PSM length also added to bPFS prediction using PSM status only in multivariable models (p = 0.005). CONCLUSIONS: PSM subclassifications do not improve the biochemical recurrence prediction in organ-confined disease. In non-organ-confined disease, PSM length (≥3 mm), multifocality (≥3 sites), and apical location are significantly linked to poorer outcomes and could justify a more aggressive adjuvant treatment approach.

Concomitant high-grade prostatic intraepithelial neoplasia is associated with good prognosis factors and oncologic outcome after radical prostatectomy.

OBJECTIVES: To assess correlations between concomitant high-grade prostatic intraepithelial neoplasia (HGPIN), pathological features and oncologic outcomes after radical prostatectomy (RP). MATERIAL AND METHODS: We prospectively collected a single-institution database of 2,351 patients who underwent RP between 1998 and 2011. RESULTS: 1,272 (54.1%) patients had HGPIN on specimens. The mean follow-up was 28 months. Presence of HGPIN was significantly associated with a favorable preoperative risk status and with pathological factors of poor prognosis in RP specimens. Patients without HGPIN had a worse biochemical recurrence-free survival compared with those with HGPIN in RP specimen (log-rank test: p = 0.015). The 3-year RFS rate was 73.9% for the HGPIN group versus 67.2%. The absence of HGPIN was also significantly correlated with the use of androgen deprivation treatment during the follow-up (p < 0.001). In Cox multivariate analysis, taking into account the other prognostic pathological factors, HGPIN was not an independent predictive factor for PSA failure (p = 0.868). CONCLUSION: HGPIN is associated with factors of good prognosis but fails to show independent significance when classical pathological prognostic factors are taken into account.

Acute bacterial prostatitis after transrectal ultrasound-guided prostate biopsy: epidemiological, bacteria and treatment patterns from a 4-year prospective study.

OBJECTIVES: To evaluate the incidence, and clinical and bacterial features of iatrogenic prostatitis within 1 month after transrectal ultrasound-guided biopsy for detection of prostate cancer. METHODS: From January 2006 to December 2009, 3000 patients underwent a 21-core transrectal ultrasound-guided prostate biopsy at Henri Mondor Hospital (Créteil, France) and were prospectively followed. All patients had a fluoroquinolone antimicrobial prophylaxis for 7 days. The primary study end-point was to evaluate the incidence of iatrogenic acute prostatitis within 1 month after the biopsy. The secondary end-point was to analyze the clinical and the bacterial features of the prostatitis. RESULTS: Overall, 20 patients of the entire study population (0.67%) had an acute bacterial prostatitis within 2.90 ± 1.77 days (range 1-7 days) after the transrectal ultrasound-guided biopsy. The groups of patients with (n = 20) and without (n = 2980) infection were similar in terms of age, prostate-specific antigen level and prostate volume. Escherichia coli was the only isolated bacteria. The subsequent tests for antibiotic susceptibility showed a 95% resistance for fluroquinolone and amoxicillin. Resistance to amoxiclav, trimethoprim-sulfamethoxazole, third generation cephalosporin and amikacin was 70%, 70%, 25% and 5% respectively. No resistance to imipenem was reported. They were all admitted for treatment without the need of intensive care unit referral. Complete recovery was achieved after 21.4 ± 7 days of antibiotic treatment. CONCLUSIONS: A fluroquinolone-based regimen still represents an appropriate prophylaxis protocol to minimize the risk of acute prostatitis secondary to prostate biopsy. Patients should be provided the appropriate care soon after the onset of the symptoms. An intravenous third generation cephalosporin or imipenem-based therapy seem to provide satisfying results.

External validation of extranodal extension and lymph node density as predictors of survival in node-positive bladder cancer after radical cystectomy.

BACKGROUND: Prognostic factors in pathologic node-positive patients after radical cystectomy are debated. Extranodal extension (ENE) and lymph node density (LND) are strong predictors of survival. The aim of this study was to assess factors predictive of survival and to evaluate the prognostic significance of the tumor, node, metastasis staging system (TNM) nodal classification in a retrospective cohort of node-positive bladder cancers after radical cystectomy. METHODS: We retrospectively reviewed the data of 75 patients with node-positive bladder cancer after radical cystectomy. Node pathological examination was performed by two experienced uropathologists. Cox regression analysis was performed to identify factors predictive of progression. RESULTS: The median number of removed lymph node was 18 (range 3-49). The median number of positive lymph nodes was 3 (range 1-35). Overall progression-free and cancer-specific survival were 5 and 12 %. In multivariate analysis, ENE, LND with a 20 % cutoff, and adjuvant chemotherapy were independent predictors of progression-free survival (p = 0.007, 0.006, <0.0001). Neither the 2002 nor the 2009 TNM nodal classification was associated with recurrence. CONCLUSIONS: ENE and LND are strong predictors of clinical outcome in patients with node-positive bladder cancer treated by cystectomy. The actual TNM classification could probably be improved using these criteria, allowing better prognostic classification of node-positive bladder cancer after radical cystectomy.

Risk of repeat biopsy and prostate cancer detection after an initial extended negative biopsy: longitudinal follow-up from a prospective trial.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Even after a negative set of prostate biopsies, the risk of undetected prostate cancer remains clinically significant. Predictive markers of such a risk are undefined. In addition to PSA and PSAD, low prostate volume and %fPSA are interesting time-varying risk factors and are relevant in biopsy decision-making. OBJECTIVE: To assess prospectively the time-varying risk of rebiopsy and of prostate cancer (PCa) detection after an initial negative biopsy protocol. PATIENTS AND METHODS: Over a period of 10 years, 1995 consecutive patients with initially negative biopsies were followed. Rebiopsies were performed in patients who had a persistent suspicion of PCa. Predictive factors for rebiopsy and for PCa detection were tested using univariate, multivariate and time-dependent models. RESULTS: A total of 617 men (31%) underwent at least one rebiopsy after a mean follow-up of 19 months. PCa detection rates during second, third, and fourth sets of biopsies were 16.7, 16.9 and 12.5%, respectively. The overall rate of detected PCa was 7.0%. The 5-year rebiopsy-free and PCa-free survival rates were 65.9 and 92.5%, respectively. Indications for rebiopsy were more frequently reported in patients having a high prostate-specific antigen (PSA) level (P = 0.006) or a high PSA density (PSAD; P < 0.001) and in younger patients (P = 0.008). The risk of PCa on rebiopsies was not correlated with age, but significantly increased more than twofold in cases of PSA >6 ng/mL, PSAD >0.15 ng/mL/g, free-to-total PSA ratio (%fPSA) <15, and/or prostate volume <50 mL. Time-dependent analyses were in line with these findings. The main study limitation was the lack of control of the absence of PCa and PSA kinetics in men not rebiopsied. CONCLUSIONS: The overall risk of detected PCa after an initial negative biopsy was low. In addition to PSA and PSAD, which are well-used in rebiopsy indications, low prostate volume and %fPSA are interesting time-varying risk factors for PCa on rebiopsy and could be relevant in biopsy decision-making.

Analysis of outcomes after radical prostatectomy in patients eligible for active surveillance (PRIAS).

OBJECTIVE: To identify the risk of failure of active surveillance (AS) in men who had the Prostate Cancer Research International: Active Surveillance (PRIAS) criteria and had undergone radical prostatectomy (RP), by studying as primary endpoints the risk of unfavourable disease in RP specimens (stage >T2 and/or Gleason score >6) and of biochemical progression after RP. PATIENTS AND METHODS: We assessed 626 patients who had the PRIAS criteria for AS defined as T1c/T2, PSA level of ≤10 ng/mL, PSA density (PSAD) of <0.2 ng/mL per mL, Gleason score of <7, and one or two positive biopsies. All patients underwent immediate RP at our department between January 1991 and December 2010. Multivariate logistic regression was used to test factors correlated with the risk of unfavourable prostate cancer. The risk of progression was tested using multivariate Cox regression models. Biochemical recurrence-free survival (BFS) was established using the Kaplan-Meier method. RESULTS: Pathological study of RP specimens showed upstaging (>T2) in 129 patients (20.6%), upgrading (Gleason score >6) in 281 (44.9%) and unfavourable disease in 312 patients (50%). There was a statistically non-significant trend for BFS at P = 0.06. Predictors of favourable tumours were age <65 years (P = 0.005), one vs two positive biopsies (P = 0.01) and a biopsy core number >12 (P = 0.005). Preoperative factors predicting disease progression were a PSAD of >0.15 ng/mL(2) (P = 0.008) and biopsy core number of ≤12 (P = 0.017). CONCLUSIONS: Even with stringent AS criteria, the rate of unfavourable disease remains high. Predictive factors of unfavourable disease and biochemical progression should be considered when including patients in AS protocols.

Patient selection and pathological outcomes using currently available active surveillance criteria.

OBJECTIVES: To establish the rate of higher risk criteria in various definitions of an active surveillance population. PATIENTS AND METHODS: Over a period of 10 years, 1161 patients were diagnosed with prostate cancer and underwent radical prostatectomy at our institution. Statistical analysis was performed comparing the rates of upgrading, extracapsular extension, seminal vesical involvment and unfavourable disease (Gleason score upgrading >6 and/or T3 disease) for six groups of patients eligible for the University of Toronto, Royal Marsden, John Hopkins, University of California San Francisco, Memorial Sloan Kettering Cancer Center and Prospective Randomized International Active Surveillance. RESULTS: Active surveillance protocols including patients with biopsy Gleason score 3+4 (Royal Marsden) had significantly higher rates of extracapsular extension (P = 0.009), upgrading to pathological Gleason >3+4 (P = 0.004) and unfavourable disease (P = 0.001) compared to the most stringent John Hopkins criteria. Unfavourable disease was found in more than 40% of patients in all series with no significant difference between the Gleason 6 protocols. Biochemical recurrence-free survival at 5 and 10 years was 76.7% and 63.3% for the entire cohort. Positive margins (P < 0.001), pT3 tumours (P = 0.006) and unfavourable disease (P < 0.001) were significant predictors of biochemical recurrence. CONCLUSIONS: Active surveillance in patients with Gleason 3+4 presents a risk of missing unfavourable disease and should be limited to older patients with comorbidities. The differences in inclusion criteria between Gleason 6 protocols did not have a significant impact on the pathological results.

Sexual quality of life in women partnered with men using intracavernous alprostadil injections after radical prostatectomy.

INTRODUCTION: The effects of intracavernous alprostadil injection (IAI), a primary treatment for post-radical prostatectomy (RP) erectile dysfunction (ED) (pRPED), on the sex life of women partnered with men who have undergone RP have received little attention. AIMS: The aim of this study is to investigate the sexual quality of life in female partners of men receiving IAIs for pRPED. METHODS: We retrospectively studied the sex lives of 152 women partnered with men who were being treated for pRPED with IAI and previously had normal erectile function. Women completed the Index of Sexual Life (ISL) questionnaire 1 year after their partner's RP. Male patients completed the International Index of Erectile Function (IIEF-15), the Erection Hardness Score (EHS) questionnaire, the International Consultation on Incontinence Questionnaire (ICIQ), and the UCLA Prostate Cancer Index (UCLA-PCI) urinary function questionnaire. Penile pain was assessed using the visual analog scale (VAS). Statistical analysis was performed using t-tests, Spearman correlation, and multiple linear regression. MAIN OUTCOME MEASURES: Female sexual life satisfaction (SLS), sexual drive (SD), and general life satisfaction (GLS) were assessed using the ISL questionnaire. RESULTS: Mean ages for the 104 couples included were 62.3 and 59.8 years for the men and women, respectively. Mean ISL, SD, SLS, and GLS scores at 12 months were 25.4, 3.8, 14.1, and 7.5, respectively. ISL scores were strongly correlated with IIEF-15 domains, mainly erectile function (r > 0.41, P < 0.00002) and intercourse satisfaction (r > 0.27, P < 0.005). Age and VAS, ICIQ, and UCLA-PCI scores were negatively correlated with some ISL domains. IIEF-15 erectile function and intercourse satisfaction were the most significant domains predicting female SLS. An IIEF-15 erectile function of 25 corresponded to a 75% chance of an SLS score ≥18. CONCLUSION: Indexes of female sexual quality of life were low overall but were highly correlated with the partner's response level to IAI treatment. IAI-related pain, increased age, and poor urinary function of the male partner appear to negatively impact female sex life.

Extraperitoneal robot-assisted laparoscopic radical prostatectomy: a single-center experience beyond the learning curve.

OBJECTIVES: To report our surgical technique and outcomes after extraperitoneal robot-assisted laparoscopic radical prostatectomy (RALRP). MATERIALS AND METHODS: At Henri Mondor's Hospital, we performed the first RALRP in 2001 and started to perform routinely RALRP since 2006. Preoperative characteristics, perioperative parameters, functional and oncological outcomes were collected in a prospective database and studied. All parameters were tested in patients undergoing RALRP beyond the learning curve of each surgeon. The overall cohort included 792 patients. RESULTS: RALRP offers interesting results in terms of hospital stay, operative time, and blood loss. The overall rate of complications was low, especially concerning the rates of anastomosis' complications. An extraprostatic extension was seen in 42.8 % of specimens. The overall rate of positive margins was 30.7 % of specimens. In our cohort, after a mean follow-up of 19 months, 8.7 % of PSA failure has been reported. The rate of continence was 77.4 % at 6 months and 96.8 % at 2 years. The rate of potency was 17 % at 3 months and 60.9 % at 2 years. The 2-year rate was 86.7 % in case of intrafascial dissection. A trifecta outcome was achieved in 44 and 53 % of men at 12 and 24 months, respectively. CONCLUSIONS: The extraperitoneal approach confers interesting results in terms of perioperative parameters as previously described in series using a transperitoneal approach. Functional outcomes in terms of continence and potency recovery after extraperitoneal seem equivalent to those reported after transperitoneal RALRP. Longer follow-up is warranted to confirm our favorable mid-term oncologic outcomes.

Contemporary pathologic characteristics and oncologic outcomes of prostate cancers missed by 6- and 12-core biopsy and diagnosed with a 21-core biopsy protocol.

PURPOSE: To assess the pathological and the oncologic outcomes of the prostate cancer (PCa) missed by 6- and 12-core biopsy protocols by using a reference 21-core scheme. MATERIALS AND METHODS: Between 2001 and 2009, all patients who had PCa detected in an initial 21-core TRUS biopsy scheme and were treated by a radical prostatectomy (RP) were included. Patients were sorted in 3 groups according to the diagnosis site: sextant (6 first cores; group 1), peripheral zone (12 first cores; group 2) or midline/transitional zone (after 21 cores; group 3). Demographics, pathological features in biopsy and RP specimens and follow-up after RP were analyzed. The 5-year progression-free survival (PFS) was studied in the 3 groups. RESULTS: During the study period, 443 patients were included. Among them, 67, 23.7 and 9.2% were, respectively, diagnosed in groups 1, 2 and 3. Among PCa diagnosed in midline/transition zone cores, 42% were intermediate or high risk. Unfavorable disease was more frequently reported in group 1 in terms of extraprostatic extension (P = 0.001), high Gleason score (P = 0.001) and progression (P = 0.001). No significant difference was observed between groups 2 and 3 in terms of pathological features in RP specimens and oncologic outcome. The 5-year PFS was 89.7% and not significantly different in patients diagnosed with a 12-core scheme compared to those diagnosed only with 21-core scheme (P = 0.332). CONCLUSIONS: Our findings emphasize that PCa diagnosed only in a 21-core protocol is at least as aggressive as PCa detected in a 12-core scheme. This study invalidates the widespread idea sustaining that cancers diagnosed by more than 12 biopsies are less aggressive.

A switch from GnRH agonist to GnRH antagonist in castration-resistant prostate cancer patients leads to a low response rate on PSA.

PURPOSE: At the time of castration resistance, it is recommended to realize hormonal manipulations before chemotherapy. We evaluated the impact of a switch from GnRH agonist to antagonist in patients with castration-resistant prostate cancer on PSA and testosterone levels at 3 months. METHODS: Retrospectively, 17 patients from 5 different centers undergoing androgen deprivation therapy and presenting rising PSA confirmed on 3 blood samples 2 weeks apart and despite a castrate testosterone level (<0.5 ng/ml) were reviewed. Antiandrogen withdrawal syndrome had been tested before the switch. Degarelix was administered as followed: 240 mg for the first injection and then 80 mg every month, subcutaneously. We evaluated the PSA and testosterone level variation 3 months after the switch. Patients who experienced a variation in PSA of less than 10% compared to the baseline or who had a more than 10% PSA decrease were defined as responders. RESULTS: Mean PSA level at the switch was 34.3 ± 50.3 ng/ml, with a mean testosterone level of 0.21 ± 0.13 ng/ml. Three months after the switch, mean PSA level was 59.9 ± 81.6 ng/ml (P = 0.061), with a mean testosterone level of 0.19 ± 0.08 ng/ml (P = 0.086). At 3 months, 4 patients (23%) responded to therapy. Thirteen patients (77%) experienced a rise in PSA of more than 10% compared to baseline; 41% of patients decreased their testosterone level. The limitations of this study are its retrospective nature and the limited number of patients. CONCLUSION: Switch from an agonist to an antagonist of GnRH has a limited impact on PSA at 3 months in castration-resistant prostate cancer patients.

Transforming growth factor ß-receptor II protein expression in benign prostatic hyperplasia is associated with prostate volume and inflammation.

OBJECTIVE: To assess transforming growth factor ß-receptor II (TGFBRII) protein expression in benign prostatic hyperplasia (BPH) using immunohistochemistry analysis, and to compare the analysis with phenotypic properties. METHODS: TGFBRII protein expression was profiled using three clinical outcome tissue microarrays (TMAs), sampled from 231 patients who underwent surgery for BPH. Using these TMAs, five inflammatory cell markers were also assessed, including CD3, CD4, CD8, CD20, and CD163. The surgical procedure was open prostatectomy in 95 patients and transurethral resection of the prostate in 136 patients. RESULTS: TGFBRII protein expression was found in BPH epithelium cells for both basal and secretory cells, as well as in fibromuscular stromal cells. TGFBRII staining was also strong in most of the lymphocytes infiltrating the prostate. TGFBRII stromal staining was found to be significantly associated with prostate volume (P = 0.04), whereas TGFBRII epithelial staining was found to be significantly associated with 5-α-reductase-inhibitor medical therapy received by patients before surgery (P = 0.004). Both stromal and epithelial TGFBRII staining were found to be associated with CD4 T-lymphocyte infiltrate, independently of prostate volume (P < 0.001 and P = 0.002). CONCLUSIONS: TGFBRII protein expression in BPH is associated with prostate gland volume and with CD4 T-lymphocyte prostatitis. TGFBRII might be a promising therapeutic target to prevent prostate enlargement or even to decrease prostate volume.

Prospective evaluation of combined oncological and functional outcomes after laparoscopic radical prostatectomy: trifecta rate of achieving continence, potency and cancer control at 2 years.

OBJECTIVE: To determine the proportion of patients who are continent, potent and cancer-free (trifecta rate) 2 years after extraperitoneal laparoscopic radical prostatectomy (ELRP). PATIENTS AND METHODS: We included patients who underwent an ELRP at our department and who were followed for at least 2 years. Those who were impotent or incontinent before the surgery were excluded from the analysis. Overall, 911 men were included. All patients prospectively completed objective, self-administered questionnaires before the medical visit, concerning their voiding and sexual disorders, before surgery and 12 and 24 months after ELRP. Biochemical recurrence was defined as any detectable serum PSA (≥ 0.2 ng/mL). Potency was defined as the ability to achieve an erection sufficient for penetration with or without the use of phosphodiesterase-5 enzyme inhibitor. Urinary continence was defined as absence, or occasional use, of a pad for anticipated vigorous activity. The primary study endpoint was the trifecta rate (cancer control, continence and potency) at 2 years after the surgery. Factors associated with the trifecta outcome were assessed in univariate analysis. RESULTS: Median age and PSA level were 62.2 years and 9.9 ng/mL, respectively. A trifecta outcome was achieved in 29.7 and 54.4% of patients at 12 and 24 months, respectively. The 2-year trifecta rate reached 63.5% in patients undergoing bilateral nerve-sparing surgery and 73.5% in men aged < 60 years. Age < 60 years, PSA level < 10 ng/mL, organ-confined disease and bilateral nerve-sparing procedure were significantly associated with the 2-year trifecta outcome. A total of 84.8% of patients were both cancer-free and continent at 24 months, regardless of erectile function. CONCLUSIONS: Two years after ELRP, the trifecta outcome is achieved in 54.4% of patients who remained potent and continent. This rate reaches 63.5% in patients undergoing a bilateral nerve-sparing procedure. Combined results of good cancer control and continence recovery are reported in 84.8% of patients, regardless of erectile function.

Magnetic resonance imaging does not improve the prediction of misclassification of prostate cancer patients eligible for active surveillance when the most stringent selection criteria are based on the saturation biopsy scheme.

UNLABELLED: Study Type - Diagnostic (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: • To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS). PATIENTS AND METHODS: • We identified prostate cancers patients who had undergone a 21-core biopsy scheme and fulfilled the criteria as follows: prostate-specific antigen (PSA) level ≤ 10 ng/mL, T1-T2a disease, a Gleason score ≤ 6, <3 positive cores and tumour length per core <3 mm. • We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery. • The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion. RESULTS: • Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases. • The rate of unfavourable disease (pT3-4 and/or Gleason score ≥ 4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%). MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314). • In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen. • After a mean follow-up of 29 months, the recurrence-free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1-T2 disease (P = 0.853). CONCLUSION: • The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21-core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high-risk and/or non organ-confined disease in a RP specimen.

Impact of positive surgical margins on prostate-specific antigen failure after radical prostatectomy in adjuvant treatment-naïve patients.

STUDY TYPE: Therapy (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? Despite excellent surgical cancer control, up to 40% of patients will have biochemical recurrence following radical prostatectomy (RP) for localized prostate cancer. Positive surgical margins (PSM) have been clearly demonstrated to be one of the main predictive factors for biochemical failure, disease progression and cancer mortality. However, decision of further management (adjuvant or salvage therapy) in patients with PSM remains controversial, and many debatable questions arise concerning the incidence of clinical progression and the impact of systematic adjuvant treatment on the cancer specific and overall survival. Analysis of the pathological and disease recurrence outcomes of our large cohort of patients treated by RP provides evidence that PSMs are associated with a poor prognosis in terms of PSA failure and need for salvage therapy. However, such a distinction between negative or positive margin cancers seems to appear clinically less relevant in locally advanced disease with seminal vesicle or high Gleason score≥8 due to the predominant significance of these two poor prognosis factors for prediction of PSA failure. OBJECTIVE: To study the impact of positive surgical margins (PSMs) as an independent predictor of prostate-specific antigen (PSA) failure after radical prostatectomy in adjuvant treatment-naïve patients. PATIENTS AND METHODS: From 2000 to 2008, 1943 men who underwent a radical prostatectomy at Henri Mondor Hospital and who did not receive neoadjuvant or adjuvant therapy were included. Follow-up was recorded into a prospective database. Mean follow-up was 68.8 months. The biochemical recurrence-free survival (RFS), defined by a PSA>0.2 ng/mL, and the need for salvage therapy in univariate and multivariate models, were evaluated. RESULTS: PSA failure was reported in 14.7% and PSMs were noted in 25.6%. In the overall cohort, PSM was significantly predictive for PSA failure (P<0.001; hazard ratio, HR, 2.6), need for salvage therapy (P<0.001; HR, 2.9) and specific deaths (P=0.006; HR, 3.7). The 5-year RFS was 84.4% in men with negative margins compared to 57.5% in the case of PSM. After stratification by pathological stage and Gleason score, margin status was significantly predictive for PSA failure in pT2 (P<0.001), pT3a (P=0.001) and/or Gleason score≤7 cancers (P<0.001), whereas the impact of PSM did not reach significance in pT3b (P=0.196), pT4 (P=0.061) and/or Gleason score≥8 cancers (P=0.115). CONCLUSIONS: PSMs are associated with a poor prognosis in terms of RFS and the need for salvage therapy. Such a distinction between negative or positive margin cancers appears to be clinically less relevant in locally advanced disease with seminal vesicle or high Gleason score (≥8).