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.

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.

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.

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.

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.

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).

Mid-term oncological control after laparoscopic radical cystectomy in men: a single-centre experience.

OBJECTIVE: • To assess the mid-term (3 years of follow-up) oncological control of laparoscopic radical cystectomy (LRC) for high-grade muscle-invasive bladder cancer in a well studied male population. PATIENTS AND METHODS: • We assessed 40 men with bladder cancer (mean [range] age 66.5 [50-75] years) who underwent LRC and extended pelvic lymphadenectomy at our institution between April 2004 and September 2008. • Of the 40 patients, 13 (32.5%) had a complete laparoscopic procedure (ileal conduit: seven patients; neobladder: five patients; bilateral ureterostomy: one patient) and 27 (67.5%) had an LRC procedure only (ileal conduit: 15 patients; neobladder: 12 patients). RESULTS: • No major complications were observed intraoperatively. • The mean operating time was 407 min and the mean blood loss was 720 mL. Four patients (10%) required conversion to open surgery. The mean (range) hospital stay was 10.2 (7-25) days. One patient died of myocardial infarction in the postoperative period. • Pathological analysis showed organ-confined tumours (stage pT0/pT1/pT2/pT3a) in 22 patients (55%) and extravesical disease (pT3/pT4) in 18 (45%). Of the 40 patients, six (15%) had lymph node involvement. The mean (range) number of nodes removed was 19.9 (5-40). • At a mean (range) follow-up period of 36 (0-72) months, 26 patients were alive with no evidence of disease (disease-free survival rate 67%). CONCLUSION: • Laparoscopic radical cystectomy is a safe, feasible, and effective alternative to open radical cystectomy (ORC). The 3-year oncological efficacy was comparable with that of ORC.

Low pretreatment total testosterone (< 3 ng/mL) predicts extraprostatic disease in prostatectomy specimens from patients with preoperative localized prostate cancer.

OBJECTIVE: • To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well-studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer. PATIENTS AND METHODS: • A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution. • The results were classified into two groups based on the total serum testosterone: group1, < 3 ng/mL; group 2, ≥ 3 ng/mL. • Student's t-test was used to compare continuous variables, and Fisher's exact test or the chi-squared test was used to compare categorical variables. • Survival curves were established using the Kaplan-Meier method and compared using the log-rank test. In all tests, P < 0.05 was considered to indicate statistical significance. RESULTS: • All patients had localized prostate cancer based on digital rectal examination (DRE) and preoperative magnetic resonance imaging (MRI). Groups 1 and 2 were similar in terms of age, body mass index, preoperative co-morbidities (cardiovascular and diabetes mellitus), clinical stage of prostate cancer and preoperative PSA levels. • In pathological specimens, low total testosterone (< 3 ng/mL) was an independent risk factor for high Gleason score (> 7) and for locally advanced pathological stage (pT3 and pT4). • Higher preoperative testosterone correlated with disease confined to the gland. • There was no association between serum testosterone levels and surgical margin status, on the one hand, and biochemical recurrence on the other. CONCLUSION: • Low serum testosterone appears to be predictive of aggressive disease (Gleason score >7 and extraprostatic disease, pathological stage > pT2) in patients who underwent RP for localized prostate cancer.

Impact of the primary Gleason pattern on biochemical recurrence-free survival after radical prostatectomy: a single-center cohort of 1,248 patients with Gleason 7 tumors.

PURPOSE: We aimed to evaluate the impact of the primary Gleason pattern on biochemical recurrence-free survival (RFS) after radical prostatectomy (RP) in a single-center cohort of patients with Gleason 7 tumors. MATERIALS AND METHODS: From 1998 to 2008, 2,239 consecutive patients underwent RP for a localized prostate cancer. A total of 1,248 patients with Gleason score (GS) 7 cancers were included. Follow-up was standardized for all patients and recorded into a prospective database. Median postoperative follow-up was 23.4 months. Biochemical recurrence was defined by prostate-specific antigen level > 0.2 ng/ml. RESULTS: In all, 721 patients (57.8%) had a final GS of 3 + 4 and 527 (42.2%) of 4 + 3. Patients with GS 4 + 3 had a significantly higher risk of biochemical progression than those with GS 3 + 4 (P < 0.001). The 3- and 5-year biochemical RFS for Gleason score 3 + 4 cancers was 84.6 and 76.4%, respectively, versus 69.9 and 61.1% in Gleason score 4 + 3 cancers. Multivariate analysis showed that the primary Gleason remained statistically predictive for PSA failure (P = 0.018). When analysis was stratified by both pathologic stage and margin status, predictive value of primary Gleason was significant in pT2R0, pT3-4R0, and pT3-4R1 cancers, whereas survival curves were not statistically different in pT2R1 cancers (P = 0.672). CONCLUSION: Primary Gleason 4 pattern is an independent predictor for PSA failure. Analysis of Gleason patterns provides clinically relevant prognostic information, which may assist in the management of patients with Gleason score 7 cancers.

Pathological findings and prostate specific antigen outcomes after radical prostatectomy in men eligible for active surveillance--does the risk of misclassification vary according to biopsy criteria?

PURPOSE: We compared the pathological findings and prostate specific antigen outcome after radical prostatectomy in men eligible for active surveillance according to 3 biopsy inclusion criteria. MATERIALS AND METHODS: The study population included 177 men eligible for active surveillance who fulfilled clinicobiological criteria and biopsy criteria as group 1-less than 3 positive cores and less than 3 mm total tumor length, group 2-less than 3 positive cores with cancer involvement of less than 50% in any core and group 3-less than 33% of positive cores. Prostate specific antigen density cutoffs were also studied in these groups. Pathological findings on radical prostatectomy specimens and biochemical recurrence-free survival were studied. Median followup after radical prostatectomy was 34 months. RESULTS: A majority of Gleason score 6 disease was observed in group 1 (51.7%) whereas a majority of Gleason score 7 or greater disease was reported in groups 2 (53.6%) and 3 (55.4%). Extracapsular extension was noted in 17.5% of radical prostatectomy specimens in group 3 vs 11.2% in group 1 (p = 0.175). The risk of overall unfavorable disease (defined as pT3-4 stage and/or Gleason score 8 or greater) was significantly higher in men with cancer involvement of 3 mm or greater on initial biopsy (27.3% vs 13.5%, respectively, p = 0.023). The 3-year biochemical recurrence-free survival rate was 94.0% and was not affected by the 3 active surveillance definitions. CONCLUSIONS: Even with the use of a 21-core biopsy protocol the rate of unfavorable disease in radical prostatectomy specimens remains increased in men eligible for active surveillance. Patients must be informed of this risk of misclassification which ranges from 20% to 28% in men who fulfill the less stringent biopsy criteria.

The role of tumor-free status in repeat resection before intravesical bacillus Calmette-Guerin for high grade Ta, T1 and CIS bladder cancer.

PURPOSE: We evaluated the outcome of repeat transurethral bladder tumor resection for high risk nonmuscle invasive bladder cancer before induction and maintenance bacillus Calmette-Guerin. MATERIALS AND METHODS: Included in the study were 151 consecutive patients with a mean age of 68.6 years (range 32 to 86) with primary high grade, nonmuscle invasive (Ta, T1 or CIS) bladder cancer. All patients underwent repeat transurethral bladder tumor resection and were shown by repeat resection to be tumor-free or have residual tumor before bacillus Calmette-Guerin. The bacillus Calmette-Guerin response was evaluated by disease recurrence and progression. RESULTS: A total of 70 tumor-free patients and 47 with residual tumor received bacillus Calmette-Guerin induction and maintenance therapy after repeat transurethral bladder tumor resection, of whom 84 (71.8%) were disease-free during followup. In the tumor-free group 11.4% of tumors recurred compared with 27.7% in the residual tumor group (p <0.05). Progression was noted in 5.7% of tumor-free cases vs 17.0% of residual tumor cases (p <0.05). Time to recurrence was significantly less in the residual tumor group than in the tumor-free group (17.8 vs 23.9 months, p <0.001). CONCLUSIONS: Tumor-free status at repeat transurethral bladder tumor resection improves the bacillus Calmette-Guerin response rate and delays tumor recurrence. During followup recurrence in residual tumor-free patients develop more likely as low grade lesions than in patients with residual tumor at repeat transurethral bladder tumor resection.

Pathological findings and prostate-specific antigen outcomes after laparoscopic radical prostatectomy for high-risk prostate cancer.

STUDY TYPE: Therapy (case series) Level of Evidence 4. OBJECTIVE: To review the biochemical recurrence-free survival (RFS) rates of laparoscopic radical prostatectomy (LRP) in patients with a high risk of disease progression as defined by preoperative criteria of D'Amico et al. PATIENTS AND METHODS: Between October 2000 and May 2008, 110 patients had extraperitoneal LRP and bilateral pelvic lymph node sampling for high-risk prostate cancer in our department. High-risk prostate cancer was defined as a prostate-specific antigen (PSA) level of >20 ng/mL, and/or a biopsy Gleason score >or=8, and/or a clinical stage of T2c-T4 stage. The median follow-up was 37.6 months. Risk factors for time to biochemical recurrence were tested using log-rank survivorship analysis and Cox proportional hazards regression. RESULTS: Prostate cancer was organ-confined in 36% of patients; the Overall RFS was 79.4% and 69.8% at 1 and 3 years, respectively. The 3-year RFS rates for organ-confined cancer vs extracapsular extension were 100% and 54.3%, respectively (P < 0.001). The 3-year RFS rates for tumour-free seminal vesicle vs seminal vesicle invasion were 81.8% and 33.6%, respectively (P < 0.001). The 3-year RFS rates for negative surgical margins vs positive were 85.2% and 47.3%, respectively (P = 0.001). Compared with men with any single pathological risk factor or any two risk factors, men with all three risk factors had a significantly shorter time to PSA failure after LRP (log-rank test, P < 0.001). CONCLUSION: Among patients at increased risk of disease progression as defined by preoperative criteria, a third of men with organ-confined disease have a favourable prognosis. Men at high risk for early PSA failure could be better identified by pathological assessment of RP specimens, and selected for phase III randomized trials investigating adjuvant systemic treatment.

Robot-assisted extraperitoneal laparoscopic radical prostatectomy: experience in a high-volume laparoscopy reference centre.

OBJECTIVE: To describe our current procedure of robot-assisted laparoscopic radical prostatectomy (RALP), and to assess the effect of the learning curve on perioperative data, early oncological outcomes and functional results, as RALP has increasingly become a treatment option for men with localized prostate cancer. PATIENTS AND METHODS: In all, 206 consecutive men had a RALP between July 2001 and November 2008 for localized prostate cancer. Among the overall cohort, the 175 men operated on by the same surgeon were distributed into five groups according to the chronological order of the procedures. The mean follow-up after RALP was 18.3 months. Patient demographics, surgical data and postoperative variables were collected into a prospective database. Data were compared by chronological groups into single-surgeon cohort. RESULTS: The median operative time and blood loss were 140 min and 350 mL, respectively. The complication rate was 8.3%. Cancers were pT3-4 in 34.5%. The mean hospital stay and duration of bladder catheterization were 4.3 and 8.2 days, respectively. The rate of positive surgical margins (PSMs) was 17.2% in pT2 cancers. The recovery rate of continence was 98% at 12 months. Intraoperative time, blood loss and length of hospital stay were significantly improved after a short learning curve. The continence recovery, the rate and the length of PSM were also improved beyond the learning curve, but difference was not statistically significant. CONCLUSIONS: RALP is a safe and reproducible procedure and offers a short learning curve for experienced laparoscopic surgeons. Beyond the learning curve, continued experience might also provide further improvements in terms of operative, pathological and functional results.

The effect of prostate-specific antigen screening during the last decade: development of clinicopathological variables independently of the biopsy core number.

OBJECTIVE: To study the development of stage migration in prostate cancer after controlling for the number of biopsy cores. PATIENTS AND METHODS: In all, 1826 patients had a first set of 21-core biopsies taken between 2001 and 2008. Among the 801 patients with prostate cancer, 443 had a laparoscopic radical prostatectomy (RP). Patients were divided into three subsets according to the date of biopsy, i.e. period 1 (2001-2003), period 2 (2004-2005), and period 3 (2006-2008). Study end points were the development over time of: (i) clinico-biological characteristics; (ii) biopsy variables; (iii) pathological RP features; and (iv) the biochemical recurrence-free (RFS) rate after surgery. RESULTS: The mean age decreased significantly over time (P = 0.004). The proportion of men with a prostate-specific antigen (PSA) level of 4-10 ng/mL increased significantly over time at the expense of the proportion of men with a PSA level of ≥ 10 ng/mL (P = 0.004). A biopsy Gleason score of ≥ 7 was reported in 53.9% of period 1, compared to 39.6% in period 3 (P = 0.001). RP specimens had a significantly lower proportion of extraprostatic disease (P = 0.013), of high Gleason scores (P = 0.049), and positive margins (P = 0.011) over time. The RFS curves did not vary over time (P = 897). CONCLUSION: Current candidates for prostate biopsy are younger and have lower PSA levels than those who had biopsies taken at the beginning of the decade. Cancers are less aggressive in terms of Gleason score, extent of the disease on biopsy cores and rate of extraprostatic disease on RP specimens than those diagnosed at the beginning of the decade.