F. Audenet

Upper urinary tract instillations in the treatment of urothelial carcinomas: a review of technical constraints and outcomes.

ObjectivesThe role of topical upper urinary tract instillation as adjuvant treatment after conservative management of urothelial carcinomas remains unclear. The aim of this article was to review available techniques and protocols proposed to treat urothelial carcinomas of the upper tract (UTUC).MethodsEvidence acquisition on UTUC topical instillations was performed by a Medline search using combinations of the following key words: urothelial carcinomas; upper urinary tract; renal pelvis; ureter; adjuvant therapy; recurrence; bacillus Calmette-Guérin (BCG); mitomycin C. A total of 36 publications were included in analysis.ResultsDifferent approaches have been reported for instillation of the upper tract (UT): percutaneous nephrostomy, retrograde catheterisation and vesico-ureteral reflux. Currently, BCG and mitomycin C are the most commonly agents used for topical treatment of UTUC. A role for BCG in the management of UT carcinoma in situ (CIS) has been demonstrated in retrospective studies, although a definitive efficacy of adjuvant topical therapy after endoscopic resection of Ta/T1 tumours has not yet been proven. No individual study has shown a statistical improvement in survival and recurrence rates.ConclusionCurrently BCG instillation should be considered as first-line treatment for UT CIS managed conservatively in carefully selected patients. The place for adjuvant topical instillation after ablation of Ta/T1 tumours is less evident and should be evaluated on an individual basis.

Potential role of photodynamic techniques combined with new generation flexible ureterorenoscopes and molecular markers for the management of urothelial carcinoma of the upper urinary tract

Study Type – Therapy (case series)

Nephrectomy improves overall survival in patients with metastatic renal cell carcinoma in cases of favorable MSKCC or ECOG prognostic features

OBJECTIVES The role of cytoreductive nephrectomy (CN) in the treatment of patients harboring metastatic renal cell carcinoma (mRCC) has become controversial since the emergence of effective targeted therapies. The aim of our study was to compare the overall survival (OS) between CN and non-CN groups of patients presenting with mRCC in the era of targeted drugs and to assess these outcomes among the different Memorial Sloan-Kettering Cancer Center (MSKCC) and The Eastern Cooperative Oncology Group (ECOG) performance status subgroups. METHODS AND MATERIALS A total of 351 patients with mRCC at diagnosis recruited from 18 tertiary care centers who had been treated with systemic treatment were included in this retrospective study. OS was assessed by the Kaplan-Meier method according to the completion of a CN. The population was subsequently stratified according to MSKCC and ECOG prognostic groups. RESULTS Median OS in the entire cohort was 37.1 months. Median OS was significantly improved for patients who underwent CN (16.4 vs. 38.1 months, P<0.001). However, subgroup analysis demonstrated that OS improvement after CN was only significant among the patients with an ECOG score of 0 to 1 (16.7 vs. 43.3 months, P = 0.03) and the group of patients with good and intermediate MSKCC score (16.8 vs. 42.4 months, P = 0.02). On the contrary, this benefit was not significant for the patients with an ECOG score of 2 to 3 (8.0 vs. 12.6 months, P = 0.8) or the group with poor MSKCC score (5.2 vs. 5.2, P = 0.9). CONCLUSIONS CN improves OS in patients with mRCC. However, this effect does not seem to be significant for the patients in ECOG performance status groups of 2 to 3 or poor MSKCC prognostic group.

Predictive Factors of Oncologic Outcomes in Patients Who do not Achieve Undetectable Prostate Specific Antigen after Radical Prostatectomy

PURPOSE We identified factors predicting oncologic outcomes in cases of persistently detectable prostate specific antigen. MATERIALS AND METHODS We reviewed the charts of patients treated with radical prostatectomy between 1998 and 2011 at a total of 14 centers. Study inclusion criteria were radical prostatectomy for presumed localized prostate cancer, absent positive nodes and detectable prostate specific antigen, defined as prostate specific antigen 0.1 ng/ml or greater 6 weeks postoperatively. Of the 9,735 radical prostatectomy cases reviewed 496 (5.1%) were eligible for analysis. Predictive factors for oncologic outcomes were assessed in time dependent analyses using the Kaplan-Meier method and Cox regression models. RESULTS At 6 weeks prostate specific antigen was 0.1 to 6.8 ng/ml. Biochemical progression was noted in 74.4% of patients and clinical metastasis was noted in 5%. The 2 most powerful predictors of general salvage treatment (vs radiotherapy) were postoperative prostate specific antigen greater than 1 ng/ml (OR 3.46, p=0.032) and prostate specific antigen velocity greater than 0.2 ng/ml per year (HR 6.01, p=0.001). Positive prostate specific antigen velocity was the single factor that independently correlated with the risk of failed salvage therapy (HR 2.6, p=0.001). The 5-year disease-free survival rate was 81.0% in patients with stable or negative prostate specific antigen velocity compared with 58.4% in those with positive prostate specific antigen velocity (p<0.001). CONCLUSIONS Patients with detectable prostate specific antigen after radical prostatectomy have a poor biochemical outcome. We identified postoperative prostate specific antigen and prostate specific antigen velocity as independent predictors of progression and failed salvage treatment. In addition to pathological prognostic factors, these factors should be considered early to better stratify patients for adjuvant therapy.

Hereditary‐like urothelial carcinomas of the upper urinary tract benefit more from adjuvant cisplatin‐based chemotherapy after radical nephroureterectomy than do sporadic tumours

To evaluate the impact of ‘hereditary‐like’ status in upper tract urothelial carcinoma (UTUC) on the survival of patients who have undergone radical nephroureterectomy (RNU) and adjuvant chemotherapy.

Nephron-Sparing Surgery for Renal Tumors Measuring More Than 7 cm: Morbidity, and Functional and Oncological Outcomes

BACKGROUND The purpose of this study was to evaluate morbidity, functional, and oncological outcomes after NSS in renal tumors > 7 cm. MATERIALS AND METHODS We retrospectively analyzed data from 168 patients with tumors > 7 cm who were treated using NSS between 1998 and 2012. RESULTS Imperative and elective indications accounted for 76 (45.2%) and 92 (54.8%) patients, respectively. Major perioperative complications and renal function deterioration occurred in 33 (19.6%) and 51 patients (30.4%), respectively. In multivariate analysis, age older than 60 years (P = .001; hazard ratio [HR], 5) and tumor malignancy (P = .014; HR, 6.7) were prognostic factors for renal function deterioration whereas imperative indication was a risk factor for major postoperative complications (P = .0019; HR, 2.7). In 126 (75%) patients with malignant tumors, after a median follow-up of 30 months (range, 1-254 months), 25 patients (20.2%) died. In multivariate analysis, imperative indication (P = .023; HR, 4.2), positive surgical margin (P = .021; HR, 3.3), and Fuhrman grade > II (P = .013; HR, 3.7) were prognostic indicators for cancer-free survival (CFS). Imperative indication (P = .04; HR, 8.5) and Fuhrman grade > II (P = .04; HR, 3.9) were predictive factors of cancer-specific survival (CSS). In case of elective indication, positive surgical margin, local recurrence, and cancer-related death occurred in 4 (7.6%), 1 (1.1%), and 1 (1.1%) cases, respectively. For elective indication, 5-year estimates of CFS, CSS, and overall survival rates were: 85.7%, 98%, and 93.9%, respectively. CONCLUSION In this selected population, imperative vs. elective indication status seems to play a critical role in oncologic outcomes. Oncologic results for elective indications are close to those reported with radical nephrectomy.

Adrenal tumours are more predominant in females regardless of their histological subtype: a review

ObjectivesAdrenal tumours are a heterogeneous group of rare tumours. The aim of this article was to critically review gender-specific differences in the incidence, prognosis and symptoms of the different subtypes of adrenal tumours.MethodsData acquisition regarding gender differences in adrenal tumours was performed using MEDLINE searches with combinations of the following keywords: adrenal tumours, gender, sex differences, adrenocortical carcinoma, pheochromocytoma, incidentaloma, risk factors and genetic aspects.ResultsData are scarce in the literature concerning the effects of gender on adrenal lesions. Although the incidence of most types of tumours (other than breast cancer and other gender-related tumours) is higher in men than in women, evidence suggests that adrenal tumours (i.e. incidentalomas, adrenal carcinomas, oncocytomas and adrenal cysts) are more frequent in women than in men. In addition, female patients have significantly increased numbers of self-reported signs and symptoms of pheochromocytoma than male patients, irrespective of biochemical phenotype and tumour presentation. Relatively little research has been performed examining the reasons for these disparities. However, hormonal interactions involving complex adrenal, endocrine and neurocrine functions together with variations in hormonal receptor sensitivity have been hypothesised to be involved.ConclusionGender differences exist in the incidence and symptoms of several subtypes of adrenal tumours. The reasons for these disparities are not well established. In addition to epidemiological data, these results need to be further investigated to better understand the role of genetic and hormonal predispositions in the development, behaviour and aggressiveness of adrenal tumours.

Oncologic control obtained after radical prostatectomy in men with a pathological Gleason score ≥ 8: A single-center experience

OBJECTIVE To assess the oncologic control afforded by radical prostatectomy (RP) in high-risk prostate cancers with a Gleason score ≥ 8. MATERIALS AND METHODS We performed a retrospective review of prostate cancer patients who underwent RP between 1995 and 2005 for prostate cancer and who had a pathologic Gleason score ≥ 8. Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml after surgery. RESULTS Overall, 64 patients were included and followed for a median time of 84.3 months. The mean age was 63 ± 5.2 years. The mean preoperative PSA was 11.9 ± 7.3 ng/ml (1.9-31), and 29 patients (46%) had a PSA > 10 ng/ml. The biopsy Gleason score was ≤ 7 for 49 patients (76.6%). After pathologic analysis, there were 25 (39%) stage pT2, 37 (58%) stage pT3, and 2 (3%) stage pT4 patients. Nine patients had lymph node involvement (14%). The surgical margins were positive in 25 patients (39%). In 51 patients, (80%) the Gleason score was underestimated by biopsies: 40 patients with a definitive score of Gleason 8 had a Gleason score of 6 or 7 on biopsies, while 11 patients with a Gleason score of 9 initially, had a Gleason score of 7 or 8. Twenty-seven patients underwent adjuvant treatment: external radiation therapy (n = 19), HRT (n = 3), or both (n = 5). During follow-up, 41 patients (64%) presented with a biochemical recurrence, and 11 (17%) died. The PSA-free survival rate at five year was 44%. CONCLUSION RP remains a possible therapeutic option in certain cases of the high-risk cohort of patients with a Gleason score ≥ 8. However, patients should be warned that surgery might only be the first step of a multi-modal treatment approach. The modalities of adjuvant treatments and the right schedule to deliver it following RP still need to be defined.

Standard or accelerated methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: Does dose intensity matter?

BACKGROUND There is continuing controversy regarding the optimal regimen for neoadjuvant chemotherapy (NAC) in bladder cancer. PATIENTS AND METHODS We performed a retrospective analysis of 241 consecutive bladder cancer patients who received a combination of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) using a standard (52 patients) or an accelerated schedule (189 patients) as NAC before radical cystectomy in 17 centres of the French GEnito-urinary TUmour Group from March 2004-May 2013. RESULTS The median age was 62 years. As expected, the median number of cycles, the median total dose of cisplatin and the median cisplatin dose intensity were higher in patients treated with the accelerated regimen. Conversely, the median duration of chemotherapy was shorter. Regarding toxicity, grade III/IV neutropenia, grade III thrombocytopenia and grade III anaemia as well were more frequently observed in patients treated with the standard regimen. Among 211 (88%) patients who proceeded to cystectomy, 75 (35%) patients achieved an ypT0 pN0 status (no pathologic residual tumour cells) with no significant difference according to the MVAC schedule. Three-year overall survival rates were 66.5% (95% confidence interval [CI], 56-79) and 72% (95% CI, 59.5-88) in the standard and accelerated cohorts, respectively. In the multivariate analysis, two independent prognostic parameters were retained: the ypT0 stage and the ypN0 stage. Heterogeneity test did not show any interaction with NAC regimens. CONCLUSION Similar pathological response and survival rates were observed whatever the chemotherapy regimen used. Haematological toxicity was greater in patients who received standard MVAC.

Prospective assessment and histological analysis of adherent perinephric fat in partial nephrectomies

OBJECTIVES The complexity of partial nephrectomy (PN) is partly anticipated by morphometric tumor-based scores that do not consider patient-related issues such as adherent perinephric fat (APF). Also, the objective is to prospectively assess the predictive factors of APF during PN, its effect on complications, and to correlate it to the histological reality. METHODS A total of 125 consecutive patients undergoing robotic or open PN were prospectively included. The Mayo adhesive probability score (MAP score) was compared to the peroperative presence of APF defined by a score≥2. Adipose tissue was analyzed histologically for fibrosis and inflammatory infiltrate of CD68+macrophages. Univariate and multivariate logistic regression analyses were performed to evaluate predictive factors of APF, and outcomes were compared using chi-square and Kruskal-Wallis tests. RESULTS APF was present in 51 patients (40.8%) and associated with slight longer operating time and increased blood loss. Warm ischemia time, margins, transfusion, and the Clavien-Dindo score were not different. In multivariate analysis, only male sex, age, waist circumference, fat density on computed tomography, and MAP score were significant predictors of APF. A radioclinical score was more predictive of APF than MAP score alone. Histologically, there was no macrophage infiltration but larger adipocytes in APF without significant differences in fibrosis. CONCLUSIONS APF can be accurately predicted using radioclinical data as the MAP score, combined with sex, age, and waist circumference. APF is associated with increased operative time and blood loss without postoperative complications. Histological analysis finds larger adipocytes in APF without inflammatory infiltrate, and no difference in fibrosis.