Laurent Zini

Positive Surgical Margin Appears to Have Negligible Impact on Survival of Renal Cell Carcinomas Treated by Nephron-Sparing Surgery

BACKGROUND The occurrence of positive surgical margins (PSMs) after partial nephrectomy (PN) is rare, and little is known about their natural history. OBJECTIVE To identify predictive factors of cancer recurrence and related death in patients having a PSM following PN. DESIGN, SETTING, AND PARTICIPANTS Some 111 patients with a PSM were identified from a multicentre retrospective survey and were compared with 664 negative surgical margin (NSM) patients. A second cohort of NSM patients was created by matching NSM to PSM for indication, tumour size, and tumour grade. MEASUREMENTS PSM and NSM patients were compared using student t tests and chi-square tests on independent samples. A Cox proportional hazards regression model was used to test the independent effects of clinical and pathologic variables on survival. RESULTS AND LIMITATIONS Mean age at diagnosis was 61+/-12.5 yr. Mean tumour size was 3.5+/-2 cm. Imperative indications accounted for 39% (43 of 111) of the cases. Some 18 patients (16%) underwent a second surgery (partial or total nephrectomy). With a mean follow-up of 37 mo, 11 patients (10%) had recurrences and 12 patients (11%) died, including 6 patients (5.4%) who died of cancer progression. Some 91% (10 of 11) of the patients who had recurrences and 83% of the patients (10 of 12) who died belonged to the group with imperative surgical indications. Rates of recurrence-free survival, of cancer-specific survival, and of overall survival were the same among NSM patients and PSM patients. The multivariable Cox model showed that the two variables that could predict recurrence were the indication (p=0.017) and tumour location (p=0.02). No other variable, including PSM status, had any effect on recurrence. None of the studied parameters had any effect on the rate of cancer-specific survival. CONCLUSIONS PSM status occurs more frequently in cases in which surgery is imperative and is associated with an increased risk of recurrence, but PSM status does not appear to influence cancer-specific survival. Additional follow-up is needed.

A critical assessment of the prognostic value of clear cell, papillary and chromophobe histological subtypes in renal cell carcinoma: a population‐based study

To assess the magnitude of the effect of histological subtype (HS, the three most common being clear cell, papillary and chromophobe) on cause‐specific mortality (CSM) from renal cell carcinoma (RCC).

Vascular endocan (ESM-1) is markedly overexpressed in clear cell renal cell carcinoma.

Leroy X, Aubert S, Zini L, Franquet H, Kervoaze G, Villers A, Delehedde M, Copin M‐C & Lassalle P 
(2010) Histopathology56, 180–187

Contemporary Management of Adrenocortical Carcinoma

CONTEXT Adrenocortical carcinoma (ACC) is a rare and typically aggressive malignancy. Available recommendations are based primarily on retrospective series or expert opinions, and only few prospective clinical studies have yet been published. OBJECTIVE To combine the available evidence for diagnostic work-up and treatment of ACC to a contemporary recommendation on the management of this disease. EVIDENCE ACQUISITION We conducted a systematic literature search for studies conducted on humans and published in English using the Medline/PubMed database up to 31 January 2011. In addition, we screened published abstracts at meetings and several Web sites for recommendations on ACC management. EVIDENCE SYNTHESIS In patients with suspected localised ACC, a thorough endocrine and imaging work-up is followed by complete (R0) resection of the tumour by an expert surgeon. In experienced hands, laparoscopic adrenalectomy is probably as effective and safe for localised and noninvasive ACC as open surgery. Most clinicians agree that mitotane should be used as adjuvant therapy in the majority of patients, as they have a high risk for recurrence. An international panel has suggested using tumour stage, resection status, and the proliferation marker Ki67 as guidance for or against adjuvant therapy. In patients with advanced disease at presentation or recurrence not amenable to complete resection, a surgical approach is frequently inadequate. In these cases, mitotane alone or in combination with cytotoxic drugs is the treatment of choice. The most promising regimens (etoposide, doxorubicin, cisplatin plus mitotane, and streptozotocin plus mitotane) are currently compared in an international phase 3 trial, and results should be available by the end of 2011. Several targeted therapies are under investigation and may lead to new treatment options. Management of endocrine manifestations with steroidogenesis inhibitors is required in patients suffering uncontrolled hormone excess. CONCLUSIONS Detailed recommendations are provided to guide the management of patients with ACC.

Renal Cell Carcinoma (RCC) in Patients With End-Stage Renal Disease Exhibits Many Favourable Clinical, Pathologic, and Outcome Features Compared With RCC in the General Population

BACKGROUND Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.

Conditional Survival Predictions After Nephrectomy for Renal Cell Carcinoma

PURPOSE Conditional survival implies that on average long-term cancer survivors have a better prognosis than do newly diagnosed individuals. We explored the effect of conditional survival in renal cell carcinoma. MATERIALS AND METHODS We studied 3,560 patients with renal cell carcinoma of all stages treated with nephrectomy. We applied conditional survival methodology to a previously reported posttreatment nomogram predicting survival after nephrectomy for patients with renal cell carcinoma stage I to IV. We used the same predictor variables that were integrated in the original multivariable Cox regression models, namely TNM stage, Fuhrman grade, tumor size and symptom classification. To validate the conditional survival nomogram we used an independent cohort of 3,560 patients from 15 institutions. RESULTS The 5-year survival of patients immediately after nephrectomy was 74.2%, which increased to 80.4%, 85.1%, 90.6% and 89.6% at 1, 2, 5 and 10 years after nephrectomy, respectively. The predicted probabilities varied by as much as 50% when, for example, predictions of renal cell carcinoma specific mortality at 10 years were made after nephrectomy vs 5 years later. Within the external validation cohort the accuracy of the conditional nomogram was 89.5%, 90.5%, 88.5% and 86.7% at 1, 2, 5 and 10 years after nephrectomy. CONCLUSIONS We developed (2,530) and externally validated (3,560) a conditional nomogram for predicting renal cell carcinoma specific mortality that allows consideration of the length of survivorship. Our tool provides the most realistic prognosis estimates with high accuracy.

Renal cell carcinoma with rhabdoid features: an aggressive neoplasm with overexpression of p53.

CONTEXT Adult renal cell carcinoma (RCC) with rhabdoid features is a recently recognized morphologic variant of kidney carcinoma. To date, only very few studies have been published on this subject and p53 was not previously studied. OBJECTIVE To evaluate clinical attributes, morphology, and immunohistochemistry in RCC with rhabdoid component. DESIGN Reviewing a consecutive series of 310 RCCs, we identified 14 cases of RCC with rhabdoid features. All cases were reviewed and subjected to detailed clinical and pathologic studies with immunohistochemical evaluation of p53. RESULTS All tumors were clear RCCs with rhabdoid component representing from 5% to 50% of the tumor volume. Rhabdoid cells were large with a central eosinophilic intracytoplasmic inclusion and an eccentric atypical nucleus. Tumor necrosis was common (13/14) and sometimes extensive. Nine of 14 tumors were staged pT3, 4 of 14 were pT2, and only 1 tumor was pT1. On immunohistochemistry, rhabdoid cells were positive for vimentin (14/ 14), epithelial membrane antigen (11/14), and cytokeratin (9/14). Desmin and smooth muscle actin were always negative. p53 was positive in 10 of 14 tumors in the rhabdoid areas (5%-50% of tumor cells stained) but only in 5 of 14 cases in usual clear renal cell areas. In the follow-up, 10 of 14 patients developed metastases and 6 of 14 died of the disease. The median of survival was 8 months. CONCLUSIONS We showed that RCC with rhabdoid features is a very aggressive neoplasm with a poor prognosis. We observed an overexpression of p53 in the rhabdoid component that may be implicated in the tumor dedifferentiation.

Endoluminal occlusion of the inferior vena cava in renal cell carcinoma with retro- or suprahepatic caval thrombus

To evaluate endoluminal occlusion of the inferior vena cava (IVC) during surgical treatment of renal cell carcinoma (RCC) with either retrohepatic (level II) or suprahepatic (level III) caval tumour thrombus.

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.

A Simple and Accurate Model for Prediction of Cancer-Specific Mortality in Patients Treated with Surgery for Primary Penile Squamous Cell Carcinoma

Purpose: Cancer-specific mortality (CSM) of patients with primary penile squamous cell carcinoma (PPSCC) may be quite variable. Recently, a nomogram was developed to provide standardized and individualized mortality predictions. Unfortunately, it relies on a large number (n = 8) of specific variables that are unavailable in routine clinical practice. We attempted to develop a simpler prediction rule with at least equal accuracy in predicting CSM after surgical removal of PPSCC. Experimental Design: The predictive rule was developed on a cohort of 856 patients identified in the 1988 to 2004 Surveillance, Epidemiology and End Results (SEER) database. The predictors consisted of age, race, SEER stage (localized versus regional versus metastatic), tumor grade, type of surgery (excisional biopsy, partial penectomy, and radical penectomy), and of lymph node status (pN0 versus pN1-3 versus pNx). A look-up table based on Cox regression model-derived coefficients was used for prediction of 5-year CSM. The predictive rule accuracy was tested using the Harrells modification of the area under the receiver operating characteristics curve. Results: SEER stage and histologic grade achieved independent predictor status and qualified for inclusion in the model. The model achieved 73.8% accuracy for prediction of CSM at 5 years after surgery. Both predictors achieved independent predictor status in competing risk regression models addressing CSM, where other cause mortality was controlled for. Conclusion: Despite equivalent accuracy, our predictive rule predicting 5-year CSM in patients with PPSCC is substantially less complex (2 versus 8 variables) than the previously published model.