A.J. Pantuck

Ultrasound-based combination therapy: potential in urologic cancer

Immune-sensitive urologic malignancies include prostate, kidney and bladder cancers. To date, most immunotherapeutic treatments have been applied to advanced metastatic disease. Limited efficacy in this setting is likely due to an excessive disease burden, which overwhelms the capacity of the immune system. Immunotherapy has not been widely utilized in a low-disease-burden state – a setting in which the immune system may be best suited to effectively mount a clinically meaningful response. The emergence of high-intensity focused ultrasound, and more recently, low-intensity focused ultrasound technologies, have demonstrated not only immune-stimulatory effects but also an interesting capacity to alter tissue architecture and cell membrane properties, which may be exploited to increase tumoral uptake of drugs and vaccines. In this article, we review the literature supporting the novel use of ultrasound combination therapy with adjunctive agents in the treatment of urologic malignancy.

Comment se comparent néphrectomies partielles et élargies pour le traitement des carcinomes papillaires pT1aN0M0 ? Étude comparative rétrospective de 277 cas

PURPOSE Our objective was to compare oncologic results of nephron sparing surgery (NSS) versus radical nephrectomy (RN) in T1aN0-x M0 papillary renal cell carcinoma (PRCC). PATIENTS AND METHODS We retrospectively reviewed 277 patients treated for a pT1aN0M0 PRCC selected from an academic database from 12 centres. We compared the clinico-pathological features by using Chi-square and Student statistical analyses. Survivals analyses using Kaplan-Meier and Log-rank models were performed. RESULTS The two groups were composed by 186 patients treated by NSS and 91 by RN. The TNM stage was fixed and the two groups were, in terms of age and Fuhrman grade, comparable. Median age at diagnosis was 59 years (27-85). Median tumor size was 2.7 cm (0.4-4). The average follow-up was 49 months (1-246). Very few events arose in both groups: two local recurrences were observed in the NSS group (1.07%), three patients died of cancer in the NSS treated group (1.6%) and five in the RN treated group (5.5%). The five and 10 cancer-specific survival rate were comparable in the two groups (98% vs. 100% and 98% vs. 97%). The specific survival curves were perfectly similar for both groups (log rank test, p=0.25). CONCLUSION NSS is equivalent to RN as far as oncologic control of pT1aN0M0 PRCC is concerned.

156 METACHRONOUS BILATERAL RENAL CELL CARCINOMA: RISK ASSESSMENT, PROGNOSIS AND RELEVANCE OF THE PRIMARY-FREE INTERVAL

PURPOSE We evaluated the prognosis, risk factors and relevance of the primary-free interval in a large cohort with metachronous bilateral renal cell carcinoma. MATERIALS AND METHODS We studied 120 patients with metachronous, bilateral renal cell carcinoma who were treated at 12 international academic centers. Logistic regression was performed to evaluate risk factors for contralateral metachronous renal cell carcinoma during followup. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS Median age at diagnosis of the first and second renal cell carcinomas was 54 and 62 years, respectively. The most common histological subtype was bilateral clear cell renal cell carcinoma (89% of cases). Familial renal cell carcinoma was found in 14% of patients, von Hippel-Lindau disease was found in 4% and nonfamilial renal cell carcinoma was found in 81%. The 15-year disease specific survival rates for the first and second renal cell carcinomas were 66% and 44%, respectively. Logistic regression revealed von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age as independent risk factors for contralateral renal cell carcinoma after surgery for unilateral renal cell carcinoma. A longer primary-free interval was associated with a better prognosis. When calculating disease specific survival from the diagnosis of the first renal cell carcinoma, the primary-free interval was an independent prognostic factor. CONCLUSIONS Long-term survival rates of metachronous, bilateral renal cell carcinoma are moderate. von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age are independent risk factors for contralateral renal cell carcinoma. These risk factors support close and extended abdominal surveillance following nephrectomy for unilateral renal cell carcinoma. Patients with a longer primary-free interval have a more favorable prognosis.

Prognostic Value of Histologic Subtypes in Renal Cell Carcinoma: A Multicenter Experience

PURPOSE To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. RESULTS Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). CONCLUSION The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

MORBIDITY AND CLINICAL OUTCOME OF NEPHRON-SPARING SURGERY IN RELATION TO TUMOUR SIZE AND INDICATION

OBJECTIVE To analyse through a large multicentre series, morbidity of nephron-sparing surgery (NSS) in relation to tumour size and surgical indication. METHODS The study included patients from eight international academic centres. Age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), surgical margins, local and distant recurrences, and overall and cancer-specific survival rates were collected and analysed. Indication for elective or mandatory NSS, medical and surgical complication rates, mean blood loss, blood transfusion, and length of hospital stay were specifically recorded for the purpose of this study. Groups were compared for qualitative and quantitative variables by using chi(2) (Fischer exact test) and Student t tests, respectively. RESULTS A total of 1048 NSS procedures were included in this study. Mean tumour size was 3.4+/-2.1cm. In 730 elective procedures mean operative time (p=0.002), mean blood loss (p=0.01), the need for blood transfusion (p=0.001), and urinary fistula rate (p=0.01) were significantly increased for tumours >4 cm. However, these differences did not result in significantly increased medical (p=0.4), surgical complication rates (p=0.6), or length of hospital stay (p=0.9). Finally, in elective procedures for malignant tumours, positive surgical margins, local or distant recurrence rates, and cancer-specific survival were not significantly different in tumours < or =4 cm and >4 cm. CONCLUSION Excellent cancer control and outcomes can be achieved with NSS in carefully selected patients with tumours >4 cm. Expanding the size indication of elective NSS results in an increased but acceptable morbidity.