Luca Cindolo

Multi-Institutional Validation of a New Renal Cancer–Specific Survival Nomogram

PURPOSE We tested the hypothesis that the prediction of renal cancer-specific survival can be improved if traditional predictor variables are used within a prognostic nomogram. PATIENTS AND METHODS Two cohorts of patients treated with either radical or partial nephrectomy for renal cortical tumors were used: one (n = 2,530) for nomogram development and for internal validation (200 bootstrap resamples), and a second (n = 1,422) for external validation. Cox proportional hazards regression analyses modeled the 2002 TNM stages, tumor size, Fuhrman grade, histologic subtype, local symptoms, age, and sex. The accuracy of the nomogram was compared with an established staging scheme. RESULTS Cancer-specific mortality was observed in 598 (23.6%) patients, whereas 200 (7.9%) died as a result of other causes. Follow-up ranged from 0.1 to 286 months (median, 38.8 months). External validation of the nomogram at 1, 2, 5, and 10 years after nephrectomy revealed predictive accuracy of 87.8%, 89.2%, 86.7%, and 88.8%, respectively. Conversely, the alternative staging scheme predicting at 2 and 5 years was less accurate, as evidenced by 86.1% (P = .006) and 83.9% (P = .02) estimates. CONCLUSION The new nomogram is more contemporary, provides predictions that reach further in time and, compared with its alternative, which predicts at 2 and 5 years, generates 3.1% and 2.8% more accurate predictions, respectively.

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSE To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. RESULTS The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. CONCLUSION This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

Laparoendoscopic Single-site Surgery in Urology: Worldwide Multi-institutional Analysis of 1076 Cases

BACKGROUND Laparoendoscopic single-site surgery (LESS) has gained popularity in urology over the last few years. OBJECTIVE To report a large multi-institutional worldwide series of LESS in urology. DESIGN, SETTING, AND PARTICIPANTS Consecutive cases of LESS done between August 2007 and November 2010 at 18 participating institutions were included in this retrospective analysis. INTERVENTION Each group performed a variety of LESS procedures according to its own protocols, entry criteria, and techniques. MEASUREMENTS Demographic data, main perioperative outcome parameters, and information related to the surgical technique were gathered and analyzed. Conversions to reduced-port laparoscopy, conventional laparoscopy, or open surgery were evaluated, as were intraoperative and postoperative complications. RESULTS AND LIMITATIONS Overall, 1076 patients were included in the analysis. The most common procedures were extirpative or ablative operations in the upper urinary tract. The da Vinci robot was used to operate on 143 patients (13%). A single-port technique was most commonly used and the umbilicus represented the most common access site. Overall, operative time was 160±93 min and estimated blood loss was 148±234 ml. Skin incision length at closure was 3.5±1.5 cm. Mean hospital stay was 3.6±2.7 d with a visual analog pain score at discharge of 1.5±1.4. An additional port was used in 23% of cases. The overall conversion rate was 20.8%; 15.8% of patients were converted to reduced-port laparoscopy, 4% to conventional laparoscopy/robotic surgery, and 1% to open surgery. The intraoperative complication rate was 3.3%. Postoperative complications, mostly low grade, were encountered in 9.5% of cases. CONCLUSIONS This study provides a global view of the evolution of LESS in the field of minimally invasive urologic surgery. A broad range of procedures have been effectively performed, primarily in the academic setting, within diverse health care systems around the world. Since LESS is performed by experienced laparoscopic surgeons, the risk of complications remains low when stringent patient-selection criteria are applied.

Prognostic Value of Renal Vein and Inferior Vena Cava Involvement in Renal Cell Carcinoma

BACKGROUND The prognostic significance of venous tumor thrombus extension in patients with renal cell carcinoma (RCC) is a matter of many controversies in the current literature. OBJECTIVE To evaluate the prognostic role of inferior vena cava (IVC) involvement in a large series of pT3b and pT3c RCCs. DESIGN, SETTING, AND PARTICIPANTS A total of 1192 patients from 13 European institutions underwent a radical nephrectomy for pT3b and pT3c RCC between 1982 and 2003. The patients were evaluated in a retrospective manner. Age, gender, clinical symptoms, Eastern Cooperative Oncology Group (ECOG) performance status, TNM stage, tumor size, adrenal invasion, perinephric fat invasion, histological type, and Fuhrman grade were reviewed. The log-rank and Cox uni- and multivariate regression analyses were used to evaluate prognostic factors for overall survival. MEASUREMENTS Overall survival and prognostic factors for overall survival in patients with RCC extending to the renal vein (RV) or to the IVC. RESULTS AND LIMITATIONS The median follow-up was 61.4 mo (56.3-66.5 mo). The mean age was 63.2 yr. The mean tumor size was 8.9 cm. Group 1 (Gr 1) included 933 patients with a renal vein tumor thrombus (78.3%), Group 2 (Gr 2) included 196 patients with a subdiaphragmatic IVC tumor thrombus (16.4%), and Group 3 (Gr 3) included 63 patients with a supradiaphragmatic IVC tumor thrombus (5.3%). Median survival was 52 mo for Gr 1, 25.8 mo for Gr 2, and 18 mo for Gr 3. In univariate analysis, Gr 1 had a significantly better overall survival than Gr 2 (p<0.001) and Gr 3 (p<or=0.001). No significant difference in survival was noted between Gr 2 and Gr 3 (p=0.613). Prognostic factors for overall survival in univariate analysis were clinical symptoms (p<0.001), tumor size (p<0.001), perinephric fat invasion (p<0.001), Fuhrman grade (p<0.001), histological type (p=0.021), lymph node invasion (p<0.001), and distant metastasis (p<0.001). Independent prognostic factors in multivariate analysis were tumor size (p=0.013), perinephric fat invasion (p=0.003), lymph node invasion (p<0.001), distant metastasis (p<0.001), and IVC invasion (p=0.008). CONCLUSIONS The level of tumor thrombus in the IVC does not significantly affect long-term overall survival in patients with renal cell carcinoma. The overall survival was statistically different for patients with a tumor thrombus in the RV compared to those with IVC involvement. This has to be considered for the next revision of the TNM system, and the pT3b and pT3c stages have to be redesigned.

Prognostic ability of simplified nuclear grading of renal cell carcinoma.

The Fuhrman grading system is an established predictor of survival in patients with renal cell carcinoma (RCC). The predictive accuracy of various Fuhrman grading schemes was tested with the intent of improving the prediction of RCC‐specific survival (RCC‐SS).

Galectin-1 and galectin-3 expression in human bladder transitional-cell carcinomas

Galectin‐1 and galectin‐3 are galactoside‐binding proteins involved in different steps of tumor progression and potential targets for therapy. We have investigated the expression of these galectins in 38 human bladder transitional‐cell carcinomas of different histological grade and clinical stage and in 5 normal urothelium samples. Galectin‐1 mRNA levels were highly increased in most high‐grade tumors compared with normal bladder or low‐grade tumors. Western blot and immuno‐histochemical analysis of normal and neoplastic tissues revealed a higher content of galectin‐1 in tumors. Galectin‐3 mRNA levels were also increased in most tumors compared with normal urothelium, but levels were comparable among tumors of different histological grade. Int. J. Cancer (Pred. Oncol.) 84:39–43, 1999.

A Preoperative Prognostic Model for Patients Treated with Nephrectomy for Renal Cell Carcinoma

BACKGROUND Currently two pretreatment prognostic models with limited accuracy (65-67%) can be used to predict survival in patients with localized renal cell carcinoma (RCC). OBJECTIVE We set out to develop a more accurate pretreatment model for predicting RCC-specific mortality after nephrectomy for all stages of RCC. DESIGN, SETTING, AND PARTICIPANTS The data originated from a series of prospectively recorded contemporary cases of patients treated with radical or partial nephrectomy between 1984 and 2006. Model development was performed using data from 2474 patients from five centers and external validation was performed using data from 1972 patients from seven centers. MEASUREMENTS The probability of RCC-specific mortality was modeled using Cox regression. The significance of the predictors was confirmed using competing risks analyses, which account for mortality from other causes. RESULTS AND LIMITATIONS Median follow-up in patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the development and validation cohorts, respectively. The freedom from cancer-specific mortality rates in the nomogram development cohort were 75.4% at 5 yr after nephrectomy and 68.3% at 10 yr after nephrectomy. All variables except gender achieved independent predictor status. In the external validation cohort the nomogram predictions were 88.1% accurate at 1 yr, 86.8% accurate at 2 yr, 86.8% accurate at 5 yr, and 84.2% accurate at 10 yr. CONCLUSIONS Our model substantially exceeds the accuracy of the existing pretreatment models. Consequently, the proposed nomogram-based predictions may be used as benchmark data for pretreatment decision making in patients with various stages of RCC.

Atypical presentations and rare metastatic sites of renal cell carcinoma: a review of case reports

Renal cell carcinoma is a potentially lethal cancer with aggressive behavior and a propensity for metastatic spread. Due to the fact that the patterns of metastases from renal cell carcinomas are not clearly defined, there have been several reports of cases of renal cell carcinoma associated with rare metastatic sites and atypical presenting symptoms. The present review focuses on these atypical rare clinical presentations of renal cell carcinomas both at the time of diagnosis of the primary tumor but also in the years after radical nephrectomy.

Partial Versus Radical Nephrectomy in Patients With Adverse Clinical or Pathologic Characteristics

OBJECTIVES To assess cancer-specific survival of partial nephrectomy (PN) patients with >or= 7-cm lesions or unfavorable pathology (stage T3a or Fuhrman grades III-IV). MATERIAL AND METHODS At 13 participation centers, 4072 partial or radical nephrectomies (RN) were performed for RCC between 1984 and 2001. Of all procedures, 925 (22.7%) were for tumors > 7 cm, 973 (23.9%) had Fuhrman grades III or IV, and 861 (21.1%) had stage pT3a. None had nodal or distant metastases. Matched (age, gender, tumor size, T stage, histologic subtype, and Fuhrman grade [FG]) survival analyses addressed the effect of nephrectomy type (partial vs radical) on cancer-specific mortality. RESULTS Partial nephrectomy for tumors > 7 cm was associated with higher mortality than RN (HR = 5.3; P = .025). No significant cancer-specific survival differences were recorded after PN for FG III-IV (HR = 0.7, P = .5) or for pT3a lesions (HR = 2.5, P = .9). CONCLUSIONS Partial nephrectomy may undermine cancer control in patients with tumors > 7 cm. Conversely, after PN, the same cancer control rates as after RN may be expected in patients with Fuhrman grades III-IV or with pT3a histology.

Stage-specific effect of nodal metastases on survival in patients with non-metastatic renal cell carcinoma

To quantify the survival disadvantage related to the presence of exclusive nodal metastases (eNM) in patients with otherwise non‐metastatic (M0) renal cell carcinoma (RCC).