Head-to-head comparison of the most relevant integrated prognostic systems predicting cancer-specific survival in clear cell renal cell carcinoma
Ficarra V.1, Sun M.2, Karakiewicz P.I.2, Novara G.1, Antonelli A.3, Bertini R.4, Carini M.5, Carmignani G.6, Longo N.7, Martignoni G.8, Martorana G.9, Minervini A.5, Mirone V.7, Artibani W.8, Zattoni F.1, Simionato A.6, Siracusano S.10, Terrone C.11 1 University of Padua, Dept. of Urology, Padua, Italy, 2University of Montreal, Dept. of Urology, Montreal, Canada, 3University of Brescia, Dept. of Urology, Brescia, Italy, 4 Vita-Salute University San Raffaele, Dept. of Urology, Milan, Italy, 5University of Florence, Dept. of Urology, Florence, Italy, 6University of Genova, Dept. of Urology, Genova, Italy, 7University Federico II, Dept. of Urology, Naples, Italy, 8University of Verona, Dept. of Urology, Verona, Italy, 9University of Bologna, Dept. of Urology, Bologna, Italy, 10University of Trieste, Dept. of Urology, Trieste, Italy, 11University of Eastern Piedmont, Dept. of Urology, Novara, Italy
Results: All the variables included in the nomograms (age, gender, mode of presentation, clinical tumor size, clinical T stage, presence of metastasis) were independent predictor of CSS in multivariable analysis (all p values <0.02). The prognostic accuracy of the nomogram was 87.8% (IC95% 84.4-91.4) at 12-mo; 87% (IC95% 84.4-89.5) at 24-mo; 84% (IC95% 82.3-87.1) at 60-mo; and 85.9% (IC95% 83.2-88.6) at 120-mo from surgery. Calibrations curve showed that the nomogram tended to significantly overestimate the rates of freedom from cancerspecific mortality a 60 and 120-mo, whereas the differences between estimates and observed rates at 12- and 24-mo were limited. Conclusions: Karakiewicz nomograms has a high prognostic accuracy both in short and long term evaluation of cancer-related outcome of patients with RCC. However, according to our series, the nomograms tend to underestimate the risk of cancer-specific deaths both 60 and 120-mo after surgery.
External validation of the most accurate nomogram cancer specific mortality in renal cell carcinoma
Capitanio U.1, Matloob R.1, Roscigno M.2, Strada E.1, Petralia G.1, Sozzi F.1, Angiolilli D.1, Di Trapani E.1, Carenzi C.1, Karakiewicz P.I.3, Bertini R.1 1 Urological Research Institute, Vita-Salute San Raffaele University, Dept. of Urology, Milan, Italy, 2Hospital Riuniti, Dept. of Urology, Bergamo, Italy, 3CHUM, Dept. of Urology, Montreal, Canada Introduction & Objectives: Accurate prediction of cancer-specific survival in patients with renal cortical tumors (RCs) is important for counselling, planning of follow-up, and selection for appropriate adjuvant trial designs. We aimed to externally validate the most accurate nomogram available (J Clin Oncol 2007, 25(11):1316-22) to predict cancer specific mortality (CSM) in RCC patients. Materials & Methods: Clinical and pathologic data were prospectively gathered in 1170 consecutive patients treated with radical nephrectomy or partial nephrectomy at a single Academic Center, between 1991 and 2010. Nomogram predicted survival probability and actual CSM were compared. Discrimination was quantified with the area under the receiver operating characteristics curve (AUC). Calibration compared the predicted and the observed cancer rates throughout the entire range of predictions. Results: At a median 89-month follow-up 256 renal cell carcinoma related deaths had occurred (21.9%). T classification according to TNM 2010 was pT1a, pT1b, pT2a, pT2b, pT3a, pT3b, pT3c and pT4 in 370 (31.6%), 347 (29.7%), 80 (6.8%), 44 (3.8%), 234 (20.0%), 14 (1.2%), 49 (4.2%) and 32 (2.7%), respectively. Mean pathological diameter of the tumor was 6.1 cm (median 5.0 cm, range 1-23). At nephrectomy lymph node and distant metastases were present in 83 (7.1%) and 182 cases (15.6%), respectively. Grade 1-2 or 3-4 was noted in 824 tumors (70.4%) and 346 (29.5%), respectively. Thirty-seven (3.2%) and 80 (6.8%) patients showed local and systemic symptoms at diagnosis, respectively. One, 2, 5 and 10-year cancer specific survival rates were 91.9%, 87.2%, 79.3% and 72.9%, respectively. For nomogram-derived CSM-free survival predictions at 1 to 10 years, the accuracy of the nomogram ranged from 85.5 to 91.1%. The calibration between the predicted and observed recurrence-free survival rates was virtually perfect at 1 to 5 years after nephrectomy with slightly departures between the predicted and observed rates between 5 and 10 years after nephrectomy. Conclusions: We externally validated a highly accurate tool specifically for renal renal cell carcinoma to predict disease specific survival. This nomogram resulted the most accurate tool to identify renal cell carcinoma with aggressive clinical behavior and may contribute to the ability to individualize postoperative surveillance and therapy.
Introduction & Objectives: To compare the performances of UISS, SSIGN score, and Karakiewicz nomogram in a large multi-institutional series of patients with clear cell RCC. Materials & Methods: We collected retrospectively the preoperative, pathological and follow-up data of 1871 patients treated in 16 academic centers. The predictive accuracy of the three prognostic models for prediction of CSS was quantified according to Harrell’s concordance index, whereas differences were estimated using the DeLong test. Decision curve analyses were used to determine the optimal benefit derived from the use of the 3 models. Results: At a median follow-up of 40 months, 272 (15%) had died of disease. Overall 3- and 5-year CSS estimates were 87.5% and 83.1%, respectively. The predictive accuracy estimates for prediction of CSS at 3 and 5 years were 88.9% and 88.8% for the Karakiewicz nomogram; 85.0%, and 84.1% for the UISS; and 87.9% and 82.5% for the SSIGN score, respectively. Most of the differences in predictive accuracy were statistically significant. Calibration plots demonstrated substantial departures from ideal predictions for all the model. The Karakiewicz nomogram demonstrated the highest net benefit up to threshold probability of 25% and 37% at 3 and 5 yrs, respectively. Following those thresholds, the UISS resulted with the highest net benefits. Conclusions: All three models demonstrated substantially sensible predictive accuracy, but all tend to underestimate the CSS probabilities. The Karakiewicz nomogram demonstrated the highest net benefit up to threshold probabilities of 25% at 3 yr and 37% at 5 yr, whereas, the UISS resulted with the highest net benefit in patients with higher risks of deaths.
Stage-per-stage analysis of age and cancerspecific mortality (CSM) in patients with renal cell carcinoma (RCC): A retrospective analysis
Sun M.1, Lughezzani G.2, Isbarn H.3, Liberman D.1, Ismail S.4, Perrotte P.4 1 University of Montreal Health Center, Cancer Prognostics and Health Outcomes Unit, Montreal, Canada, 2Vita Salute San Raffaele University, Dept. of Urology, Milan, Italy, 3Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany, 4University of Montreal Health Center, Dept. of Urology, Montreal, Canada Introduction & Objectives: Controversy exists in the management of elderly patients with RCC. Some reports suggest that in these patients, surgical treatment may actually cause harm, while others disagree. We sought to test this hypothesis in a large population-based North American cohort. Materials & Methods: Between years 1988 and 2006, 36333 RCC patients treated with partial or radical nephrectomy (RN) were identified within the Surveillance, epidemiology and end results database. Patient age was stratified into decades: <50 vs. 50–59 vs. 60–69 vs. 70–79 vs. ≥80 years old. Disease stage was defined according to the AJCC/TNM staging system: stage I vs. stage II vs. stage III vs. stage IV. Tumor grade was defined low (I–II) vs. high (III–IV). Cox regression analyses were performed for prediction of CSM in the entire population, then repeated according to AJCC stage and grade categories. Finally, we repeated our analyses in patients treated with exclusively RN. Results: Respectively 18, 25, 27, 23, and 7% of patients were aged <50, 50–59, 60–69, 70–79, and ≥80 years. Most patients were white (82%), underwent a RN (80%), clear cell (89%), low grade (74%), and stage I (67%). After adjusting to all covariates, persons aged ≥80 years had a higher rate of CSM than their younger counterparts (hazard ratio [HR]: 2.3, P<0.001). This effect was consistent in the stage per stage analysis: stage I HR: 5.1, P<0.001 vs. stage II HR: 2.0, P<0.001, stage III HR: 1.8, P<0.001, stage IV HR: 1.7, P<0.001. Following stratification of patients according to stage and grade categories, the effect of worse survival in octogenarians persisted across all categories. Furthermore, this finding remained unchanged in patients treated with exclusively RN. Conclusions: More advanced age is an independent predictor of higher CSM across all stage and grade categories after nephrectomy. In consequence, surgical management of the elderly in RCC patients may not represent the ideal treatment option. Further studies are needed to confirm these results.
Eur Urol Suppl 2011;10(2):169