BACKGROUND: The objective of the current study was to develop an algorithm to predict progression to metastases after radical nephrectomy for patients with clinically localized renal cell carcinoma (RCC) to allow stratification of patients for potential adjuvant therapy trials.METHODS: The authors identified 1671 sporadic patients with clinically localized, unilateral clear cell RCC who underwent radical nephrectomy between 1970 and 2000. The clinical features examined included age, gender, smoking history, recent onset hypertension, performance status, and presenting symptoms. The pathologic features examined included surgical margins, tumor stage, regional lymph node status, tumor size, nuclear grade, histologic tumor necrosis, sarcomatoid component, cystic architecture, and multifocality. Metastases free survival was estimated using the Kaplan–Meier method. A multivariate Cox proportional hazards regression model was fit to determine associations between the clinical and pathologic features and distant metastases.RESULTS: The median follow‐up was 5.4 years (range, 0–31 years). Metastases occurred in 479 patients at a median of 1.3 years (range, 0–25 years) after nephrectomy. The estimated metastases free survival rates were 86.9% at 1 year, 77.8% at 3 years, 74.1% at 5 years, 70.8% at 7 years, and 67.1% at 10 years. Multivariate analysis showed that the following features were associated with progression to metastases: tumor stage, regional lymph node status, tumor size, nuclear grade, and histologic tumor necrosis (P < 0.001 for all).CONCLUSIONS: In patients with clear cell RCC, tumor stage, regional lymph node status, tumor size, nuclear grade, and histologic tumor necrosis showed statistically significant associations with progression to metastatic RCC. The authors present a scoring algorithm based on these features that can be used to predict disease progression after patients undergo radical nephrectomy for clinically localized clear cell RCC. Cancer 2003;97:1663–71. © 2003 American Cancer Society.DOI 10.1002/cncr.11234

We compared outcomes between patients treated with nephron sparing surgery (NSS) without imperative indications for renal preservation and radical nephrectomy (RN) for 4 to 7 cm renal cell carcinoma (RCC). We identified 91 patients treated with NSS and 841 patients treated with RN for 4 to 7 cm RCC between 1970 and 2000. Cancer specific, distant metastases-free and recurrence-free survivals were estimated using the Kaplan-Meier method. Cancer specific survival rates at 5 years for patients treated with NSS and RN for 4 to 7 cm RCC were 98% and 86%, respectively. On univariate analysis patients treated with RN for 4 to 7 cm RCC were more likely to die of RCC compared to patients treated with NSS. However, after adjusting for features associated with death from RCC including stage, grade, histological tumor necrosis and histological subtype, this difference was no longer statistically significant (risk ratio 1.60, 95% CI 0.50–5.12, p = 0.430). Distant metastases-free survival rates at 5 years for patients treated with NSS and RN were 94% and 83%, respectively. On univariate analysis patients treated with RN were more likely to have tumors that metastasized compared to patients treated with NSS, although this difference was no longer significant after adjusting for the features listed previously (risk ratio 1.76, 95% CI 0.64–4.83, p = 0.273). Recurrence-free survival rates at 5 years for patients treated with NSS and RN were 94% and 98%, respectively. On univariate analysis patients treated with RN were less likely to have recurrence compared to patients treated with NSS (risk ratio 0.32, 95% CI 0.12–0.85, p = 0.022). There were no statistically significant differences in cancer specific survival and distant metastases-free survival between patients treated with NSS and RN for 4 to 7 cm RCC after adjusting for important pathological features. NSS for 4 to 7 cm RCC results in excellent outcome in appropriately selected patients.

There are significant differences in clinicopathological features among renal cell carcinoma histological subtypes but controversy exists regarding the independent impact of histological subtype on patient outcome after nephrectomy. We examined the significance of histological subtype on progression to distant metastasis and cancer specific death after nephrectomy. In a retrospective review of our institutional nephrectomy registry we identified 3,062 patients treated surgically for clear cell, papillary or chromophobe renal cell carcinoma between 1970 and 2003. We identified 2,466 patients (80.5%) with clear cell, 438 (14.3%) with papillary and 158 (5.2%) with chromophobe renal cell carcinoma. There were significant differences in age at surgery, gender, symptoms at presentation, tumor size, stage and grade, tumor necrosis, sarcomatoid differentiation and multifocality among the 3 renal cell carcinoma subtypes (p <0.01 for all). A significant difference in metastasis-free and cancer specific survival existed between patients with clear cell renal cell carcinoma and the 2 other subtypes, although no significant difference in these outcomes was identified between patients with the papillary and chromophobe subtypes. The clear cell renal cell carcinoma subtype remained a significant predictor of metastasis (HR 2.76, 95% CI 2.05-3.73) and cancer specific death (HR 1.77, 95% CI 1.38-2.26, each p <0.001) after multivariate adjustment for the features listed above. Histological subtype is an independent predictor of progression to distant metastasis and cancer specific death in patients with renal cell carcinoma.

BACKGROUND: Although a role for resection of solitary metastases from renal cell carcinoma (RCC) has been described, the utility of surgery in patients with multiple sites of disease has been less well defined. The authors report the survival of patients who underwent complete metastasectomy for multiple RCC metastases.METHODS: The authors identified 887 patients who underwent nephrectomy for RCC between 1976 and 2006 who developed multiple metastatic lesions. The impact of complete metastasectomy on survival was evaluated controlling for the timing, location, and number of metastases and for patient performance status.RESULTS: Of 887 patients, 125 (14%) underwent complete surgical resection of all metastases. Complete metastasectomy was associated with a significant prolongation of median cancer‐specific survival (CSS) (4.8 years vs 1.3 years; P < .001). Patients who had lung‐only metastases had a 5‐year CSS rate of 73.6% with complete resection versus 19% without complete resection (P < .001). A survival advantage from complete metastasectomy also was observed among patients with multiple, nonlung‐only metastases, who had a 5‐year CSS rate of 32.5% with complete resection versus 12.4% without complete resection (P < .001). Complete resection remained predictive of improved CSS for patients who had ≥3 metastatic lesions (P < .001) and for patients who had synchronous (P < .001) and asynchronous (P = .002) multiple metastases. Moreover, on multivariate analysis, the absence of complete metastasectomy was associated significantly with an increased risk of death from RCC (hazard ratio, 2.91; 95% confidence interval, 2.17‐3.90; P < .001).CONCLUSIONS: The current results indicated that complete resection of multiple RCC metastases may be associated with long‐term survival and should be considered when technically feasible in appropriate surgical candidates. Cancer 2011. © 2011 American Cancer Society.

We developed a clinically useful scoring algorithm to predict cancer specific survival for patients with clear cell metastatic renal cell carcinoma (RCC). We studied 727 patients treated with radical nephrectomy for clear cell RCC from 1970 to 2000 who had distant metastases at nephrectomy (285) or in whom metastases subsequently developed (442). A scoring algorithm to predict cancer specific survival was developed using the regression coefficients from a Cox proportional hazards model. There were 606 deaths from clear cell RCC at a median of 1.0 years (range 0 to 14) following metastatic RCC. Constitutional symptoms at nephrectomy (+2), metastases to the bone (+2) or liver (+4), metastases in multiple simultaneous sites (+2), metastases at nephrectomy (+1) or within 2 years of nephrectomy (+3), complete resection of all metastatic sites (-5), tumor thrombus level I to IV (+3), and the primary pathological features of nuclear grade 4 (+3) and histological tumor necrosis (+2) were significantly associated with death from RCC. All patients started with a score of 0 and points were added or subtracted as indicated in parentheses. Cancer specific survival rates at 1 year were 85.1%, 72.1%, 58.8%, 39.0%, and 25.1%, respectively, for patients with scores of -5 to -1, scores of 0 to 2, scores of 3 to 6, scores of 7 or 8, and scores of 9 or more. This scoring algorithm can be used to predict cancer specific survival for patients with metastatic clear cell RCC.