Preoperative Nomogram Predicting 12-Year Probability of Metastatic Renal Cancer - Evaluation in a Contemporary Cohort - Beyond the Abstract

Preoperative predictive tools may be useful in risk stratification of cancer patients and may assist in treatment decision making. In renal cell carcinoma, several preoperative predictors were developed based on clinical and imaging characteristics prior to nephrectomy. These predictive tools may identify patients which are at high risk for adverse pathologic and oncologic outcomes and suitable for inclusion in neoadjuvant trials,1 or low risk for adverse outcomes which may be more suited for active surveillance instead of surgical treatment.2

Current preoperative predictors were developed based on old patient cohorts. In recent years, there has been a change in the characteristics of renal tumors at the time of diagnosis; today, renal tumors are often identified incidentally and usually at a smaller size and earlier stage.3,4 Thus, additional studies are required to assess whether these nomograms can truly predict adverse outcomes in contemporary cohorts.

In the current study, we used the Raj et al. nomogram, a preoperative nomogram published in 2008 which includes gender, mode of presentation, evidence of lymphadenopathy, evidence of necrosis, and tumor size in order to predict the 12-year metastatic probability.5 The cohort used for building the model included patients treated between the years 1970 - 2004. In addition, the nomogram has not been validated in the past. The aim of our study was to validate the nomogram and evaluate the discrimination and calibration abilities of this nomogram on a contemporary cohort of patients treated at our center between the years 2005 – 2011.

Our current cohort included 1,760 patients. Consistent with the changes described in other cohorts of renal cell carcinoma over the years, when compared to the initial publication of the nomogram, tumors were more often detected incidentally (84% vs. 51%), at a smaller size (median tumor size 3.7 cm vs. 5.3 cm) and with lower rates of lymphadenopathy (2% vs. 6%).  Interestingly, the rate of necrosis was higher in the current cohort (55% vs. 8%). Since tumor necrosis is considered a sign of aggressive disease and adverse outcome,6 the smaller tumors identified in the current cohort should have had a lower rather than higher rate of necrosis. This unexpected difference in the percent of necrosis is likely the results of how necrosis was estimated in both studies. While in the current study, images were re-reviewed and any sign of necrosis was accounted as positive for necrosis, in the previous study only tumors with substantial necrosis were considered positive for the presence of necrosis on imaging. Consistent with the favorable characteristics of the tumors in the current cohort, the 12-year metastatic-free probability rate was 88% compared to 70% in the previous publication.

Despite these differences in patient characteristics, in our current cohort, all the components of the nomogram aside from gender were significantly associated with the appearance of metastases during follow-up when evaluated separately using univariable cox regression analyses. The nomogram showed good discrimination (concordance probability estimate: 0.77 +/- 0.01). Calibration was fair, and the predicted mean survival was consistently lower than the actual survival.

In conclusion, our findings demonstrate the different characteristics of the current cohort compared to the previous cohort used for building the nomogram.  Despite these differences, the nomogram is useful and relevant with good discrimination. We believe that this nomogram, and other similar predictive tools, may be used on contemporary cohorts when considering which patients are at higher risk for adverse pathology and outcomes and therefore suitable for inclusion in neoadjuvant trials. With the advent of genetic markers and accurate renal biopsies, future studies should consider incorporating these markers, which may be obtained from the biopsy specimens, with the aim of improving patient risk stratification.2

Written by: Roy Mano, MD,1,2 and A. Ari Hakimi, MD1

  1. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
  2. Department of Urology, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel

  1. Ghali, Fady, Sunil H. Patel, and Ithaar H. Derweesh. "Current status of immunotherapy for localized and locally advanced renal cell carcinoma." Journal of oncology 2019 (2019).
  2. Sanchez, Alejandro, Adam S. Feldman, and A. Ari Hakimi. "Current management of small renal masses, including patient selection, renal tumor biopsy, active surveillance, and thermal ablation." Journal of Clinical Oncology 36, no. 36 (2018): 3591.
  3. Cooperberg, Matthew R., Katherine Mallin, Jamie Ritchey, Jacqueline D. Villalta, Peter R. Carroll, and Christopher J. Kane. "Decreasing size at diagnosis of stage 1 renal cell carcinoma: analysis from the National Cancer Data Base, 1993 to 2004." The Journal of urology 179, no. 6 (2008): 2131-2135.
  4. Thorstenson, Andreas, Martin Bergman, Ann-Helén Scherman-Plogell, Soheila Hosseinnia, Börje Ljungberg, Jan Adolfsson, and Sven Lundstam. "Tumour characteristics and surgical treatment of renal cell carcinoma in Sweden 2005–2010: a population-based study from the national Swedish kidney cancer register." Scandinavian journal of urology 48, no. 3 (2014): 231-238.
  5. Raj, Ganesh V., R. Houston Thompson, Bradley C. Leibovich, Michael L. Blute, Paul Russo, and Michael W. Kattan. "Preoperative nomogram predicting 12-year probability of metastatic renal cancer." The Journal of urology 179, no. 6 (2008): 2146-2151.
  6. Zhang, Lijin, Zhenlei Zha, Wei Qu, Hu Zhao, Jun Yuan, Yejun Feng, and Bin Wu. "Tumor necrosis as a prognostic variable for the clinical outcome in patients with renal cell carcinoma: a systematic review and meta-analysis." BMC cancer 18, no. 1 (2018): 1-13.
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