Presence of Tumor Necrosis is Not a Significant Predictor of Survival in Clear Cell Renal Cell Carcinoma: Higher Prognostic Accuracy of Extent Based Rather Than Presence/Absence Classification

Klatte, Tobias; Said, Jonathan W.; de Martino, Michela; LaRochelle, Jeffrey; Shuch, Brian; Rao, Jian Yu; Thomas, George V.; Kabbinavar, Fairooz F.; Belldegrun, Arie S.; Pantuck, Allan J.

doi:10.1016/j.juro.2008.11.098

« Previous Next »The Journal of Urology
Volume 181, Issue 4 , Pages 1558-1564, April 2009

Presence of Tumor Necrosis is Not a Significant Predictor of Survival in Clear Cell Renal Cell Carcinoma: Higher Prognostic Accuracy of Extent Based Rather Than Presence/Absence Classification

Tobias Klatte
- Department of Urology, University of California-Los Angeles, Los Angeles, California
Jonathan W. Said
- Department of Pathology and Laboratory Medicine, University of California-Los Angeles, Los Angeles, California
Michela de Martino
- Department of Urology, University of California-Los Angeles, Los Angeles, California
Jeffrey LaRochelle
- Department of Urology, University of California-Los Angeles, Los Angeles, California
Brian Shuch
- Department of Urology, University of California-Los Angeles, Los Angeles, California
Jian Yu Rao
- Department of Pathology and Laboratory Medicine, University of California-Los Angeles, Los Angeles, California
George V. Thomas
- Department of Pathology and Laboratory Medicine, University of California-Los Angeles, Los Angeles, California
Fairooz F. Kabbinavar
- Department of Medicine, University of California-Los Angeles, Los Angeles, California
Arie S. Belldegrun
- Department of Urology, University of California-Los Angeles, Los Angeles, California
Allan J. Pantuck
- Department of Urology, University of California-Los Angeles, Los Angeles, California
- Correspondence: Department of Urology, David Geffen School of Medicine at UCLA, Room B7-298 CHS, Box 951738, Los Angeles, California 90095-1738 (telephone: 310-206-2436; FAX: 310-206-4082)

Received 11 August 2008 published online 23 February 2009.

Purpose

The presence of necrosis has been proposed as an adverse prognostic factor in clear cell renal cell carcinoma. However, classification based on a presence/absence basis ignores its heterogeneity, which may be associated with other important pathological factors and prognosis. We performed the first prospective study of necrosis in clear cell renal cell carcinoma to our knowledge and tested the traditional presence/absence classification vs an alternative extent based classification.

Materials and Methods

We studied the presence and extent of tumor necrosis, pathological features and cancer specific survival of 343 consecutive patients.

Results

Tumor necrosis was present in 227 tumors (66%) and was associated with more advanced tumors. However, the predictive accuracy for cancer specific survival was low (64.6%) and the presence of necrosis was not retained as an independent prognostic factor on multivariate analysis (p = 0.299). There was significant heterogeneity among tumors with necrosis. Increasing extent of necrosis was associated with poorer performance status, higher T, N, M stages and grades, vascular invasion and sarcomatoid features. Extent based classification predicted cancer specific survival better than presence alone (74.5% vs 64.6%) and was retained as an independent prognostic factor on multivariate analysis (p = 0.029). For clinical use a cutoff of 20% was identified for further prognostic subclassification of tumors with necrosis (c-index 71.7%).

Conclusions

Tumor necrosis is an adverse prognostic factor in clear cell renal cell carcinoma but prospective evaluation of necrosis on a presence/absence basis shows that it does not provide independent prognostic information. The predictive accuracy of an extent based classification is superior and is retained as an independent prognostic factor. We recommend the scoring of necrosis according to its extent with further subclassification based on a 20% cutoff.

Key Words: necrosis, carcinoma, renal cell, kidney neoplasms, survival

Abbreviations and Acronyms: ccRCC, clear cell renal cell carcinoma, CSS, cancer specific survival, ECOG PS, Eastern Cooperative Oncology Group performance status, RCC, renal cell carcinoma