AUA 2022: The Impact Of Primary Tumor Size On Cancer-Specific And All-Cause Mortality In Patients Undergoing Cytoreductive Nephrectomy For Metastatic Renal Cell Carcinoma: Analysis From The International Marker Consortium For Renal Cancer

( In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Nasseri presented results of an analysis examining the effect of primary tumor size on survival for patients undergoing cytoreductive nephrectomy (CN).

The role of cytoreductive nephrectomy is evolving quite rapidly: while this was well established during the cytokine era, the CARMENA trial demonstrated no survival advantage among patients receiving sunitinib as systemic therapy. However, with immune checkpoint inhibitors now forming the backbone of systemic therapy for patients with metastatic renal cell carcinoma, the immunological impact of cytoreduction of the primary tumor on systemic disease has re-emerged. Historically, it was recognized by the phenomenon of spontaneous regression of distant metastases.

To assess the role of tumor size on outcomes for these patients, the authors performed a multicenter, retrospective analysis using the International Marker Consortium for Renal Cancer (INMARC). They identified patients who received CN and systemic therapy from 2001-2019. The primary outcome was cancer-specific mortality (CSM) and the secondary outcome was all-cause mortality (ACM). Kaplan Meier analysis were used to elucidate survival outcomes. The association between demographic and clinical disease factors with survival outcomes was examined using multivariable Cox regression.

The authors identified 360 patients, of whom 259 were male and 101 were female. The mean age at the time of cytoreductive surgery was 61 years. Primary clinical tumor size was ≥7cm in 249/360 (69.2%) of patients.

Over a median follow-up time of 16 months (IQR: 6.4-42.3), 50 (13.9%) patients experienced CSM, while 218 (61%) experienced ACM.


On multivariable Cox regression analysis, primary clinical tumor size ≥7cm (HR 2.55, p=0.027) and hypertension (HR 3.67, p=0.031) were independently associated with worsened CSM, while papillary type RCC was associated with lowered CSM (HR 0.24, p=0.015). Assessing the secondary outcome, primary clinical Tumor size ≥7cm was associated with an increased risk of ACM (HR 1.47, p=0.026) in this patient population.


The authors conclude that this analysis demonstrates that a larger primary tumor (in this case dichotomized at 7cm) in independently associated with increased cause-specific and all-cause mortality among patients with mRCC undergoing cytoreductive nephrectomy. Further investigation is necessary to confirm this observation and to delineate the mechanisms responsible for this phenomenon.

Presented by: Ryan Isaac Nasseri, MD, BS – University of California, San Diego