Introduction:

Management of metastatic Renal Cell Carcinoma (mRCC) is in the process of a dramatic evolution with the proliferation of systemic agents and reassessment of the role of cytoreductive surgery. The immunological impact of cytoreduction of the primary tumor on systemic disease has long been recognized by the phenomenon of spontaneous regression of distant metastases.  We sought to investigate the impact of commonly considered clinical and histologic features on survival outcomes following cytoreductive nephrectomy (CN) for mRCC.

Methods:

We performed a multicenter, retrospective analysis using the International Marker Consortium for Renal Cancer (INMARC) identified patients who received CN and systemic therapy from 2005-2019. Demographic and clinical disease factors were analyzed using multivariable Cox regression. Primary outcome was cancer-specific mortality (CSM), secondary outcome was all-cause mortality (ACM).

Results:

The cohort consisted of 360 patients, 259 male/101 female. Median follow-up time was 16 months (IQR: 6.4-42.3); 50 (13.9%) patients experienced CSM, while 218 (61%) experienced ACM. Mean age at surgery was 61 years. Primary clinical tumor size was ≥7cm in 249/360 (69.2%) of patients. 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 RCC was associated with lowered CSM (HR 0.24, p=0.015). Primary clinical Tumor size ≥7cm was also associated with an increased risk of ACM (HR 1.47, p=0.026).

Conclusion:

Increased primary clinical tumor size ≥7cm was an independent risk factor associated with worsened CSM and ACM in patients with mRCC.  Further investigation is necessary to confirm our findings and to delineate the mechanisms responsible for this phenomenon.

Funding: Stephen Weissman Kidney Cancer Research Fund