Impact of pathologic lymph node‐positive renal cell carcinoma on survival in patients without metastasis: Evidence in support of expanding the definition of stage IV kidney cancer

Abstract

Background Stage III renal cell carcinoma (RCC) encompasses both lymph node‐positive (pT1‐3N1M0) and lymph node–negative (pT3N0M0) disease. However, prior institutional studies have indicated that among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease. The objective of the current study was to validate these findings using a large, nationally representative sample of patients with kidney cancer. Methods Patients with AJCC stage III or stage IV RCC were identified using the National Cancer Data Base (NCDB). Patients were categorized as having lymph node‐positive stage III (pT1‐3N1M0), lymph node–negative stage III (pT3N0M0), or stage IV metastatic (pT1‐3 N0M1) disease. Cox proportional hazards models compared outcomes while adjusting for comorbidities. Kaplan‐Meier estimates illustrated relative survival when comparing staging groups. Results A total of 8988 patients met the inclusion criteria, with 6587 patients classified as having lymph node–negative stage III disease, 2218 as having lymph node‐positive stage III disease, and 183 as having stage IV disease. Superior survival was noted among patients with lymph node–negative stage III disease, but similar survival was noted between patients with lymph node‐positive stage III and stage IV RCC, with 5‐year survival rates of 61.9% (95% confidence interval [95% CI], 60.3%‐63.4%), 22.7% (95% CI, 20.6%‐24.9%), and 15.6% (95% CI, 11.1%‐23.8%), respectively. Conclusions Current RCC staging systems group pT1‐3N1M0 and pT3N0M0 disease as stage III disease. However, the results of the current validation study suggest the need for further stratification and even placement of patients with pT1‐3N1M0 disease into the stage IV category. Staging that accurately reflects oncologic prognosis may help clinicians better counsel and select patients who might derive the most benefit from lymphadenectomy, adjuvant systemic therapy, more rigorous imaging surveillance, and clinical trial participation.

Delaying surgery for clinical T1b-T2bN0M0 renal cell carcinoma: Oncologic implications in the COVID-19 era and beyond

“…The NCDB, a national oncology registry, records approximately 70% of the incident cancer cases in the United States. It contains information regarding patient demographics, neoplasm staging (both clinical and pathologic staging), surgical treatment, and survival outcomes [12] , [13] , [14] .…”

Renal cell carcinoma with isolated lymph node metastases should be reclassified as stage IV

“…However, the risk of progression is distinctly different for LA/M0 and LN+/M0 tumors, and this should be considered in trial analyses. Using population‐level data, Srivastava et al 7 provide compelling evidence and validate institutional studies demonstrating the different clinical phenotypes for LA/M0 tumors versus LN+/M0 tumors. It is critical that future editions of the American Joint Committee on Cancer staging system recognize the increased risk with LN+/M0 tumors and consider reclassification of LN+/M0 tumors as stage IV tumors so that baseline risks are more accurately measured in these rare populations.…”

“…However, the results of this study are difficult to interpret because only 4% of the patients had lymph node metastases. Although slightly less than one‐third of patients in EORTC 30881 had ≥pT 3 tumors, the incidence of positive lymph nodes was more than 10‐fold less than that for pT 3 tumors in the study by Srivastava et al 7 The current guidelines recommend that surgeons may remove radiographically or grossly involved retroperitoneal lymph nodes, primarily for staging purposes, 10,11 but there is no consensus on LND for RCC with lymph nodes that are not enlarged. Blute et al 12 identified sarcomatoid dedifferentiation, a primary tumor size >10 cm, pT 3 to pT 4 tumors, tumor necrosis, and tumor grade 3 to 4 to be associated with pathologic nodal involvement.…”

“…In the current issue of Cancer , using population‐level data from the National Cancer Database, Srivastava et al 7 provide additional evidence that LN+/M0 RCC should be reclassified as stage IV disease. The authors included stage III and IV patients who had previously undergone nephrectomy with LND.…”

“…Clinically enlarged lymph nodes (≥1 cm) are not uncommon in patients with RCC with large tumors, but less than half of patients with clinically positive nodes have pathologic node involvement 8 . Srivastava et al 7 found that approximately half of their cohort of 41,821 patients with RCC treated with nephrectomy had a diagnostic benefit from LND insofar as their diagnosis of pathologic lymph node metastasis demonstrated an increased risk for poor outcomes. In addition, a diagnosis of lymph node metastasis allows clinicians to potentially select LN+/M0 patients for more aggressive surveillance or enrollment in adjuvant therapy clinical trials.…”