2. UroToday Home
  3. Recent Abstracts
  4. Urologic Oncology
  5. Renal Cancer

Node Positive Resected Renal Cell Carcinoma Portends a Poor Prognosis: Results From the Canadian Kidney Cancer Collaboration - Beyond the Abstract

Pathologically node-positive, non-metastatic renal cell carcinoma (pN1M0 RCC), under the current AJCC staging systems, is classified as Stage III, alongside locally advanced node-negative patients. For decades, retrospective data have suggested these patients behave far more like patients with metastatic disease. Part of the challenge in studying this population is the rarity of pN1M0 status and variations in indications for lymph node dissection (LND), likely resulting in many of these patients going undetected. This has left clinicians with limited contemporary data to guide counseling or treatment decisions, particularly in the era of adjuvant immunotherapy.

Our study utilized the Canadian Kidney Cancer Information System (CKCis), a prospective multi-institutional registry spanning 15 centers across 6 Canadian provinces. Among 10,641 patients undergoing radical or partial nephrectomy for non-metastatic RCC, only 1.4% (n = 149) had pN1 disease. Our final analytic cohort of 113 patients with clear cell, papillary, or chromophobe histology (none of whom received adjuvant therapy) represents one of the largest contemporary series of surgically resected pN1M0 RCC.

A striking recurrence rate of 77% (87/113) at a median of 4.8 months following surgery was observed, with 68% (59/87) of recurrences consisting of distant metastatic disease. Survival outcomes further reinforced the aggressive biology of this disease, with a median cancer-specific survival (CSS) of 5.5 years and a median overall survival (OS) of 4.4 years. While these outcomes exceed historical pN1M0 estimates, likely reflecting the benefits of contemporary systemic therapy upon recurrence (72% of patients who recurred received systemic therapy), they remain firmly within the range reported for metastatic RCC. Yu et al.1 demonstrated that pN1M0 patients had a median OS of 2.4 years, statistically indistinguishable from patients with de novo metastatic disease, whereas pT3N0M0 patients had a median overall survival of 10.2 years. A contemporary CKCis database study reported a median OS of 36 months for metastatic RCC patients treated with targeted therapy and 72 months for those treated with ICI-based regimens.2 These data reinforce the argument that pN1M0 disease behaves biologically more akin to metastatic RCC than locally advanced node-negative disease, and that its current classification as Stage III may underestimates its true aggressive biology.



KEYNOTE-564 established adjuvant pembrolizumab as a treatment option for patients at increased risk of recurrence after nephrectomy, including pN1M0 RCC, with adjuvant therapy permitted up to 3 months post-surgery.3 In our cohort, 31% (95% CI 23–41%) of patients had already recurred within 3 months of surgery, demonstrating a substantial proportion of pN1 patients develop detectable metastatic disease during the interval between surgery and adjuvant immunotherapy initiation. Although our study was not designed to answer this question, the data raise the hypothesis of whether this subset of patients who recur early are inadequately treated with single-agent adjuvant immunotherapy when they may already harbor overt metastatic disease- a question requiring further exploration in prospective trials. Either way, our data demonstrates that staging imaging prior to adjuvant therapy initiation is essential in pN1M0 patients.

Written by: Jesse TR Spooner, MD, and Senior Author Ricardo Rendon, MD

  • Department of Urology, Dalhousie University, Nova Scotia, Canada.
References:

  1. Yu KJ, Keskin SK, Meissner MA, et al. Renal cell carcinoma and pathologic nodal disease: implications for American Joint Committee on cancer staging. Cancer. 2018;124(20):4023–4031. doi:10.1002/cncr.31661
  2. Sawaya GBN, Dragomir A, Wood LA, et al. Real-world assessment of clinical outcomes in patients with metastatic renal cell carcinoma with or without sarcomatoid features treated with first-line systemic therapies. Eur Urol Oncol. 2024;7(3):570–580. doi:10.1016/j.euo.2023.11.016.
  3. Choueiri TK, Tomczak P, Park SH, et al. Overall survival with adjuvant pembrolizumab in renal-cell carcinoma. N Engl J Med. 2024;390(15):1359–1371. doi:10.1056/NEJMoa2312695.
Read the Abstract