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AUA 2023

AUA 2023: The Role of Cytoreductive Partial Nephrectomy

(UroToday.com) Dr. Ithaar Derweesh presents the role of cytoreductive partial nephrectomy in the setting of metastatic renal cell carcinoma. He does this through the context of a case presentation. A 65F presents with abdominal pain to the ER on 12/2019. PMH is significant for well-controlled HIV, bilateral segmental PE, and CKD Stage III. Her ECOG performance status is 2. CT scan is notable for a 3x4 cm interpolar mass with Level III thrombus and multiple pulmonary nodules. Percutaneous renal tumor biopsy confirms clear cell RCC.


First, he presents a paper by Capitanio et al.1 that addresses this question in the cytokine era (1988-2004). In this SEER study, they compared 46 partial nephrectomies (PN) vs. 1997 radical nephrectomies (RN) and found no significant difference in cancer-specific survival (CSS). This held true in unmatched and matched analysis.

Next, he focused on the targeted therapy era. In a study by Silberstein et al.,2 a pilot study evaluating the efficacy of neoadjuvant targeted therapy prior to cytoreductive PN in patients with an imperative indication for nephron-sparing, 12 patients (14 renal units) underwent neoadjuvant sunitinib. 5 patients had partial response on RECIST criteria. 21% reduction in tumor size noted. 14/14 PN was successful with no positive surgical margins. 3/14 (21%) had a urine leak – but otherwise no significant complications. In a systematic review by Shemshaki et al.,3 they compared outcomes from 542 cytoreductive PN vs. 2127 cytoreductive RN over 4 articles and found comparable CSS results at 1 year, 2 year, and 3 years. No significant difference in overall survival (OS) was noted. Lenis et al.4 utilized the NCDB to also evaluated CPN in the targeted therapy era (2006-2013). They looked at 10,144 patients, of which 381 (3.8%) underwent CPN. Rates of CPN increased from 1.3 to 4.3% during the study period. But on matched analysis, CPN was associated with improved OS compared with CRN, specifically for primary tumors < 4 cm. Similar results were found on propensity score adjusted multivariable analysis.

In terms of current status, there are 11 published series on CPN. No dedicated series in the immunotherapy era though. Data from prior eras suggest

  • CPN does not compromise outcomes in mRCC
  • May be associated with benefits in tumors < 4 cm

Considering that more advanced tumors are at higher risk of functional decline (19% of T1 tumors vs. 35% of T3/T4 tumors at risk of CKD),5 it makes sense to try and preserve renal function when you can.

Gaps in the literature:

  • None of the series of cytoreductive nephrectomies report functional outcome
  • While we may infer benefit of CPN is similar to patients in the localized setting, knowing that higher stage disease is associated with pre-existing functional decline and more profound decline poses a challenge in the “modern era” of IO and IO/TKI combinations, with more effective agents and longer survival –
  • Should we be more concerned about longer term functional decline?

In the case of our patient, she underwent CPN, her final pathology was pT3b ccRCC, ISUP Grade 2, with protrusion into the IVC, Negative surgical margins for primary specimen and for distal caval margin. Her postoperative creatinine was 1.07 (eGFR 51) – compared to 0.97 (eGFR 57) pre-op.

His take-home messages:

  • Partial Nephrectomy does not harm oncological outcomes in select patients
  • May have benefit with primary tumors
  • In an era characterized by more effective systemic therapies with better oncologic outcomes (and longer survival),
    • CPN for imperative indications is safe and feasible for larger and complex renal masses
    • Long-term impact of functional decline in metastatic patients is not characterized

Presented by: Ithaar H. Derweesh, MD, Urologic Oncologist, UC San Diego

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd @UCDavisUrology on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023 

References:

  1. Capitanio U, Zini L, Perrotte P, Sariat SF, Jeldres C, Arjane P, Pharand D, Widmer H, Péloquin F, Montorsi F, Patard JJ, Karakiewicz PI. Cytoreductive partial nephrectomy does not undermine cancer control in metastatic renal cell carcinoma: a population-based study. Urology. 2008 Nov;72(5):1090-5. doi: 10.1016/j.urology.2008.06.059. Epub 2008 Sep 16. PMID: 18799207.
  2. Silberstein JL, Millard F, Mehrazin R, Kopp R, Bazzi W, DiBlasio CJ, Patterson AL, Downs TM, Yunus F, Kane CJ, Derweesh IH. Feasibility and efficacy of neoadjuvant sunitinib before nephron-sparing surgery. BJU Int. 2010 Nov;106(9):1270-6. doi: 10.1111/j.1464-410X.2010.09357.x. PMID: 20394613.
  3. Shemshaki H, Al-Mamari SA, Al-Hooti Q, Geelani IA, Al Salmi I, Narayana Kurukkal S, Kumar S, Al Julandani A, Sadeghzadeh S. Comparison of cytoreductive partial versus radical nephrectomy in metastatic renal cell carcinoma: To be on the horns of a dilemma. Urologia. 2022 May;89(2):160-166. doi: 10.1177/03915603221092096. Epub 2022 Apr 15. PMID: 35422178.
  4. Lenis AT, Salmasi AH, Donin NM, Faiena I, Johnson DC, Drakaki A, Gollapudi K, Blumberg J, Belldegrun AS, Pantuck AJ, Chamie K. Trends in usage of cytoreductive partial nephrectomy and effect on overall survival in patients with metastatic renal cell carcinoma. Urol Oncol. 2018 Feb;36(2):78.e21-78.e28. doi: 10.1016/j.urolonc.2017.09.030. Epub 2017 Nov 8. PMID: 29128421.
  5. Dey S, Hamilton Z, Noyes SL, Tobert CM, Keeley J, Derweesh IH, Lane BR. Chronic Kidney Disease Is More Common in Locally Advanced Renal Cell Carcinoma. Urology. 2017 Jul;105:101-107. doi: 10.1016/j.urology.2017.03.033. Epub 2017 Mar 30. PMID: 28365357.