Evolving biological associations of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma Journal Article


Authors: Silagy, A. W.; Kotecha, R. R.; Weng, S.; Holmes, A.; Singla, N.; Mano, R.; Attalla, K.; Weiss, K. L.; DiNatale, R. G.; Patil, S.; Coleman, J. A.; Motzer, R. J.; Russo, P.; Voss, M. H.; Hakimi, A. A.
Article Title: Evolving biological associations of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma
Abstract: Background: Systemic responses to cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) are variable and difficult to anticipate. The authors aimed to determine the association of CN with modifiable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors and oncological outcomes. Methods: Consecutive patients with mRCC referred for potential CN (2009-2019) were reviewed. The primary outcome was overall survival (OS); variables of interest included undergoing CN and the baseline number of modifiable IMDC risk factors (anemia, hypercalcemia, neutrophilia, thrombocytosis, and reduced performance status). For operative cases, the authors evaluated the effects of IMDC risk factor dynamics, measured 6 weeks and 6 months after CN, on OS and postoperative treatment disposition. Results: Of 245 treatment-naive patients with mRCC referred for CN, 177 (72%) proceeded to surgery. The CN cases had fewer modifiable IMDC risk factors (P =.003), including none in 71 of 177 patients (40.1%); fewer metastases (P =.011); and higher proportions of clear cell histology (P =.012). In a multivariable analysis, surgical selection, number of IMDC risk factors, metastatic focality, and histology were associated with OS. Total risk factors changed for 53.8% and 57.2% of the patients from the preoperative period to 6 weeks and 6 months after CN, respectively. Adjusted for preoperative IMDC risk scores, an increase in IMDC risk factors at 6 weeks and 6 months was associated with adverse OS (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.13-2.19; P =.007; HR, 2.52; 95% CI, 1.74-3.65; P <.001). Conclusions: IMDC risk factors are dynamic clinical variables that can improve after upfront CN in select patients, and this suggests a systemic benefit of cytoreduction, which may confer clinically meaningful prognostic implications. © 2021 American Cancer Society
Keywords: adult; controlled study; treatment outcome; aged; middle aged; major clinical study; overall survival; patient selection; treatment duration; cytoreductive surgery; anemia; cohort analysis; hypercalcemia; histology; renal cell carcinoma; nephrectomy; adverse outcome; preoperative period; surgical risk; risk stratification; kidney metastasis; physical performance; patient referral; thrombocytosis; cytoreductive nephrectomy; neutrophilia; cancer prognosis; human; male; female; article; population structure
Journal Title: Cancer
Volume: 127
Issue: 21
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2021-11-01
Start Page: 3946
End Page: 3956
Language: English
PMCID: PMC8516697
DOI: 10.1002/cncr.33790
PROVIDER: scopus
PUBMED: 34286865
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Jonathan Coleman
    346 Coleman
  2. Sujata Patil
    511 Patil
  3. Paul Russo
    582 Russo
  4. Robert Motzer
    1247 Motzer
  5. Martin Henner Voss
    292 Voss
  6. Abraham Ari Hakimi
    327 Hakimi
  7. Roy Mano
    52 Mano
  8. Andrew William Silagy
    33 Silagy
  9. Ritesh Rajesh Kotecha
    94 Kotecha
  10. Nirmish Singla
    17 Singla
  11. Kyrollis Attalla
    19 Attalla
  12. Stanley Weng
    11 Weng
  13. Kate Weiss
    10 Weiss