After the publication of the CARMENA findings1 that questioned the survival benefit of cytoreductive nephrectomy in contemporary metastatic renal cell carcinoma patients, the role of cytoreductive nephrectomy has been debated. The concerns about the use of cytoreductive nephrectomy may be even more prominent when considering older patients. Since no contemporary data exists to specifically ascertain complication and in-hospital mortality in older patients, we reassessed complication and mortality rates after cytoreductive nephrectomy in a contemporary cohort of older patients with metastatic renal cell carcinoma identified within the National Inpatient Sample database (2008-2015).2
Conversely from previous studies, alongside well-established prognostic factors, such as age and comorbidities, for the first time, we also investigated specific issues that apply to geriatric patients, such as frailty and its components. Specifically, we tested the effect of age (≤55 years vs. 56-70 years vs. ≥71 years), Charlson (CCI 0 vs CCI 1 vs. CCI ≥2) and frailty (frail vs. non-frail) on overall complications, failure to rescue and in-hospital mortality. We relied on the Johns Hopkins ACG frailty-defining diagnosis indicator-based definition of frailty3 that allows accounting for cognitive, functional and social impairments since it encompasses dementia, vision impairment, malnutrition, urinary and fecal incontinence, difficulty in walking, falls and social support needs. Since frailty and comorbidities did not overlap, we were able to capture the different effect of comorbidity and frailty.
Our analyses showed that frailty was the strongest independent predictor of overall complications (odds ratio [OR] 1.91, p<0.001), followed by Charlson ≥2 (OR 1.88, p<0.001) and age ≥71 (OR 1.4, p<0.001), after simultaneous consideration of these three variable and multivariable adjustment for other patient and hospital characteristics. Conversely, neither Charlson nor frailty reached independent predictor status in failure to rescue and in-hospital mortality analyses, after adjustment for age. Nonetheless, age did emerge as an independent predictor in failure to rescue but not in-hospital mortality. Although Charlson and frailty were only associated with overall complications, these important variables should be taken into account in all analyses, as well as everyday clinical practice.
Our findings highlight the importance of rigorous selection criteria for surgical candidates that should be based not only on age but also on comorbidities and frailty. These patients should be ideally referred to multimodal prehabilitation programs, including exercise, nutrition, and psychological interventions, that could potentially improve the perioperative outcomes of these patients.4 Nonetheless, the underlying disease may not often allow an eight-week delay prior to surgery. In consequence, alongside with age also frailty and comorbidities might not be modifiable. A careful discussion about goals of care could help patients have realistic expectations and make better-informed decisions before the surgery.
Written by: Carlotta Palumbo, MD and Pierre I. Karakiewicz, MD, Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada Twitter: @CPalumbo87, @sophieknipper, @AngelaPecoraro3, @DrShariat, @ABrigantiMD, @aleantonellibs1, @pikarakiewicz,
References:
1. Méjean A, Ravaud A, Thezenas S, Colas S, Beauval J-B, Bensalah K, et al. Sunitinib Alone or after Nephrectomy in Metastatic Renal-Cell Carcinoma. N Engl J Med 2018;379:417–27. doi:10.1056/NEJMoa1803675.
2. Palumbo C, Knipper S, Dzyuba-Negrean C, Pecoraro A, Rosiello G, Tian Z, et al. Complication rates, failure to rescue and in-hospital mortality after cytoreductive nephrectomy in the older patients. J Geriatr Oncol 2019:S1879406819301961. doi:10.1016/j.jgo.2019.06.005.
3. Kim DH, Schneeweiss S. Measuring Frailty Using Claims Data for Pharmacoepidemiologic Studies of Mortality in Older Adults: Evidence and Recommendations. Pharmacoepidemiol Drug Saf 2014;23:891–901. doi:10.1002/pds.3674.
4. Alvarez-Nebreda ML, Bentov N, Urman RD, Setia S, Huang JC-S, Pfeifer K, et al. Recommendations for Preoperative Management of Frailty from the Society for Perioperative Assessment and Quality Improvement (SPAQI). J Clin Anesth 2018;47:33–42. doi:10.1016/j.jclinane.2018.02.011.