|Metastatic renal cancer.|
(7, 8). While the results of these trials are pending, a few retrospective studies have suggested improved survival in patients undergoing CN + targeted therapy (9, 10).
Selecting Patients for Cytoreductive NephrectomyIn addition to determining the value of CN in the new era of targeted therapy, patient selection criteria for CN in this era also needs to be determined. Evidence from the cytokine therapy era indicated that patients with lung-only metastases, ECOG performance status scores of 0-1, and good prognostic factors were the most likely to benefit from surgery (2). While several studies have sought to further define favorable and unfavorable prognostic factors (such as the presence of liver metastases, low albumin levels, T3/T4 clinical stage, etc.) (11), there is a paucity of dedicated patient selection studies specifically in the targeted therapy era. Understanding which patients would most benefit from surgery in the context of targeted therapy is important because some patients may not be able to receive systemic therapy after undergoing an operation. In fact, a recent retrospective study indicated that approximately 1/3 of patients who undergo CN do not ultimately receive systemic therapy; the most common reasons were rapid disease progression (30%), decision for surveillance by medical oncologist (21%), and perioperative mortality (19%) (12). While all the patients who had rapid disease progression had either high grade tumor or sarcomatoid differentiation, on multivariate analysis, ECOG performance status was the only covariate significantly associated with whether or not a patient received or was eligible to receive systemic therapy after CN (12). While ECOG performance status scores may be helpful in predicting which patients with metastatic disease are good surgical candidates, the metric itself certainly has its limitations, as it is subjective and can be susceptible to considerable inter-rater variability (13). Given the limitations of the ECOG performance metric, an evaluation of alternate metrics to inform pre-operative risk stratification is warranted.
Frailty and SarcopeniaFrailty is a potential alternate metric that could help to better elucidate patient selection for CN in the targeted therapy era. Frailty is a concept originally conceived and validated in the geriatrics literature. It is a novel domain of risk that captures decreased physiologic reserve and is a construct that is independent of comorbidity and disability (14). Frailty is based on five components defined by the Fried criteria: shrinking, weakness, exhaustion, low physical activity, and slowed walking speed (14). Frailty has been shown to be an independent predictor of post-operative outcomes in the general surgery and transplant populations. For example, in kidney transplant recipients, we have shown that frailty is independently associated with poor outcomes, including early hospital readmissions, delayed graft function, and mortality (15-17). While frailty is not routinely measured in the clinical setting, sarcopenia is a radiographic correlate of frailty that is assessed on CT imaging and is, therefore, more readily available in our surgical patients. Sarcopenia (the degenerative loss of skeletal muscle) is based on core lean muscle size, and, like the Fried index, it has also been shown to be an independent predictor of post-operative outcomes in the general surgery and transplant populations (18, 19).
|The psoas muscles (highlighted in blue) are a |
common measure of sarcopenia.
This blog was written by Natasha Gupta, Medical Student at Johns Hopkins Medical School. Natasha recently finished a four-week sub-internship at the Brady Urological Institute and gave a presentation to the department on "Metastatic Renal Cell Carcinoma: Cytoreductive Nephrectomy" from which this blog is inspired. Natasha is looking forward to a career in urology.
1. Lam JS, Shvarts O, Leppert JT, Figlin RA, Belldegrun AS: Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy. The Journal of urology, 173: 1853-1862, 2005
2. National Comprehensive Cancer Network. Kidney Cancer (Version 3.2014),
3. Pantuck AJ, Belldegrun AS, Figlin RA: Nephrectomy and interleukin-2 for metastatic renal-cell carcinoma. The New England journal of medicine, 345: 1711-1712, 2001
4. Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR, Jr., Munshi N, Crawford ED: Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. The New England journal of medicine, 345: 1655-1659, 2001
5. Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R, European Organisation for R, Treatment of Cancer Genitourinary G: Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet, 358: 966-970, 2001
6. Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED: Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. The Journal of urology, 171: 1071-1076, 2004
7. clinicaltrials.gov, 2013
8. clinicaltrials.gov, 2012
9. Choueiri TK, Xie W, Kollmannsberger C, North S, Knox JJ, Lampard JG, McDermott DF, Rini BI, Heng DY: The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. The Journal of urology, 185: 60-66, 2011
10. You D, Jeong IG, Ahn JH, Lee DH, Lee JL, Hong JH, Ahn H, Kim CS: The value of cytoreductive nephrectomy for metastatic renal cell carcinoma in the era of targeted therapy. The Journal of urology, 185: 54-59, 2011
11. Culp SH, Tannir NM, Abel EJ, Margulis V, Tamboli P, Matin SF, Wood CG: Can we better select patients with metastatic renal cell carcinoma for cytoreductive nephrectomy? Cancer, 116: 3378-3388, 2010
12. Kutikov A, Uzzo RG, Caraway A, Reese CT, Egleston BL, Chen DY, Viterbo R, Greenberg RE, Wong YN, Raman JD, Boorjian SA: Use of systemic therapy and factors affecting survival for patients undergoing cytoreductive nephrectomy. BJU international, 106: 218-223, 2010
13. Sorensen JB, Klee M, Palshof T, Hansen HH: Performance status assessment in cancer patients. An inter-observer variability study. British journal of cancer, 67: 773-775, 1993
14. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research G: Frailty in older adults: evidence for a phenotype. The journals of gerontology Series A, Biological sciences and medical sciences, 56: M146-156, 2001
15. McAdams-DeMarco MA, Law A, Salter ML, Boyarsky B, Gimenez L, Jaar BG, Walston JD, Segev DL: Frailty as a novel predictor of mortality and hospitalization in individuals of all ages undergoing hemodialysis. Journal of the American Geriatrics Society, 61: 896-901, 2013
16. McAdams-DeMarco MA, Law A, Salter ML, Chow E, Grams M, Walston J, Segev DL: Frailty and early hospital readmission after kidney transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 13: 2091-2095, 2013
17. Garonzik-Wang JM, Govindan P, Grinnan JW, Liu M, Ali HM, Chakraborty A, Jain V, Ros RL, James NT, Kucirka LM, Hall EC, Berger JC, Montgomery RA, Desai NM, Dagher NN, Sonnenday CJ, Englesbe MJ, Makary MA, Walston JD, Segev DL: Frailty and delayed graft function in kidney transplant recipients. Archives of surgery, 147: 190-193, 2012
18. Englesbe MJ, Patel SP, He K, Lynch RJ, Schaubel DE, Harbaugh C, Holcombe SA, Wang SC, Segev DL, Sonnenday CJ: Sarcopenia and mortality after liver transplantation. Journal of the American College of Surgeons, 211: 271-278, 2010
19. Sabel MS, Terjimanian M, Conlon AS, Griffith KA, Morris AM, Mulholland MW, Englesbe MJ, Holcombe S, Wang SC: Analytic morphometric assessment of patients undergoing colectomy for colon cancer. Journal of surgical oncology, 108: 169-175, 2013
20. Antoun S, Lanoy E, Iacovelli R, Albiges-Sauvin L, Loriot Y, Merad-Taoufik M, Fizazi K, di Palma M, Baracos VE, Escudier B: Skeletal muscle density predicts prognosis in patients with metastatic renal cell carcinoma treated with targeted therapies. Cancer, 119: 3377-3384, 2013
21. Cushen SJ, Power DG, Teo MY, Maceneaney P, Maher MM, McDermott R, O'Sullivan K, Ryan AM: Body Composition by Computed Tomography as a Predictor of Toxicity in Patients With Renal Cell Carcinoma Treated With Sunitinib. American journal of clinical oncology, 2014
22. Psutka SP, Carrasco A, Schmit GD, Moynagh MR, Boorjian SA, Frank I, Stewart SB, Thapa P, Tarrell RF, Cheville JC, Tollefson MK: Sarcopenia in patients with bladder cancer undergoing radical cystectomy: Impact on cancer-specific and all-cause mortality. Cancer, 2014