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Renal Cell Carcinoma
Center of Excellence
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George Yaghmour
Jul 21, 2015
Limited data for Nephron Sparing Surgery (NSS) in the setting of metastatic RCC, all the available studies I mentioned here in my comment are retrospective, and relied on a small number of highly selected patients. This significant selection bias may be attributed to the fact that NSSs were performed for imperative indications, such as solitary kidney, bilateral disease or CKD. In Culp SH et al. papers patients most likely to benefit from cytoreductive nephrectomy before systemic therapy are those with lung-only metastases, good prognostic features, and good performance status. Licht et al demonstrated a significantly increased 5-year cancer-specific survival rate and decreased tumor recurrence rate in incidental versus symptomatic RCC lesions. Shahait, M et al. and his associates performed a systematic review of the literatures, which demonstrated that Patients most likely to benefit from a NSS are those for whom RN is not feasible due to preexisting renal impairment, and patients with limited metastatic disease expected to enjoy prolonged survival with a combination surgical intervention and systemic therapy. No prospective studies examining the efficacy and safety of tyrosine kinase inhibitors in patients with metastatic RCC and CKD, patients with preserved nephron volume may tolerate tyrosine kinase inhibitors with fewer complications. Parasa et al. reported that Grade I and II adverse effects of sorafenib were more frequent in CKD patients. Serious adverse effects of TKI in CKD patients, such as subarchanoid hemorrhage, cerebellar hemorrhage, myocardial infarction, congestive heart failure and pancreatitis, were reported. Kamberk et al. reviewed the Mayo Clinic Nephrectomy Registry between 1970 and 2002, the major drawback of this study is that 87.5% of the patients in the NSS group underwent complete resection of all metastatic disease compared with 22.5% from the RN group; hence, comparing disease-specific survival of both groups may be confounded. Capitanio et al. re-examined the effect of NSS on RCC-specific survival relative to RN using the SEER cancer registries from1988 to 2004, a total of 2043 patients with metastatic disease underwent cytoreductive nephrectomy, it was concluded that NSS was not associated with worse RCC-specific survival compared with RN. Hellenthal et al. identified 56,011 patients with RCC who were also registered in the SEER database between 1988 and 2005 on multivariate analysis, patients undergoing RN were at a two-time higher risk of dying from mRCC than those undergoing NSS.
In this case the patient was asymptomatic, and diagnosed incidentally by surveillance Scan, with resectable smaller than 4 cm kidney mass and solitary lung disease. He has only one kidney. This recurrent potentially surgically resectable primary with solitary metastatic site, with no high risk features and very good performance status. In this case would suggest the need of a tissue biopsy of the recurrent disease with molecular studies (Carris or foundation one) for potential future Immunotherpay trial or targeted therapy. According to NCCN guidelines and literature review I would consider Partial Nephrectomy with surgical or RFA metastasectomy with curative intent. Either close follow up or Adjuvant Sunitinib per S-TRAC trial. Sunitinib systemic treatment is an option if surgery is risky and could not spare the remaining kidney function. However there is no prospective good evidence so far for adjuvant targeted therapy and adding Sunitinib after surgery is controversial, with no well known risk of toxicities in the setting of possible kidney dysfunction after the surgery. However, Sunittinib after RSS is an option here. The current large adjuvant Sunitinib trial S-TRAC in RCC are currently being conducted, with a primary endpoint of either disease-free survival (DFS) or recurrence-free survival and with placebo as the control arm, and results would answer this question.
There is also a conflict and limited data of the effectiveness of cytoreductive nephrectomy in the setting of targeted therapy in mRCC, but the ongoing CARMENA trial in Europe, where patients are randomized to upfront cytoreductive nephrectomy followed by treatment with Sunitinib versus treatment with Sunitinib alone, may resolve this debate and answer more the question if need surgery or just sunitinib therapy.
George Yaghmour
Jul 22, 2015
I would follow my comment with a conclusion that the approach of nephron sparing surgery followed by Sunitinib therapy is really appealing and reasonable to me and agree with this approach given this patient characteristics, assuming he has very good performance status ad he has no high risk features. The Sunitinib metabolite extensively by Liver CYP450:3A4 and 61% is excreted by feces with 16% kidney excretion. Eventhough we have limited data and all are retrospective and reviewing the Culp SH et al. papers and Shahait, M et al. systematic review awaiting the results of CARMENA trial I would agree of partial nephroctomy and follow up with Sunitinib.
Dec 24, 2024
Pending Moderator approval.
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George Yaghmour
Jul 21, 2015
George Yaghmour
Jul 22, 2015
Dec 24, 2024
Pending Moderator approval.