ASCO 2018: Role of Surgery in Management of High-Risk Renal Cell Cancer

Chicago, IL ( In this two part educational session, Drs. Rini and Kim discuss the role of peri-operative systemic therapy for localized renal cell carcinoma. Dr. Kim discussed the role of surgery in the management of high-risk localized RCC.
Some of the data he touched upon overlapped with Dr. Rini’s talk, so it will not be repeated here. I highlight some of the important points he makes from his talk specifically.

The use of adjuvant TKI for high-risk localized RCC is very controversial, as reflected by the high degree of clinical practice and expert opinion. He notes that even the FDA advisory board on whether to approve sunitinib in the adjuvant setting based on S-TRAC data was split evenly – 6 for and 6 against. While it was still approved, it is recommended as category 2b in NCCN guidelines, secondary to clinical trial enrollment. The lack of certainty is also reflected by the fact that the SOC arms for clinical trials initiated after that decision still consisted of placebo – not sunitinib.

S-TRAC eligibility was:
⁃ Pathologic T3/T4 disease and N+ disease
⁃ Clear cell histology
⁃ ECOG PS <= 2
⁃ No macroscopic residual disease

Dr. Kim’s first point is counseling. When first seeing a patient in clinic prior to an operation, is there any way to predict the need for adjuvant therapy?
⁃ Primary tumor size is strongly correlated with pT3 disease and can be used to guide the discussion
• Tumors > 6 cm in size have a >40% change of pT3 disease
• These patients can be warned ahead of time that adjuvant therapy may be recommended after surgery
⁃ Unfortunately, other markers, such as radiographic (perinephric stranding, etc) have not be reliably associated with pathologic grade

His next surgical focus was on the importance of lymphadenectomy in these patients. Prior to S-TRAC, lymphadenectomy maybe affected staging, but did not necessarily have treatment implications. But since S-TRAC includes N+ disease, patients with N+ disease may be candidates for an FDA-approved therapy or clinical trial – however, if patients don’t get a lymphadenectomy, then they can never be a candidate for therapy!
⁃ Patients who are cT2N0 still have a risk of being pN+
⁃ Multiple studies have demonstrated that clinical staging is not perfect for RCC
⁃ pN+ rates are approximately 10% in cN0 patients
To that effect, and based on his clinical experience (Chapman and Kim, Urology 2008) of 16% pN+ disease in patients who were cN0, he does a LND in all patients undergoing radical nephrectomy. He does not do it for patients undergoing partial nephrectomy.
⁃ He feels that if they warrant a radical nephrectomy then they are inherently at risk for nodal disease
⁃ If they don’t get a node dissection, they may be missing out on an opportunity to get adjuvant therapy
⁃ His node dissection is an ipsilateral template mimicking an rplnd

His next point is that in S-TRAC, patients went on to adjuvant therapy 3-12 weeks post-operatively. So, time to recovery is important. He usually tells his patients that for every day spent in the hospital post-operatively, there is an additional 2 weeks of recovery at home. As can be expected, patients with more advanced disease have bigger operations and longer recovery – so some of them may not fall in the window of adjuvant therapy depending on their recovery.

He lastly spent some time again reiterating the uniqueness of the PROSPER study (ASCO 2018 Abstract TPS 4597), which treats patients with nivolumab 2 cycles prior to nephrectomy in the hopes that it primes the system. They are the subsequently treated with adjuvant nivolumab after nephrectomy. These will be interesting results!

In his practice, he feels it is important to discuss and offer sunitinib to all high-risk (S-TRAC criteria) patients and let them make the decision. As an approved therapy, it is important that it is discussed. He also tries to put patients on clinical trials first.

Presented by: Hyung Kim, MD

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA

Read the Corresponding Discussion:

Systemic Therapy in Management of High-Risk Renal Cancer - Presented by: Brian Rini, MD Brian Rini, MD