ASCO GU 2020: Best of the Journals – Renal Cell Carcinoma: Surgery Perspective

• Those that inform decision making for localized RCC  partial vs radical nephrectomy
• Neoadjuvant targeted kinase inhibitors (TKIs) to increase surgical feasibility for complex nephron-sparing surgery
• Expand our understanding of RCC follow-up after surgery, which may lead to questioning the current guideline recommendations

The first study selected by Dr. Merrill assessed the possible survival benefit for partial nephrectomy among patients without pre-existing chronic kidney disease.¹ This study retrospectively evaluated 3,133 patients with a preoperative glomerular filtration rate of 60 ml/minute/1.73 m² or greater who underwent partial or radical nephrectomy. The median preoperative glomerular filtration rate was 85 ml/minute/1.73 m², and the new baseline glomerular filtration rate was 80 for patients after partial nephrectomy and 63 ml/minute/1.73 m² for patients after radical nephrectomy. The 10-year nonrenal cancer-related mortality was 11.3% for those undergoing partial nephrectomy and 17.7% after radical nephrectomy (all p <0.001). Over a median follow-up of 9.3 years, nonrenal cancer-related mortality was similar in all patients with a new baseline glomerular filtration rate of 45 ml/minute/1.73 m² or greater (p = 0.26). However, nonrenal cancer mortality increased 50% or more in the 290 patients with a new baseline below baseline glomerular filtration rate of 45 ml/minute/1.73 m² (p = 0.001). In patients with a new baseline greater than 45 ml/minute/1.73 m² 10-year nonrenal cancer related mortality was still substantially improved after partial nephrectomy (10.6% vs 16.3%, p <0.001). Dr. Merrill’s take-home messages for this study are as follows:

• The surgical goal is to keep GFR > 45 mL/min/1.73 m² – we should prioritize partial nephrectomy to accomplish this GFR goal
• The survival advantage with partial nephrectomy is not due to better post-surgical GFR and the outcome may be influenced by selection bias

The second study selected by Dr. Merrill assessed the association between partial versus radical nephrectomy with subsequent hypertension.² Shah et al. used a national administrative database of privately and Medicare insured patients to perform a retrospective cohort study of 9,207 patients undergoing radical nephrectomy and 4,686 patients who underwent partial nephrectomy. Primary outcomes included new onset hypertension among patients with no history of hypertension and worsened hypertension among patients with baseline hypertension. Among 3,106 propensity-matched patients without preexisting hypertension, radical nephrectomy was associated with a higher risk of new onset hypertension compared to partial nephrectomy (HR 1.40, 95% CI 1.22-1.60, p <0.001). Similarly, among 6,250 propensity-matched patients with hypertension prior to surgery radical nephrectomy was associated with a higher risk of worsening baseline hypertension (HR 1.18, 95% CI 1.10-1.26, p <0.001). Dr. Merrill’s take-home message from this study is that radical nephrectomy portends a greater risk of new hypertension, as well as worse hypertension among those with a history of hypertension. Furthermore, these results held for patients ≥75 years of age and those with normal preoperative renal function. As such, for localized disease, we should use partial nephrectomy whenever feasible.

The third study selected by Dr. Merrill evaluated axitinib to downstage cT2a renal tumors and allow partial nephrectomy.³ Patients with cT2aN0NxM0 clear-cell RCC, considered not suitable for partial nephrectomy, were enrolled in the prospective, multicenter, phase II AXIPAN trial. Axitinib 5 mg, and up to 7-10 mg, was administered twice daily, for 2-6 months before surgery, depending on the radiological response. Among 18 patients enrolled, the median tumour size was 76.5 mm (range 70-98) and RENAL nephrometry score was 11 (range 7-11). After axitinib neoadjuvant treatment, 16 tumors decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm). There were 12 patients who underwent PN for tumours <7 cm and 16 patients underwent partial nephrectomy overall. Dr. Merrill’s take-home messages for this study included:

• Neoadjuvant axitinib may improve the feasibility of complex nephron-sparing surgery
• This is an exciting future option when radical nephrectomy needs to be avoided
• Further investigation is warranted and outcomes will still rely on surgeon experience
• More robust evidence is coming soon with the PADRES (Prior Axitinib as a Determinant of Outcome of Renal Surgery) trial

The final study Dr. Merrill discussed was a post-hoc analysis of the E2805 trial assess long-term risk of recurrence in surgically treated RCC patients [4]. The 36-month cumulative incidence of recurrence was assessed at set intervals following surgery, in order to assess recurrence through the use of a conditional survival model. Of the 1,943 patients (pT1b or greater) included in the original cohort, 730 developed recurrence. The 36-month cumulative incidences of recurrence following surgery were as follows:

• 0 months: 31%
• 12 months: 26%
• 24 months: 19%
• 36 months: 16%
• 48 months: 19%
• 60 months: 20%

At 0 months from surgery, age, pathological T3/4 stage, pathological N1/2 stage, and Fuhrman grades 3 and 4 were independent predictors of recurrence; however, this was not seen at 60 months following surgery. The highlights of this study according to Dr. Merrill were as follows:

• There is a major drop in recurrence risk after 2 year following surgery and the risk remains stable thereafter
• However, even at 5 years there is still a ~20% risk of recurrence remaining
• This data supports continuing follow-up beyond 5 years
• Known predictors of recurrence lose their predictive power at 60 months

Presented by: Suzanne Merrill, MD, Urologic Oncologist, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania

1. Suk-Ouichai C, Tanaka H, Wang Y, et al. Renal cancer surgery in patients without preexisting chronic kidney disease—Is there a survival benefit for partial nephrectomy? J Urol 2019 Jun;201(6):1088-1096.
2. Shah PH, Leibovich BC, Van Houten H, et al. Association of partial versus radical nephrectomy with subsequent hypertension risk following renal tumor resection. J Urol 2019 Jul;202(1):69-75.
3. Lebacle C, Bensalah K, Bernhard JC, et al. Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: A phase II study. BJU Int 2019 May;123(5):804-810.
4. Jamil ML, Keeley J, Sood A, et al. Long-term risk of recurrence in surgically treated renal cell carcinoma: A post hoc analysis of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E2805 trial cohort. Eur Urol 2020 Feb;77(2):277-281.