Management of High-risk Localized Kidney Cancer

September 2017

Case of the Month Management of High-risk Localized Kidney Cancer NYU Case of the Month, September 2017 William C. Huang, MD Department of Urology, NYU Langone Medical Center, New York, NY [Rev Urol. 2017;19(3):187–189 doi: 10.3909/riu1903NYUSept] ® © 2017 MedReviews , LLC Case Presentation A 53-year-old woman with past medical history significant for tobacco use presents for evaluation and recommendations regarding an incidental left kidney mass. She had undergone an abdominal ultrasound for right-sided abdominal pain and was noted to have an incidental left kidney mass. This was confirmed on a CT scan of the abdomen/ pelvis, demonstrating a 3.4-cm partially exophytic mass in the left kidney, possibly containing bulk fat, abutting the renal sinus fat (Figure 1). Relevant Prior History and Evaluation Tobacco use s/p Hysterectomy s/p Appendectomy Cr/eGFR 2017: 0.7 mg/dL/.60 mL/min /1.73 m2 UA 2017: No proteinuria Figure 1. Vol. 19 No. 3 • 2017 • Reviews in Urology • 187 Management of High-risk Localized Kidney Cancer continued Inspection of the vein stump did not demonstrate any residual disease, and the robotic partial nephrectomy was completed as planned (Figure 3). Final Pathology Diagnosis: pT3aNxMx Clear cell RCC; negative surgical margins Post-op Cr/eGFR: 0.7 mg/dL/ .60 mL/min/1.73 m2 Figure 2. Physical Examination Abdomen: Soft, no palpable masses Evaluation at NYU Langone Health Images were reviewed, and given the finding of possible fat within the mass, a renal mass biopsy was performed to confirm the diagnosis of a renal angiomyolipoma (Figure 2). Diagnosis: Clear cell renal cell carcinoma (RCC) Management The patient underwent an uncomplicated robotic partial nephrectomy for a biopsy-proven RCC. Intra-operatively, the tumor was noted to have a small extension into a segmental renal vein. The tumor and the tumor thrombus were completely excised. Given the elevated risk of recurrence in stage III RCC, the patient decided to enroll in a phase III clinical trial (IMmotion010) using adjuvant atezolizumab (PD-L1 inhibitor), which is being offered at NYU Langone Health’s Perlmutter Cancer Center. Comment More than 70% of newly diagnosed kidney masses are found incidentally on imaging for unrelated causes. Subsequently, most newly diagnosed kidney cancers are localized, are ,4 cm, and, in surgical candidates, are managed with partial nephrectomy, given oncologic equivalency to radical nephrectomy, with superior kidney function outcomes.1 Imaging alone is frequently sufficient to diagnose a kidney cancer, and routine renal mass biopsy is not commonly indicated since it does not alter management.2 In this case, however, given the Figure 3. 188 • Vol. 19 No. 3 • 2017 • Reviews in Urology radiographic findings suggestive of a renal angiomyolipoma, the renal biopsy findings demonstrated a clear cell RCC, prompting surgical treatment. Data from our institution demonstrates that up to 13% of cT1 (,7 cm) tumors are upstaged to pT3a following nephrectomy (because of occult fat involvement or segmental vein involvement). In the setting of a complete resection, treatment with partial nephrectomy did not demonstrate a greater risk of local recurrence.3 Thus, it was decided intra-operatively to complete the elective partial nephrectomy. The current standard of care for patients with nonmetastatic RCC, including those with high-risk features such as vein involvement, is observation. However, since up to 20% of patients may develop a recurrence following surgery, there is an indication for adjuvant therapy in high-risk patients. The use of tyrosine kinase inhibitors (TKIs) in the adjuvant setting has had mixed results at best, with considerable side effects. Therefore, there is a great deal of interest in using immunotherapy in patients with high-risk nonmetastatic kidney cancer. Prior to the development of TKIs, immunotherapy with either interferon alpha or high-dose interleukin-2 was the only available nonsurgical treatment option for metastatic RCC. With the known role of tumor immunity in RCC, along with the breakthrough success of immunotherapy agents known as checkpoint inhibitors in other malignancies, various checkpoint inhibitors are being evaluated in patients with metastatic RCC in both first-line and second-line settings. Nivolumab (PD-1 inhibitor) received FDA approval as second-line treatment for metastatic RCC in 2015.4 The promising results of checkpoint inhibitors in metastatic RCC Management of High-risk Localized Kidney Cancer have led to the development of phase III trials involving checkpoint inhibitors in the adjuvant setting. This patient chose to enroll in IMmotion010, a multicenter, randomized, placebo-controlled, double-blind study of atezolizumab as adjuvant therapy in patients with RCC at high risk of developing metastasis following nephrectomy, being offered at NYU Langone Health.5 With the rapidly changing landscape of novel agents available for the treatment of RCC, it is critical for patients with high-risk kidney cancer to be aware that there are other options besides observation following surgery. Surgeons are encouraged to learn more about these treatment options and to consider enrolling their patients in one of these potentially paradigm changing clinical trials. ■ References 1. 2. 3. 4. 5. Kang SK, Huang WC, Pandharipande PV, Chanda­ rana H. Solid renal masses: what the numbers tell us. AJR Am J Roentgenol. 2014;202:1196-1206. Ramaswamy K, Kheterpal E, Pham H, et al. Significance of pathologic T3a upstaging in clinical T1 renal masses undergoing nephrectomy. Clin Genitourin Cancer. 2015;13:344-349. Motzer RJ, Escudier B, McDermott DF, et al; CheckMate 025 Investigators. Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373:1803-1813. A study of atezolizumab as adjuvant therapy in participants with renal cell carcinoma (RCC) at high risk of developing metastasis following nephrectomy (IMmotion010). ClinicalTrials.gov website. https://clinicaltrials.gov/show/NCT03024996. Updated August 1, 2016. Accessed August 28, 2017. Huang WC, Atoria CL, Bjurlin M, et al. Management of small kidney cancers in the new millennium: contemporary trends and outcomes in a population-based cohort. JAMA Surg. 2015;150:664-672. Vol. 19 No. 3 • 2017 • Reviews in Urology • 189