EAU24 Expert Review | Professor Qiang Wei: Multimodal Treatment of Renal Cancer from a Surgical Perspective

Editorial Note: The treatment of renal cancer includes surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy. With advancements in treatment technologies, combining the latest modalities for comprehensive treatment of renal cancer is crucial for improving prognosis. The 39th Annual European Association of Urology (EAU24) Congress was held from April 5-8, 2024, in Paris, France, focusing on global urological oncology hotspots and forefront advancements from Chinese urological scholars. “Oncology Frontier” had the opportunity to interview Professor Qiang Wei from West China Hospital, Sichuan University, who shared insights into adjuvant immunotherapy for renal cancer, cytoreductive nephrectomy research, and robot-assisted radical nephrectomy.

Oncology Frontier: Based on the KEYNOTE-564 study, early adjuvant immunotherapy for renal cancer has commenced. Could you discuss your views on adjuvant immunotherapy for renal cancer, considering recent studies and updates from the EAU24?

Professor Qiang Wei: The field of adjuvant therapy for renal cancer has recently seen significant advancements. The KEYNOTE-564 study is the first phase III study to report positive results for adjuvant immunotherapy in renal cancer. In 2021, ASCO reported 24-month follow-up data [1], showing a 32% reduction in disease progression risk with pembrolizumab (HR 0.68, P=0.001). The 2024 ASCO-GU meeting reported 57-month follow-up data [2], achieving a significant improvement in OS (HR 0.62, P=0.0024) while maintaining consistent DFS benefits (HR=0.72). The KEYNOTE-564 study included both M0 and M1 patients with no evidence of disease (NED), with 80% being M0 intermediate-high-risk patients (any grade, pT3N0M0). However, it remains unclear which M0 intermediate-high-risk patients are most likely to benefit from pembrolizumab adjuvant therapy to maximally reduce recurrence risk. An EAU24 study (Abstract P143) [3] analyzed recurrence risk factors among M0 intermediate-high-risk patients in the KEYNOTE-564 study. Multivariate analysis indicated that age ≥68 years (HR 2.87; P<0.026) and necrosis (HR 3.28; P<0.038) were independent predictors of recurrence risk. Additionally, age ≥68 years (24.46 months vs. 97.54 months, P=0.017) and necrosis (24.43 months vs. 317.5 months, P=0.023) were associated with shorter DFS.

Oncology Frontier: Cytoreductive nephrectomy (CN) is a debated topic in metastatic renal cell carcinoma (mRCC), especially regarding the timing and approach. Could you share your perspective on CN, considering recent studies and updates from EAU24?

Professor Qiang Wei: Cytoreductive nephrectomy (CN) remains controversial. The primary contention stems from the phase III non-inferiority CARMENA study [4], which showed no significant difference in OS between the sunitinib-alone group and the sunitinib-plus-CN group (HR 0.97). Similarly, the phase III SURTIME study [5] addressed the timing of CN, showing that 28-week progression-free survival (PFS) rates were 42% and 42.9% for the immediate CN group (CN before targeted therapy) and the delayed CN group (CN after targeted therapy), respectively. Consequently, the EAU guidelines do not recommend CN for MSKCC high-risk patients and do not advocate immediate CN for asymptomatic MSKCC intermediate-risk patients requiring VEGFR inhibitor therapy.

However, it is crucial to note that both CARMENA and SURTIME studies were conducted during the targeted therapy era. With the advent of the immunotherapy era, does the role of CN change? An EAU24 study from Italy and the USA [6] included 3,138 mRCC patients receiving immunotherapy, with 1,597 (51%) undergoing CN. Comparative analysis with a matched cohort revealed that the 3-year cancer-specific mortality (CSM) was significantly lower in the CN group (54.1%) than in the non-surgical group (80.3%) (P<0.001). Subgroup analysis showed higher CSM for non-surgical patients with one (84.5% vs. 70.0%) or two metastatic sites (87.8% vs. 73.4%) (both P<0.001), whereas no significant difference was observed in patients with ≥3 metastatic sites (89.1% vs. 86.8%).

Another multicenter French study (Abstract A0841) [7] included 102 patients undergoing delayed CN after immunotherapy for mRCC. Although a high proportion (65.7%) of patients reported surgical difficulties, especially for partial nephrectomy (85%), this did not increase the complication rate (30-day postoperative complication rate 22.5%). Moreover, the overall conversion rate to radical surgery reached 15%, and nearly half (48%) of the patients ceased systemic therapy after two years, with 2-year PFS and OS rates of 63% and 85.9%, respectively.

From these EAU24 studies, it appears that CN remains valuable in the immunotherapy era, especially for patients with oligometastasis (1-2 sites), while no benefit is observed for those with extensive metastasis (≥3 sites). Regarding timing, delayed CN remains feasible, with a significant portion of patients achieving R0 resection conversion following systemic therapy.

Oncology Frontier: For mRCC patients, cytoreductive nephrectomy typically involves radical nephrectomy post-systemic therapy. Is nephron-sparing surgery (NSS) feasible for patients eligible for partial resection?

Professor Qiang Wei: In the era of immunotherapy and targeted therapy, CN following systemic therapy can offer benefits, including extending survival and improving tumor response rates. Some patients may achieve the goal of radical surgery through CN. However, whether to opt for radical nephrectomy or nephron-sparing surgery (NSS) for specific patients remains debated. Theoretically, for patients achieving tumor downstaging, NSS is feasible, particularly for those with compromised renal function (e.g., solitary kidney). However, the complexity and risk of surgery must be further evaluated. Therefore, prospective studies are necessary to explore the surgical approaches for delayed CN following systemic therapy.

An EAU24 study from France (Abstract A0832) [8] retrospectively analyzed 13 patients undergoing NSS post-immunotherapy between January 2019 and September 2023. Post-surgery, 10 patients (77%) discontinued immunotherapy, with a median follow-up of 8.4 months and an OS rate of 90%, a median treatment-free survival of 12.9 months, and a 12-month recurrence-free survival rate of 84.6%. This small-sample study suggests that delayed CN with NSS is feasible for downstaged patients post-immunotherapy. Long-term randomized controlled trials are needed to confirm functional and oncological outcomes.

Oncology Frontier: Could you share your center’s experience with robot-assisted radical nephrectomy, particularly for special locations, complex partial nephrectomy, and cases involving venous tumor thrombus?

Professor Qiang Wei: Robot-assisted surgery has gained widespread use in urological oncology, with renal cancer being a major indication. This includes complex cases like special locations (near the renal hilum), multiple tumors, and radical resection involving venous tumor thrombus. Since introducing the da Vinci Surgical System in 2015, West China Hospital has completed over 7,000 robot-assisted surgeries, with approximately one-third for renal cancer, benefiting many patients.

Professor Qiang Wei

Director, West China Urological Disease Center, Sichuan University
Director, Department of Urology, West China Hospital
Professor, Doctoral Supervisor
Vice Chairman, Chinese Urological Association
Vice President, Chinese Medical Doctor Association Urology Branch
Vice Chairman, Male Reproductive Oncology Committee, Chinese Anti-Cancer Association
Vice Chairman, Prostate Cancer and Kidney Cancer Committees, Chinese Society of Clinical Oncology (CSCO)
Director, Sichuan Provincial Clinical Research Center for Kidney and Urological Diseases
President, Sichuan Provincial Robotic Surgery Association
Chairman, Urogenital Oncology Committee, Sichuan Anti-Cancer Association
Chairman, Urology Branch, Chengdu Medical Association

Post Views: 1,093