Locally progressive renal cell carcinoma is defined as renal cell carcinoma that breaks through the perinephric tegument and involves the perinephric fat or sinus fat but remains confined to the renal fascia, and may be associated with regional lymph node metastases or/and venous tumor emboli without distant metastases. RN is preferred for locally progressive renal cell carcinoma, and partial nephrectomy is performed only in selected patients with technical feasibility and clinical need. Some retrospective or prospective phase II studies have shown that preoperative neoadjuvant targeted therapy for stage T2 to T3 renal cell carcinoma has some shrinking effect and can be tried in cT3 stage tumors that are difficult to be resected locally, but there is a lack of high-level studies to confirm this. In recent years, neoadjuvant therapy with immune checkpoint inhibitors in single or combination regimens has also been widely studied.
The choice of whether to remove regional lymph nodes or angiosarcoma plugs is based on the extent of the lesion and the patient’s physical condition. Lymph node dissection: Regional or expanded lymph node dissection in patients with locally progressive renal cell carcinoma is only relevant to determine the stage of the tumor and does not improve survival in those with negative imaging lymph nodes (cN0). In contrast, lymph node dissection is feasible for patients with positive lymph nodes (cN+), but lymph node dissection is only beneficial for some patients and the extent of dissection is still controversial. (2) Surgical treatment of renal vein or/and vena cava thrombosis: For patients with renal cell carcinoma combined with venous thrombosis without distant metastasis, surgical resection of the affected kidney and thrombosis should be pursued if technically feasible. The length of the renal cell carcinoma venous thrombus and whether the thrombus infiltrates the vena cava wall are closely related to the patient’s prognosis. (3) For patients with preoperative imaging or intraoperative exploration that reveals adrenal tumor, the affected adrenal gland should be removed together.
Adjuvant therapy after surgery for locally progressive renal cell carcinoma: There is no standard adjuvant therapy protocol for locally progressive renal cell carcinoma after surgery, which is firstly recommended to join clinical trials, otherwise given to observation and follow-up. In patients with limited high-risk clear cell renal cell carcinoma, a randomized, double-blind, placebo-controlled phase III clinical study (S-TRAC trial) enrolled 615 high-risk clear cell renal cell carcinomas (stage III-IV and/or regional lymph node metastases) on sunitinib (50 mg/d, 4/2 regimen) or placebo for 1 year. Compared with placebo, adjuvant sunitinib prolonged disease-free survival in patients with limited high-risk renal clear cell carcinoma after surgery (6.8 years vs. 5.6 years, HR 0.76, P=0.03), but failed to improve overall survival, while patients were subject to clear drug-related toxicities and economic burden. Therefore, at this stage only for patients with renal clear cell carcinoma at high risk of recurrence, postoperative adjuvant maintenance of adequate (full dose), adequate (reduced dose interruption), and prolonged (at least 1 year) targeted sunitinib therapy may be an option with full knowledge of the risks and possible benefits associated with adjuvant therapy. The Chinese Expert Consensus (2020) on adjuvant therapy after surgery for high-risk non-metastatic renal cell carcinoma states that the available evidence-based medical evidence does not support adjuvant cytokine therapy after surgery for renal cell carcinoma. Clinical trials of adjuvant immunotherapy with immune checkpoint inhibitors and immune combination targeting after surgery for high-risk non-metastatic renal cell carcinoma are underway and results are expected.