For patients with limited and locally progressive renal cell carcinoma, surgery remains the treatment of choice as a potentially curative option. In patients with elective advanced renal cell carcinoma, if the patient is able to tolerate surgery, reduction nephrectomy and isolated metastasis resection in addition to systemic therapy may also improve patient survival.
1.

RN

In 1963, Robson et al established the basic principles of RN and established it as the gold standard for the surgical management of limited renal cell carcinoma. The classic scope of RN resection included the affected kidney, perirenal fascia, perirenal fat, ipsilateral adrenal glands, lymph nodes from the foot of the diaphragm to the abdominal aortic bifurcation, and the ureter above the iliac vessel bifurcation. Current concepts have changed and intraoperative adrenalectomy and regional lymph node dissection are not routinely recommended.
2.

Kidney unit preservation surgery

Patients left with only one kidney after RN may have decreased renal function and increased risk of chronic renal insufficiency and dialysis. Chronic renal insufficiency increases the patient’s risk of cardiovascular events and increases overall mortality. For patients with limited renal cell carcinoma, nephron sparing surgery (NSS) is recommended for patients with clinical stage T1a renal cell carcinoma, if technically feasible. The thickness of the normal renal parenchyma surrounding the tumor to be removed is not a critical issue, as long as the final surgical specimen has negative margins. Although there is an increased risk of local tumor recurrence after partial nephrectomy, the patient-specific mortality rate is similar to that of RN. The location of the tumor (exophytic or endophytic) is more important than the size of the tumor for the feasibility of partial nephrectomy. A tumor that is too large or too deeply located increases the time of thermal ischemia during renal surgery and the risk of complications from postoperative bleeding and urinary leakage is increased. Therefore, the indication for NSS also depends to some extent on the experience and surgical skill of the surgeon.
3.

Surgery-related issues

(1)

Open surgery / laparoscopic surgery / robot-assisted technology

: Compared with traditional open surgery, the advantages of laparoscopic surgery are small surgical incision, less injury, less bleeding, faster postoperative recovery, fewer comorbidities, shorter hospital stay, and no significant difference in recent tumor control rate compared with open surgery. The disadvantages are expensive instruments, more complex technique, longer learning curve for proficiency, and longer operative time in the initial stage. As the technique becomes more proficient, the operative time will be significantly reduced and the degree of complete resection will be exactly the same as that of open surgery. The introduction of the da Vinci robot has made several key steps of laparoscopic partial nephrectomy easier to master and the learning curve faster. Currently, open surgery, laparoscopic surgery, or robotic-assisted techniques can be used for the surgical treatment of patients with renal cell carcinoma when technically possible, and the choice depends largely on the size and location of the renal tumor and the surgeon’s level of experience.
(2)

Ipsilateral adrenalectomy

: The classic scope of RN includes the ipsilateral adrenal gland. However, given the low risk of ipsilateral adrenal involvement in smaller renal cell carcinomas, intraoperative preservation of the ipsilateral adrenal gland should be considered in the absence of an abnormal adrenal gland on CT scan. If ipsilateral adrenal abnormalities are found during surgery, they should be removed.
(3)

Regional lymph node dissection

(3)

Regional lymph node dissection

: The need for regional retroperitoneal lymph node dissection in the setting of RN is also controversial. There is no evidence that lymph node dissection is beneficial to patients. The European organization for research and treatment of cancer (EORTC) 20-year randomized controlled phase III clinical study showed that lymph node dissection for resectable limited renal cell carcinoma (N0M0) versus no lymph node dissection was associated with a higher rate of progression-free survival, time to disease progression, and overall survival in both groups. The differences in time to disease progression and overall survival rates were not statistically significant. Therefore, regional or extensive lymph node dissection is generally not routinely performed in patients with renal cell carcinoma undergoing RN. If preoperative imaging shows regional lymph node enlargement or swollen lymph nodes are palpated intraoperatively, regional lymph node dissection or resection is feasible to clarify the pathological stage.
(4)

Management of positive tumor margins

: The most important concern of partial nephrectomy patients is the recurrence of tumor. The rate of ipsilateral renal tumor recurrence after partial nephrectomy is ∼1-6, mostly due to multifocal or positive cut margins of the primary renal cell carcinoma. Whether positive surgical margins in partial nephrectomy increase the risk of tumor recurrence and the prognostic impact of partial nephrectomy remains controversial. Studies have shown that even with positive margins for partial nephrectomy, there is no increase in tumor recurrence at midterm follow-up. Even some studies have shown that the majority of patients who underwent remedial nephrectomy immediately after surgery or later did not show signs of tumor residual. The literature reports positive postoperative pathological margins in ∼3-8 NSS, but only those patients with higher pathological grading (grade III-IV) are at increased risk of postoperative recurrence.
(5)

Management of venous tumor thrombosis

Approximately 10 of patients with renal cell carcinoma are associated with renal or inferior vena cava aneurysms, and the grading of venous aneurysms in renal cell carcinoma is often based on the five-level classification of the Mayo Medical Center (Table 8). Because of the risks and complications associated with surgical treatment of venous aneurysms, preoperative evaluation requires thorough preparation, a detailed treatment plan, and an experienced team to perform the procedure.

Evaluation

: A preoperative enhanced MRI or CT scan and angiography is performed to understand the extent and degree of venous aneurysm emboli and the presence of venous wall invasion in order to develop a plan for further surgical treatment.

Surgery

: The surgical approach to locally advanced renal cell carcinoma with venous thrombosis varies depending on the extent of the venous thrombosis. The first step of surgery is to separate the vessels. The renal artery on the tumor side is ligated at the root of the aorta, followed by control of the vein and removal of the aneurysmal embolus. For better control of bleeding and tumor exposure, branch vessels of the inferior vena cava (lumbar veins, small branches of hepatic veins, etc.) can be ligated. It is important not to ligate all the branches in order to ensure smooth venous return. The kidney and the tumor should be touched as little as possible during the operation to reduce the risk of dislodging the tumor embolus. Surgery for a neoplastic thrombus confined to the renal vein or a neoplastic thrombus that has just entered the inferior vena cava is similar to a routine radical nephrectomy. When the thrombus is between the opening of the renal vein and the hepatic vein, the inferior vena cava is blocked above and below the thrombus, and the contralateral renal vein needs to be blocked. Usually, a blood shunt technique is not required. The vessel is incised anterior to the inferior vena cava and the kidney and tumor, the ipsilateral renal vein, and the aneurysmal vein are removed together. The lining of the inferior vena cava is carefully inspected and flushed to avoid residual tumor. When the tumor embolus is between the hepatic vein and the diaphragm, a blood shunt technique is required, and the decision to use this technique is based on the degree of inferior vena cava blockage required during the procedure and the hemodynamic alterations caused.

Prognosis

: The relationship between the degree of venous aneurysm embolism and survival prognosis is not clearly established. A retrospective study including 422 cases showed that patients with inferior vena cava aneurysms had a worse survival prognosis than those with aneurysms confined to the renal veins. Blute et al. reported a median survival time of 3.1 years and a 5-year survival rate of 59% in patients with venous aneurysmal renal cell carcinoma without distant metastases or lymph node metastases and without postoperative adjuvant therapy.
Table 8 Mayo clinical classification of tumor thrombosis five-level classification(6)

Management of stage T4 renal cell carcinoma

(6) Stage T4 renal cell carcinoma: When renal cell carcinoma invades beyond the renal fascia and involves surrounding organs, it is a stage T4 tumor. It may involve the ascending colon, duodenum, descending colon, pancreas, diaphragm, liver, spleen, adrenal glands, ureter, etc. Early studies have shown that stage T4 tumors have poor surgical outcome and surgical treatment is not recommended. The MDACC study reported that 30 patients with preoperative clinical stage T4NxM0 underwent surgery, and the tumor and adjacent organs invaded were resected intraoperatively with negative margins.
The staging of 60 patients showed a downstaging, including 2 patients with T2 stage pathology. Multifactorial regression analysis showed that pT4 and lymph node metastasis were independent predictors of survival prognosis. The 3-year overall survival rate was 66 for patients with negative lymph nodes and 12 for patients with lymph node metastasis. This study suggests that preoperative and intraoperative staging is not entirely accurate and that a significant number of patients have overestimated staging. The MSKCC study reported that in patients with renal cell carcinoma with stage T3 or T4 pathology combined with adjacent organ resection, approximately 1 in 4 patients had lymph node metastases, and the majority of patients had negative margins (36 positive margins). The survival time of patients with positive margins was significantly shorter. The median survival time for the entire group was 11.7 months.Capitanio retrospectively analyzed the SEER database of renal cell carcinoma with clinical stage T4N0 to 2M0, 246 patients who underwent surgery and 64 patients who did not. The median survival time for patients in the operated group was 48 months, compared with 6 months for patients in the non-operated group. The 10-year tumor-specific mortality rate for the 125 patients in the surgical group with pathologic stage T4N0 was 40. However, no significant benefit was seen in patients with lymph node metastases. Multidisciplinary collaboration is important in the management of patients with clinical stage T4 renal cell carcinoma, as it involves the resection and reconstruction of adjacent organs. In conclusion, aggressive surgery in patients with clinical T4N0M0 renal cell carcinoma may provide significant benefit if conditions permit.