Operative phase
The panel suggests neoadjuvant chemotherapy for the treatment of patients with the typical clinical features of WT. (Weak recommendation; Quality of evidence: Moderate; Table 3)
Panel deliberation. Neoadjuvant chemotherapy goals are to decrease tumor size, prevent tumor spillage, and risk-stratify postoperative treatment based on tumor response. Neoadjuvant chemotherapy is also associated with lowering the incidence of tumor spillage and decreasing the stage of the disease.31-33This may be particularly relevant in limited-resource settings, where tumor stage at diagnosis is mostly advanced, and therapy intensification is challenging because of barriers to accessing radiation therapy and supportive care. In some settings, upfront surgical resection is considered a measure to adapt to issues related to chemotherapy supply chain and accessibility. In these cases, surgical resection is performed at the time of diagnosis at the reference center, followed by chemotherapy close to the patient’s residence. Upfront resection may prevent the administration of inappropriate therapy in a small percentage of patients and may help select patients with very low–risk WT who can be treated with surgery alone. However, a surgery-only approach is more appropriate in the context of advanced diagnostic capacity supporting molecular and genomic tumor analysis.34,35
The panel suggests adequate trans-peritoneal laparotomy incision for resection of WT. (Weak recommendation; Quality of evidence: Very Low; Table 4)
Panel deliberation. WT surgical oncology principles include optimal visualization of vital anatomical structures to avoid injury, minimal tumor handling to prevent tumor spillage, and adequate surgical staging, particularly with lymph node sampling. Minimally invasive surgery is an attractive approach for treating small tumors; however, it should not compromise staging, lymph node sampling, or prevention of tumor capsule injury.36-39
The panel recommends adequate and documented surgical staging for the management of WT. (Strong recommendation; Quality of evidence: Very Low)
Panel deliberation. Postsurgical therapy relies on pathologic staging and surgical staging. In some scenarios, especially in the context of limited diagnostic capacity, documented surgical findings may be the only indicator of tumor spillage. Failure to perform lymph node sampling results in suboptimal tumor staging. This may lead to inadequate therapy or, conversely, to overtreatment with associated potential toxicities. Adequately documented surgical staging should include lymph node sampling and documentation of local invasion, seeding or tumor spillage, and vascular extension (Supplemental Table S3).28,40-45
The panel recommends sampling of lymph nodes at the time of resection of WT; pathologic assessment of lymph node histology before and after chemotherapy is feasible and of value in staging. (Strong recommendation; Quality of evidence: Very Low)
Panel deliberation. Determining lymph node involvement by histology is feasible both before and after neoadjuvant chemotherapy.46 Lymph node sampling is an integral part of staging and should be completed at the time of tumor resection, regardless of whether neoadjuvant chemotherapy was given.28,40-45 At the time of sampling, five to seven lymph nodes should be obtained to reduce the risk of a false-negative finding.41,44
The panel recommends neoadjuvant chemotherapy for the management of WT with inferior vena cava thrombus extension. (Strong recommendation; Quality of evidence: Very Low; Table 5)
Panel deliberation. Neoadjuvant chemotherapy is associated with the mitigation of complications during the surgical resection of WT with tumor thrombus in the inferior vena cava. Also, the need for cardiopulmonary bypass may be reduced in patients with pretreated supra-diaphragmatic vena cava thrombus.19,47-50Neoadjuvant chemotherapy should be used in all patients with WT and tumor thrombus in the inferior vena cava; this is particularly relevant in limited-resource settings.
The panel recommends evaluating the presence of viable tumor cells within the thrombus for patients with WT and inferior vena cava extension. (Strong recommendation; Quality of evidence: Very Low)
Panel deliberation. Up to two thirds of tumor thrombi include viable tumor cells.51,52 Viable tumor thrombus in the context of incomplete macroscopic resection increases the risk of WT relapse and death.51,52 When complete gross resection of the tumor thrombus is achieved, the viability of the thrombus may be considered in determining the need for radiation therapy.
The panel recommends neoadjuvant chemotherapy followed by en bloc surgical resection of WT with the inferior vena cava thrombus extension. (Strong recommendation; Quality of evidence: Very Low)
Panel deliberation. Intravascular tumor extension increases the complexity of surgical resection and is associated with an increased risk of bleeding and other complications; however, resection is an integral part of the local control strategy of tumor thrombus. Complete resection of the tumor thrombus should be the goal of surgery whenever possible.51,52 WT with inferior vena cava extension should be managed in a referral center. Extending neoadjuvant therapy beyond 6 weeks is not associated with improved surgical resection, further thrombus regression, or survival advantage.53
The panel recommends neoadjuvant chemotherapy for 6 to 12 weeks for patients with bilateral WT requiring nephron-sparing resection.(Strong recommendation; Quality of evidence: Very Low)
Panel deliberation. Tumor response to chemotherapy should be assessed at 6 weeks and 12 weeks; maximal tumor shrinkage occurs within the first 12 weeks of neoadjuvant chemotherapy.54 Tumors that show no response to chemotherapy after 6 weeks should be resected to prevent the side effects of protracted chemotherapy. Protracted chemotherapy may subject patients with stromal-type tumor to unnecessary toxicities or delay appropriate therapy for patients with anaplasia.
The panel suggests not to routinely use complex hilar techniques, including continuous vascular clamping and bench surgery, for bleeding control in patients with bilateral WT requiring nephron-sparing resection. (Weak recommendation; Quality of evidence: Very Low)
Panel deliberation. Large series have demonstrated that nephron-sparing surgery can be successfully completed using intermittent manual compression.55,56 However, selected patients may require more complex hilar control maneuvers. Surgeons should avoid prolonged ischemia (more than 20 min)57,58 of the residual renal tissue, as it is associated with adverse outcome of renal function.
The panel suggests intraoperative histologic confirmation of uncertain margins in patients with WT requiring nephron-sparing resection.(Weak recommendation; Quality of evidence: Very Low)
Panel deliberation. Intraoperative margin biopsy should be considered for areas of uncertain margins and potential residual disease. Frozen sections, however, are not needed routinely, especially when the tumor was resected with either a margin of normal renal parenchyma or an intact capsule.
The panel suggests that nephron-sparing resection not be performed in patients with unilateral WT. (Weak recommendation; Quality of evidence: Very Low; Table 6)
Panel deliberation. Nephron-sparing surgery for unilateral WT may be associated with increased risk of tumor spillage and is not the standard of care.59-63 Nephron-sparing surgery may be feasible, especially in small polar tumors; however, the primary priority is to achieve complete tumor resection with negative margins. Nephrectomy for unilateral WT is associated with high overall survival and high recurrence-free survival, with an extremely low incidence of renal failure in patients who do not have cancer-predisposition syndrome. Nephron-sparing surgery is indicated primarily for patients with unilateral WT in the context of cancer-predisposition syndrome or for those who have only one kidney.