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.