Wilms Tumor

Hello, I'm Andrew Davidov, chairman of surgery at St. Jude Children's Research Hospital and today we're going to review the essentials of Wilms tumor. Have you ever asked? What exactly is Wilms tumor? Wilms tumor is the second most common intra abdominal tumor in children and fifth most common tumor in children overall. Approximately 75% of the cases occur in children younger than five years of age with a peak incidence at two to three years of age. Thankfully, survival for patients with Wilms tumor, when considered as a whole, is currently greater than 90%. However, a critical prognostic factor that profoundly impacts outcome is histology. This is divided simply into two broad types, favorable and unfavorable or anaplastic histology. The latter group comprises, thankfully, only about 10% of cases, but does contribute to over 50% of Wilms tumor mortality. How do these patients typically present? Well, interestingly, children with Wilms tumor typically present with an asymptomatic abdominal mass. Associated signs and symptoms such as malaise, pain, microscopic or gross hematuria are found in only about 25% of the children, as is hypertension. So if a patient presents with an abdominal mass and you suspect Wilms, what's the typical workup? The workup of a child with an intra abdominal mass that you suspect of being a Wilms tumor usually begins with ultrasound. CT of the abdomen and pelvis is generally the definitive imaging study of choice for those patients who are suspected of having a renal tumor based on ultrasound. CT will confirm the presence of a solid renal mass and will also afford the opportunity to visualize the contralateral kidney to confirm its presence and function and to exclude synchronous bilateral disease. Intravascular tumor extension occurs in about 6% of Wilms tumor cases, therefore this should be specifically investigated in preoperative evaluation as it may alter the timing and conduct of surgery. If intracardiac extension of tumor thrombus is suspected, this can be assessed by echocardiography. The most common site of metastatic spread of Wilms tumor is the lungs, and so a chest CT should be included in the initial evaluation of a child suspected of having Wilms tumor. Quick pause, how do you stage a patient with Wilms tumor? The Children's Oncology Group currently uses a surgical pathologic staging system in which localized Wilms tumors that are confined within the renal capsule are stage one, while those that penetrate the renal capsule but are resected with negative margins are stage two. Circumstances that make Wilms tumor stage three are various and include biopsy or rupture, either pre-operative or intraoperative, positive resection margin or gross residual disease, lymph node involvement, or administration of preoperative chemotherapy. Metastatic disease, which occurs in about 12% of patients, is considered stage four, although the local stage should also be evaluated, as this will determine whether abdominal radiation is indicated and to what field. Patients with synchronous bilateral Wilms tumor are stage five, but here again, local stage for each side should still be evaluated. Time for some management decisions. What would you do for a four-year-old with a unilateral Wilms tumor? For unilateral tumors, up-front resection with regional lymph node sampling is currently the recommendation from the Children's Oncology Group, and by up-front resection that's generally radical nephrectomy. And the reason why this approach is favored by the cog is twofold. First, although Wilms tumors can grow to a large size, even large tumors rarely invade surrounding structures. And so because of this, most Wilms tumors are resectable at presentation. Secondly, uh the failure to perform an up-front resection, but instead administering neoadjuvant chemotherapy, in the cog results in the classification of a tumor as stage three, thus mandating the use of other therapies including flank radiation and doxorubicin, each of which is associated with significant long-term toxicities. Treatment of favorable histology Wilms tumor that's stage one or two is just limited to vincristin and actinomycin D. And more recently, in rare circumstances when the tumor is stage one, weighs less than 550 grams, that's the tumor weight plus the kidney, and the patient is less than 2 years of age, no advent chemotherapy is given. And actually, raising the age and the weight limits of the tumor plus kidney are currently being considered for study by cog. But it is important that careful lymph node sampling be done, as it's a critical part of any operation for Wilms tumor because the presence of nodal involvement is associated with an increased incidence of tumor relapse and a poorer prognosis, although effective, albeit more intensive therapy exists to treat children with stage three disease. So lymph node sampling should be performed even in the absence of abnormal nodes on pre-operative imaging or on gross inspection during operative exploration, since these circumstances really don't reliably predict lymph node negativity. Partial nephrectomy for patients with unilateral, non-syndromic disease and or laparoscopic nephrectomy are really not currently standard of care and should generally only be performed in the context of a clinical trial. What if that four-year-old had bilateral Wilms tumors? What would you do then? So about 5% of children with Wilms tumor will present with synchronous bilateral disease or stage five disease. And in these circumstances, due to an increased risk of renal failure for these patients, they receive neoadjuvant chemotherapy with three drugs as used for patients with stage three or stage four favorable histology Wilms tumor. in an effort to shrink the tumors prior to surgery and to facilitate the preservation of of normal renal parenchyma. Also treated in this manner are patients with Wilms tumor arising in a solitary kidney or as I mentioned before, those with unilateral Wilms tumor who are an increased risk for developing metachronous tumor, although these patients usually don't receive doxorubicin as part of their neoadjuvant chemotherapy. A biopsy is not required in children with bilateral solid renal masses, as bilateral Wilms tumor is the very likely diagnosis, although the histologic subtype, favorable or unfavorable, won't be known. Uh studies have shown that biopsies of bilateral renal masses rarely detect anaplasia even when it does exist in the tumor mass. However, a biopsy if performed doesn't mandate subsequent radiation as it does in patients with unilateral Wilms tumor. Bilateral nephron sparing surgery should really be considered in all patients with bilateral Wilms tumor. This should be performed after either six or 12 weeks of neoadjuvant chemotherapy. Longer courses of pre-operative chemotherapy are definitely discouraged. Okay, back to unilateral Wilms tumor. Now with intravascular extension, how do you manage this patient? So these cases can be quite challenging. It it should be determined by pre-operative imaging that there is or isn't intravascular tumor extension, then its presence or absence confirmed intraoperatively. Tumor extension into the renal vein and and proximal inferior vena cava can in most cases be removed and blocked with the kidney and tumor. Thrombus that extends further into the vena cava can also be withdrawn from the IVC after gaining proximal and distal control. Proximal control can generally be achieved if the superior extent of the thrombus is below the level of the hepatic veins. However, primary resection of tumors with extension above the level of the hepatic veins or especially into the the atrium is associated with higher operative morbidity and so neo-adven chemotherapy is generally used in these circumstances. Thrombus that extends above the hepatic veins and which persists to this extent after neoadjuvant chemotherapy probably requires cardiopulmonary bypass to safely remove the full extent of disease. Now for our final case, what if our initial four-year-old with a unilateral Wilms tumor had metastasis at the initial evaluation? About 12% of Wilms tumor patients will have evidence of hematogenous metastasis at diagnosis with 80% of these being pulmonary metastasis. Interestingly, a new response-based approach is being used for the patients with stage four disease in the Children's Oncology Group. These patients treated with three drug chemotherapy who have radiographic disappearance of their lung metastasis or who have tissue confirmation that residual nodules don't contain viable tumor at week six imaging re-evaluation will be considered rapid responders. will continue on this three drug chemotherapy at six weeks will be considered slow or incomplete responders. They will be switched to more intensive chemotherapy regimen and will receive whole lung radiation. Now that you've reviewed the lecture, what would you say are your key clinical takeaways? Here were our key takeaways that we hope you can apply in your practice. Wilms is the most common renal tumor in children. It has an outstanding overall survival at greater than 90%, but that's worse with anaplastic histology. The treatment for unilateral disease is a radical nephrectomy with lymph node sampling, followed by vin Christine and actinomycin B for stages one and two. For stage three, add Doxorubicin and radiation therapy. For bilateral disease, neoadjuvant three drug therapy, and then nephron sparing surgery, if possible, is the way to go. If there's intravascular involvement, the approach is based on the extent of the tumor. If it's above the hepatic veins, give neoadjuvant chemotherapy. And for lung metastasis, management is now response-based to avoid pulmonary radiation. You made it through Wilms tumor. Congratulations. Now let us know what you thought, what you liked, what you didn't, and what you'd like to see in the future. This videocast was created and edited by Ray Hanky, Zach Corb, Todd Ponky, and the rest of the St. Curt crew.