What should the adult urologist know about pediatric urologic cancers?

Introduction

Fortunately for patients and families, pediatric urologic oncology is a relatively small component of both pediatric urology and pediatric oncology practice. Despite the rarity of these diagnoses, there is an important role that both the pediatric and adult urologist can play in the management of kidney,

bladder/prostate, and testicular cancers in the pediatric, adolescent, and young adult (AYA) populations. In particular, AYAs often have malignancies with overlapping childhood and adult urologic management strategies that urologists are uniquely positioned to navigate.

Since most solid tumors of the genitourinary organs are rare in children, the creation of large cooperative groups (Children’s Oncology Group [COG] in North America and Société Internationale d’Oncologie Pédiatrique [International Society of Pediatric Oncology; SIOP] for most European countries) has allowed for the study and propagation of evidence-based treatment guidelines through multi-institutional collaboration. Unfortunately, there is evidence that despite vast improvements in overall survival, AYAs are at risk for worse cancer-specific outcomes.^1,2 This may be related to socioeconomic factors, tumor biology, or treating physician unfamiliarity with established protocols for pediatric-type tumors that present in older patients.

Kidney Masses

The most common renal malignancy in children is Wilms tumor (WT). However, once patients reach 11 years of age, renal cell carcinoma (RCC) becomes the most likely renal malignancy.³ Yet, WT can present later in life and 3% will present in adults.⁴ Key concepts in the management of suspected WT include avoiding biopsy unless in the context of a multidisciplinary discussion; up-front radical nephrectomy except for special circumstances (eg, genetic predisposition syndromes, solitary kidney, bilateral tumors); and lymph node

(LN) sampling to assure adequate staging. Having a preoperative biopsy or positive LNs will typically result in therapy intensification to include radiation therapy and cardiotoxic doxorubicin, both of which contribute to long-term morbidity.

Since adult urologists are more familiar with the management of RCC, there is a natural opportunity to increase adult urology involvement in older children and AYAs with renal masses. The most common histologic subtype of RCC in younger patients is translocation RCC (tRCC).⁵ This RCC subtype is associated with a TFE gene rearrangement, and it is known to be more aggressive. It can also be seen as a secondary malignancy in patients with a history of cytotoxic chemotherapy. Up to 50% of patients have LN involvement regardless of imaging appearance, even with tumors smaller than 4 cm.³ Surgical recommendations are generally the same as for WT (radical nephrectomy with RP LN sampling, although use of partial nephrectomy and/or laparoscopy is common in smaller lesions amenable to these approaches). Unfortunately, AYA patients are less likely to have LN sampling at the time of surgery, likely secondary to the unfamiliarity of treating surgeons with pediatric surgical guidelines.⁶ There is also some evidence that complete surgical resection, including involved LNs, may confer a survival advantage in tRCC.⁷

Broadly speaking, urologists evaluating AYAs with solid renal masses should keep both tRCC and WT in the differential and consider the impact that presurgical evaluation (biopsy) and intraoperative decision-making (LN sampling) may confer to adjuvant therapy and survival.

Bladder/Prostate Masses

Most cancers of the bladder and prostate (B/P) in children are rhabdomyosarcoma (RMS), but there are rare cases of urothelial carcinomas, often associated with Lynch syndrome. The treatment algorithm for B/P RMS is complex, but in the modern era, it relies heavily on multimodal therapies. Initial diagnosis relies on biopsy vs complete resection, the latter being rarely possible up front without significant morbidity. Chemotherapy is then started, followed by local control strategies. Surgery and radiation are both considered forms of local control, which are added after induction chemotherapy. Surgery as the primary form of local control is typically limited to cases where complete resection is possible while also maintaining organ function, or for refractory disease. In select cases, complete surgical resection can eliminate or reduce the need for radiation therapy depending on the timing of surgery in relation to the initiation of chemotherapy, a concept known as pretreatment re-excision (complete resection before chemotherapy; eliminate radiation) or delayed primary excision (complete resection after chemotherapy; reduce dose of radiation).

One of the primary prognostic indicators for RMS is tumor fusion status, which refers to a chromosomal translocation between either PAX3 or PAX7 and FOXO1 genes. Fusion-positive tumors portend worse survival and are responsible for the poor outcomes classically associated with alveolar histology.⁸

Urothelial cancers in younger patients tend to be solitary, superficial, low grade, and low stage with overall low short-term mortality and recurrence rates.⁹ Unlike adult patients with urothelial carcinoma, no formal surveillance recommendations exist.

Testicular/Paratesticular Masses

The initial evaluation of a solid, para-, or testicular mass in children mirrors that for adult patients—begin with a scrotal ultrasound and tumor markers. For testis masses, pubertal status, not patient age, will provide the basis for medical decision-making. Solid testicular masses in postpubertal male patients are more likely to represent malignancy, whereas prepubertal patients are more likely to have benign masses (teratoma). The most common malignant tumor in children is yolk sac tumors, the majority (90%) of which are stage I with an elevated α-fetoprotein (AFP).¹⁰ Prepubertal boys with normal serum tumor markers are appropriate for partial orchiectomy. Importantly, AFP is normally elevated in infants and therefore needs to be interpreted with caution in infants less than 6 months of age.¹¹ Intraoperative frozen section is then a reliable way to determine the need to complete a radical orchiectomy under the same anesthetic.¹² Postpubertal male patients should be treated per adult guidelines, regardless of age or stage, and teratoma is considered malignant in this group. Because adult urologists typically have more experience with retroperitoneal LN dissection and its indications, these cases are excellent opportunities for surgical collaboration. Solid paratesticular masses should be treated with radical orchiectomy (inguinal incision) due to concern for RMS. Ipsilateral RP LN sampling is required in all children with paratesticular RMS who have clinically involved nodes, are over 10 years of age, or who have fusion-positive tumors. The sampling template is akin to that for testicular cancer, and the goal LN yield is 7 to 12.¹³ (Table)

Cooperative Trials and Research Opportunities

Outside the realm of clinical care, there are also several research endeavors available to patients who may receive their care primarily through an adult urology or medical oncology clinic. These include National Cancer Institute–sponsored combined COG studies AGCT1531 and 1532, which are phase 3 trials for low-, intermediate-, and poor-risk patients with testicular germ cell tumors, up to 50 years of age. Most pediatric-type diagnoses (WT, RMS) have associated trials that encourage enrollment up to age 30.

The recently opened COG favorable histology WT trial, AREN2231, includes patients up to 30 years of age. Study goals include expanding the use of nephrectomy-only treatment for stage I disease as well as introducing novel deintensified adjuvant chemotherapy regimens for those patients with favorable genomic markers.

Patients who receive a diagnosis of tRCC can now also participate in The Count Me In Translocation Renal Cell Carcinoma Project, a patient self-enrollment project aimed at building a data repository of clinical and molecular information for use in research of this rare malignancy.¹⁴

The International Soft Tissue Sarcoma Consortium has multiple guidelines on soft tissue sarcomas relevant to patients of all ages. This is a data commons that allows combined analysis of SIOP and COG data, accounting for differences in approaches.

Survivorship

Unlike many adult patients with urologic cancers, long-term survival is common for children decades after their initial diagnosis and treatment, and late effects due to therapy are well documented.¹⁵ Gonadotoxic treatments are common, and fertility preservation should be at the forefront of a treating physician’s mind prior to beginning therapy.

Patients with B/P RMS are lifelong urology patients, with bladder issues related to radiation and/or surgery.¹⁶ Secondary malignancies are a very real concern.¹⁷

Pediatric-type cancer diagnoses in adults are rare, and there are important differences in caring for children with genitourinary malignancies compared with adults. No one is expected to know all the nuances across all ages, so it is important to reach out for help when faced with a rare clinical scenario.

REFERENCES

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14. The Count Me In Translocation Renal Cell Carcinoma Project. Accessed June 24, 2025. https://trccproject.org/.

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