Surgery-related factors and local recurrence of Wilms tumor in National Wilms Tumor study 4

Objective To assess the prognostic factors for local recurrence in Wilms tu mor. Summary Background Data Current therapy for Wilms tumor has evolved through four studies of the National Wilms Tumor Study Group. As adverse prognosti c factors were identified, treatment of children with Wilms tumor has been tailored based on these factors. Two- year relapse;free survival of childre n in the fourth study (NWTS-4) exceeded 91%. Factors once of prognostic imp ort for local recurrence may lose their significance as more effective ther apeutic regimens are devised. Methods Children evaluated were drawn from the records of NWTS-4. A total o f 2482 randomized or followed patients were identified. Local recurrence, d efined as recurrence in the original tumor bed, retroperitoneum, or within the abdominal cavity or pelvis, occurred in 100 children. Using a nested ca se-control study design, 182 matched controls were selected. Factors were a nalyzed for their association with local failure. Relative risks and 95% co nfidence intervals were calculated, taking into account the matching. Results The largest relative risks for local recurrence were observed in pa tients with stage III disease, those with unfavorable histology (especially diffuse anaplasia), and those reported to have tumor spillage during surge ry. Multiple regression analysis adjusting for the combined effects of hist ology, lymph node involvement, and age revealed that tumor spillage remaine d significant. The relative risk of local recurrence from spill was largest in children with stage II disease. The absence of lymph node biopsy was al so associated with an increased relative risk of recurrence, which was larg est in children with Stage I disease. The survival of children after local recurrence is poor, with an average survival rate at 2 years after;relapse of 43%. Survival was dependent on initial stage: those who received more th erapy before relapse had a worse prognosis. Conclusions This study has demonstrated that surgical rupture of the tumor must be prevented by the surgeon, because spills produce an increased risk of local relapse. Both local and diffuse spills produce this risk. Stage II children with local spill appear to require more aggressive therapy than t hat used in NWTS-4. The continued critical importance of lymph node samplin g in conjunction with nephrectomy for Wilms tumor is also established. Abse nce of lymph node biopsy may result in understaging and inadequate treatmen t of the child and may produce an increased risk of local recurrence.