Preoperative chemotherapy and local stage III in nephroblastoma

Abstract

The evolution of Nephroblastoma (WT) treatment over the last decades has been one major success around the world. Despite pursuing different upfront treatment approaches the Children's Oncology Group (COG, former National Wilms Tumor Study Group, NWTSG) and the International Society of Paediatric Oncology's Renal Tumor Study Group (SIOP-RTSG) show the same outcome. Treatment starts with preoperative chemotherapy in SIOP-RTSG compared to initial surgery in COG. Response to chemotherapy can be used as a stratification parameter. This allows treating patients with blastemal subtype more aggressively resulting in a better event free survival (EFS). Moreover the percentage of patients with local stage III is less in SIOP-RTSG than in COG studies. Lymph node involvement, in NWTS 5 together with residual microscopic disease, results in a lower EFS in both study groups. But overall survival (OS) is not different comparing patients with or without positive lymph nodes (LN). No other reason for stage III has a significant impact on outcome. The role of radiotherapy for local tumor control in stage III is important, but the radiation dose needs to be questioned as 10.8 Gy used in COG is as efficient as 15 Gy in SIOP-RTSG protocols. In addition in part of low income countries radiotherapy can not be given due to a lack of radiation facilities. Nevertheless some patients are cured without irradiation. The analysis of local stage III patients underlines the importance of preoperative chemotherapy and the need for molecular studies to better stratify patients according to their individual risk.

Keywords: Nephroblastoma; local stage III; outcome; preoperative chemotherapy.

Figure 1

Tumor volume at the time of diagnosis and after preoperative chemotherapy (n=154) of patients with non-metastatic unilateral Wilms tumor and local stage III treated according to the consecutive SIOP/GPOH trials and studies 9, 93-01 and 2001. The difference is statistically highly significant (P<0.001). Mean tumor volume at diagnosis: 608±436 mL, mean tumor volume after pre-operative chemotherapy: 315±366 mL.

Figure 2

Event free survival (EFS) and overall survival (OS) of patients with non-metastatic unilateral Wilms tumor and local stage III after preoperative chemotherapy treated according to the consecutive SIOP/GPOH trials and studies 9, 93-01 and 2001.

Figure 3

Event free survival (EFS) and overall survival (OS) of patients with non-metastatic unilateral Wilms tumor and local stage III after preoperative chemotherapy treated according to the consecutive SIOP/GPOH trials and studies 9, 93-01 and 2001 according to their histology (low + intermediate and high risk).

Figure 4

Event free survival (EFS) and overall survival (OS) of patients with non-metastatic unilateral Wilms tumor and local stage III after preoperative chemotherapy treated according to the consecutive SIOP/GPOH trials and studies 9, 93-01 and 2001. Only patients with high risk histology.

Figure 5

Event free survival (EFS) and overall survival (OS) of patients with non-metastatic unilateral Wilms tumor and local stage III after preoperative chemotherapy treated according to the consecutive SIOP/GPOH trials and studies 9, 93-01 and 2001. Influence of rupture is shown.

Figure 6

Event free survival (EFS) and overall survival (OS) of patients with non-metastatic unilateral Wilms tumor and local stage III after preoperative chemotherapy treated according to the consecutive SIOP/GPOH trials and studies 9, 93-01 and 2001. Influence of resection R0 compared to R1 and R2 is shown.

Figure 7

Event free survival (EFS) and overall survival (OS) of patients with non-metastatic unilateral Wilms tumor and local stage III after preoperative chemotherapy treated according to the consecutive SIOP/GPOH trials and studies 9, 93-01 and 2001. Influence of lymph node involvement is shown.