Factors Influencing Overall Survival in Patients with High Risk Renal Tumors
Majdee M. Islam, MD1, Amanda F. Saltzman, MD1, Arya Amini, MD2, Alonso Carrasco, Jr., MD1, Nicholas G. Cost, MD1.
1University of Colorado, Department of Surgery, Division of Urology, Aurora, CO, USA, 2University of Colorado, Department of Radiation Oncology, Aurora, CO, USA.
Background: Renal tumors are among the most common solid malignancies in the pediatric population. Of these pediatric tumors, those considered high risk include anaplastic Wilms tumor (AWT), clear cell sarcoma of the kidney (CCSK) and malignant rhabdoid tumor (RTK). The objective of our study was to identify factors impacting overall survival (OS) in children, adolescents and young adults with high risk pediatric renal tumors.
Methods: The National Cancer Database was queried for patients diagnosed with AWT, CCSK, or RTK between 2004–2013. Patients >30 years old were-excluded. Demographic, clinical and OS data were abstracted. OS between groups was compared graphically with a Kaplan-Meier curve. Univariate survival analysis (UVA) was performed with the log-rank test, with unadjusted Cox proportional hazards regression used to estimate hazard ratios (HR). Multivariate Cox regression analysis (MVA) was performed using OS as outcomes.
Results: A total of 349 patients were identified meeting study criteria; 133 (38.1%) with AWT, 120 (34.4%) with CCSK and 96 (27.5%) with RTK. Median age for AWT was 4yr, CCSK 2yr, RTK <1yr (p<0.001). Median time to last follow up was 43.3 months (range 1.3-126.2) for AWT, 49.3 months (range 0.4-125.4) for CCSK and 8.1 months (0.1-121.2) for RTK (p<0.001).
AWT and CCSK tumors were associated with larger diameter than RTK (10.5cm, 12cm, 8.3cm respectively; p=0.01). Patients with RTK were less likely to undergo surgery than those with AWT or CCSK (77.1% vs. 94% vs. 99%, p<0.001). Patients with RTK were less likely than patients with AWT or CCSK to receive chemotherapy (84.4% vs. 96.2% vs. 95%, p=0.013) and radiation therapy (52.1% vs. 81.2% vs. 86.7%, p<0.001). In addition, RTK was the most likely histology to be associated with lymph node (LN) involvement (23, 34%) compared to CCSK (32, 19.1%) and AWT (34, 25.8%), p=0.013. Estimated 5yr OS was 76.1% (95% CI 67.9-84.4) for AWT, 92.7% (95% CI 87.4-97.9) for CCSK and 33.5% (95% CI 23.1-43.9) for RTK (log-rank p<0.001, with all pairwise comparisons having p≤0.001), Figure 1.
UVA and MVA are shown in table 1. AWT (HR 3.372, p=0.032) and RTK histology (HR 12.595, p<0.001) were significantly associated with worse survival, while receipt of radiation therapy (HR 0.43, p=0.006) was associated with improved OS on multivariate analysis. LN positivity, LN density, margin status and undergoing surgical resection were not.
Conclusions: While high risk pediatric renal tumors are associated with poor outcomes, RTK is associated with worse outcomes than either AWT or CCSK. Receipt of radiation is significantly associated with improved outcomes.
Table 1: Cox regression analysis for OS
| Univariate | Multivariate | ||||||
| HR | 95% CI | p-value | HR | 95% CI | p-value | ||
| Histology CCSK AWT RTK | 1 3.685 17.441 | 1.605-8.463 7.933-38.345 | 0.002 <0.001 | 3.372 12.595 | 1.107-10.273 4.263-37.209 | 0.032 <0.001 | |
| Age (Categorical) 0 to 12yr 13 to 30yr | 1 0.979 | 0.397-2.413 | 0.979 | ||||
| Race White Black Other Unknown | 1 1.095 0.759 NA | 0.665-1.805 0.277-2.081 | 0.721 0.592 | ||||
| Gender Male Female | 1 1.232 | 0.815-1.865 | 0.323 | ||||
| Median Tumor Size (cm) | 0.994 | 0.989-0.998 | 0.01 | 0.999 | 0.992-1.006 | 0.84 | |
| LN Status Negative Positive Unknown | 1 2.944 3.007 | 1.709-5.073 7.786-5.061 | <0.001 <0.001 | 1 1.572 NA | 0.647-3.67 | 0.296 | |
| LNs examined | 0.983 | 0.948-1.019 | 0.353 | ||||
| LN Density, Median (Range) | 2.939 | 1.494-5.78 | 0.002 | 1.626 | 0.537-4.925 | 0.39 | |
| Surgery No Yes | 1 0.117 | 0.073-0.187 | <0.001 | 1 NA | |||
| Margin Status Negative Residual Tumor Unknown | 1 3.271 0.679 | 2.136-5.009 0.211-2.189 | <0.001 0.517 | 1 1.25 0.898 | 0.64-2.443 0.211-3.822 | 0.514 0.885 | |
| Radiation Therapy No Yes Unknown | 1 0.264 0.771 | 0.174-0.399 0.106-5.603 | <0.001 0.797 | 1 0.43 NA | 0.235-0.786 | 0.006 | |
| Chemotherapy No Yes Unknown | 1 0.551 0.451 | 0.266-1.138 0.056-3.609 | 0.107 0.453 | ||||
Figure 1: Kaplan Meier curve of OS by histology
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