Clinical Outcome and Biological Predictors of Relapse After Nephrectomy Only for Very Low-risk Wilms Tumor: A Report From Children's Oncology Group AREN0532.
To determine if observation alone after nephrectomy in very low-risk Wilms tumor (defined as stage I favorable histology Wilms tumors with nephrectomy weight <550g and age at diagnosis <2 years) results in satisfactory event-free survival and overall survival, and to correlate relapse with biomarkers.



The AREN0532 study enrolled patients with very low-risk Wilms tumor confirmed by central review of pathology, diagnostic imaging, and surgical reports. After nephrectomy, patients were followed without adjuvant chemotherapy. Evaluable tumors were analyzed for WT1mutation, 1p and 16q copy loss, 1q copy gain, and 11p15 imprinting. The study was powered to detect a reduction in 4-year EFS from 87% to 75% and overall survival from 95% to 88%.



A total of 116 eligible patients enrolled with a median follow up of 80 months (range: 5-97 months). Twelve patients relapsed. Estimated 4-year event-free survival was 89.7% (95% confidence interval 84.1-95.2%) and overall survival was 100%. First sites of relapse were lung (n = 5), tumor bed (n = 4), and abdomen (n = 2), with one metachronous tumor in the contralateral kidney (n = 1) at a median time of 4.3 months for those who relapsed (range 2.3-44 months). The presence of intralobar (P = 0.46) or perilobar rests (P = 1.0) were not associated with relapse (P = 0.16). 1q gain, 1p and 16q loss, and WT1 mutation status were not associated with relapse. 11p15 methylation status was associated relapse (20% relapse with loss of heterozygosity, 25% with loss of imprinting, and 3.3% relapse with retention of the normal imprinting (P = 0.011)).



Most patients meeting very low-risk criteria can be safely managed by nephrectomy alone with resultant reduced exposure to chemotherapy. Expansion of an observation alone strategy for low-risk Wilms tumor incorporating both clinical features and biomarkers should be considered.
*IWK Health Center, Dalhousie University, Halifax, Nova Scotia, Canada †Ann and Robert H. Lurie Children's Hospital, Chicago, IL ‡Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA §Department of Biostatistics, University of Florida, Gainesville, FL ¶Boston Children's Hospital, Boston, MA ||Division of General and Thoracic Surgery, Seattle Children's Hospital, Seattle, WA **Connecticut Children's Medical Center, Hartford, CT ††Primary Children's Hospital, Salt Lake City, UT ‡‡University of Michigan, Ann Arbor, MI §§Washington University School of Medicine in St. Louis, St. Louis, MO ¶¶Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL ||||Anderson Cancer Center, Houston, TX ***Children's Oncology Group Data Center, University of Florida, Gainesville, FL †††Cincinnati Children's Hospital Medical Center, Cincinnati, OH ‡‡‡Alberta Health Services, Edmonton, Alberta, Canada §§§Merck Research Laboratories - Oncology, North Wales, PA ¶¶¶Children's National Medical Center, District of Columbia, WA.
Conrad V
CV
Fernandez
Elizabeth J
EJ
Perlman
Elizabeth A
EA
Mullen
Yueh-Yun
YY
Chi
Thomas E
TE
Hamilton
Kenneth W
KW
Gow
Fernando A
FA
Ferrer
Douglas C
DC
Barnhart
Peter F
PF
Ehrlich
Geetika
G
Khanna
John A
JA
Kalapurakal
Tina
T
Bocking
Vicky
V
Huff
Jing
J
Tian
James I
JI
Geller
Paul E
PE
Grundy
James R
JR
Anderson
Jeffrey S
JS
Dome
Robert C
RC
Shamberger
D017677:Age Distribution; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000473:pathology; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000379:methods* / Q000401:mortality; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D016019:Survival Analysis; D057832:Watchful Waiting / Q000379:methods*; D009396:Wilms Tumor / Q000401:mortality / Q000473:pathology / Q000601:surgery*
D014408:Biomarkers, Tumor