Outcome of clear cell sarcoma of the kidney (CCSK) treated on the National Wilms Tumor Study-5 (NWTS)

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 4, 2006

Presenter: Breslow EJ et al.
Presenter's Affiliation: Children's National Medical Center, Washington D.C.
Type of Session: Scientific


  • CCSK originally described in early 1970s and characterized by tendency to metastasize to bone as well as propensity for late relapses
  • Improvements in overall survival (OS) have been demonstrated from NWTS 1-4 (increase of 33% to 83%)
    • NTWS 1-3 showed benefit to addition of doxorubicin to chemotherapy regimen
    • NTWS-3 showed no benefit to addition of cyclophosphamide to chemotherapy regimen
    • NWTS-4 showed relapse-free survival (RFS) benefit to increased length of treatment with 3 chemotherapy drugs (15 versus 6 months) with no effect on OS
  • Objective of NWTS-5 to improve outcome with addition of cyclophosphamide and etoposide

Materials and Methods

  • Prospective single-arm study ongoing between August 1995 and June 2002
  • Eligibility requirements included age < 16; centrally-confirmed pathologic diagnosis; and staging evaluation including CT imaging of primary site and lungs, CT/MR imaging of brain, bone survey, bone scan, bone marrow aspiration
  • Treatment consisted of a 24 week regimen of vincristine/doxorubicin/cyclophosphamide alternating with cyclophosphamide/etoposide as well as 10.8 Gy external beam irradiation to the resected tumor site as well as to metastatic sites of tumor


  • Out of 123 enrolled patients, 110 were eligible for assessment, with a median age of 22 years, and a majority of which were males (69%), Caucasian (63%), and presented with either Stage II or III disease
  • Median follow-up for all patients was 4.6 years
  • 5-year event-free survival (EFS) was 78.9%
  • 5-year OS was 88.7%
  • A total 22 events were noted (21 relapses and 1 bowel obstruction), 20/21 relapses occurred within 3 years of initial treatment, and most relapses were in the brain (11/21)
  • Increased metastases to the brain and decreased metastases to the lungs were found as compared to NTWS-4 and earlier SIOP and UKCCSG trials
  • In Stage II and III patients, only spread of disease to lymph nodes significantly impacted OS (p=0.057)

Author's Conclusions

  • Outcome for patients treated on NWTS-5 is similar versus NWTS-4 and earlier SIOP and UKCCSG trials
  • Stage is highly predictive of outcome
    • Stage I patients have a very good prognosis
    • Stage IV patients still have a very bad prognosis
    • Stage III patients with nodal spread of disease have a bad prognosis
  • Future Children’s Oncology Group (COG) protocols will use the same treatment (as per NWTS-5) for Stage I-III patients, and add carboplatin in patients with Stage IV disease
Clinical/Scientific Implications
  • It is unclear that the addition of cyclophosphamide and etoposide in rotation with vincristine/doxorubicin/cyclophosphamide is warranted in further trials, as etoposide is known to increase the risk of second malignancy, and no significant gains were made in either EFS or OS versus the NWTS-4 which did not employ etoposide
  • Future protocol amendments include the addition of carboplatin to the chemotherapy regimen (based on preliminary results of data from the relapse protocols of NWTS 4-5 that employ carboplatin) for patients with Stage IV disease, and the examination of the necessity of radiation in patients with Stage I disease