Pelvic Radiation With Concurrent Chemotherapy versus Pelvic and Para-Aortic Radiation for High-Risk Cervical Cancer: An Update of RTOG 90-01

Reviewer: Ryan Smith, MD
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Last Modified: October 7, 2002

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Presenter: Patricia Eifel
Presenter's Affiliation: RTOG
Type of Session: Plenary

Background

    There have been several studies documenting the efficacy of chemoradiation over radiation alone in the treatment of locally advanced cervical cancer. One of these studies, published in the NEJM in 1999, was RTOG 90-01, which randomized patients between para-aortic (PA) node + pelvic radiation vs. chemotherapy + pelvic radiation. This initially showed an increase in local control (LC), disease specific survival (DSS), and overall survival (OS) for the chemoradiation arm. This presentation reports an update of RTOG 90-01 and denotes the toxicity data not evaluable at the first publication.

Materials and Methods

  • 403 patients were entered into this prospective, randomized study.
  • Patients in the RT alone group (RT) were treated with whole pelvis radiation with extension of a "chimney" field to the bottom of L1 to treat the PA nodes. This was taken to a dose of 45 Gy, with LDR brachytherapy boost to a dose of 86-87 Gy to point A.
  • Patients in the chemoradiation group (CRT) received 45 Gy via external beam radiation therapy to a whole pelvis field (without extension to include the PA nodes). Concurrent chemotherapy was given consisting of: Cisplatin 75 mg/m2 + 5-FU 4g/m2 over 96 hour infusion. This chemotherapy was repeated q 3 weeks x 3.
  • >80% of patients had KPS gretaer than or equal to 90.
  • 90% had squamous cell cancer
  • Patients were stratified by FIGO stage (IB-IIB vs. III-IVa)
  • All patients had PA node investigation via lymphangiogram or surgical exploration (25%)
  • Median follow up is now 4.6 years, and 6.6 years in the survivors

Results

  • Outcomes were better for patients treated with chemoradiation
  • OS was 73% vs. 52%
  • OS in patients with Stage I-II disease was 79% vs. 55%
  • OS in patients with Stage III-IVa disease (118 patients) was 59% vs. 45% (p=.07),
  • Local failure was 18% vs. 34%
  • Development of DM was 18% vs. 31%
  • PA node failure was 7% (CRT) vs. 4% (RT)
  • Major late complications were 14% (RT) vs. 12% (CRT). They were mostly rectal or large bowel complications.

Author's Conclusions

  • Cisplatin + 5-FU concurrent with radiation therapy reduces the risk of recurrence by 50%
  • This translated into a significant survival gain for the CRT group
  • There were gains in Stage III-IVa disease, though the greatest advantage was seen in patients with Stage I-II disease
  • This outcome advantage was gained without increase in toxicity.

Clinical/Scientific Implications

    With several studies documenting increased efficacy of chemoradiation over radiation alone in the treatment of locally advanced cervical cancer, this has become the indisputable standard of care for these patients. The only possible weakness in this study, now that it has longer follow up, is that only 25% had PA nodes that were surgically investigated. However, lymphangiogram has documented high sensitivity in predicting PA nodal metastases. The question remains of what is the best chemotherapy regimen to use in this situation? This study is the only one of the 5 published in this area that show a decrease in local failure as well as distant failure. Therefore, perhaps cisplatin + 5-FU is better than cisplatin alone. However, weekly cisplatin has advantages as well, mainly in the ability to dose adjust more quickly if toxicity arises. There are additional questions including the role of hemoglobin, the appropriate imaging required, and the question of HDR as a substitute for tradiational LDR brachytherapy boost. However, the longer follow up of this study lends more proof that chemoradiation should be the standard of care in locally advanced cervical cancer, with the possibility of 5-FU and cisplatin being the optimal regimen.

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