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Are we making progress in curing advanced cervical cancer—again?
  1. Jacob Christian Lindegaard1,
  2. Primoz Petric2,
  3. Li-Tee Tan3,
  4. Peter Hoskin4,
  5. Maximilian P Schmid5,
  6. Ina Jürgenliemk-Schulz6,
  7. Umesh Mahantshetty7,
  8. Christian Kirisits5 and
  9. Richard Pötter5
    1. 1Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
    2. 2Department of Radiation Oncology, University Hospital Zürich, Zürich, Switzerland
    3. 3Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
    4. 4Mount Vernon Cancer Centre, Northwood, Middlesex, UK
    5. 5Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
    6. 6Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, Netherlands
    7. 7Radiation Oncology, Homi Bhabha Cancer Hospital and Research Center, Visakhapatnam, India
    1. Correspondence to Dr Jacob Christian Lindegaard, Department of Oncology, Aarhus University Hospital, 8200 Aarhus, Denmark; jacob.lindegaard{at}auh.rm.dk

    Abstract

    Major improvements in radiotherapy over the past two decades in the definitive treatment of locally advanced cervical cancer have significantly improved loco-regional control and survival, whereas little progress has been made with chemotherapy since the implementation of concomitant cisplatin 25 years ago. However, the randomized study INTERLACE (A phase III multicenter trial of weekly induction chemotherapy followed by standard chemoradiation versus standard chemoradiation alone in patients with locally advanced cervical cancer) of neoadjuvant chemotherapy presented recently, has shown significant improvement in survival with the use of six cycles of weekly carboplatin and paclitaxel. Although INTERLACE is yet to be published, neoadjuvant chemotherapy is already being advocated as the new standard, and studies are being designed with neoadjuvant chemotherapy followed by chemoradiation and brachytherapy as the standard arm. It is noteworthy that INTERLACE was initiated before the improvements in radiotherapy mentioned above were broadly implemented. The survival rate in the standard arm of INTERLACE was therefore inferior to the results obtained with the latest state-of-the-art external beam radiotherapy and image guided adaptive brachytherapy (EMBRACE, Magnetic Resonance Imaging (MRI)-Guided Brachytherapy in Locally Advanced Cervical Cancer). Moreover, patient selection impedes the comparison of INTERLACE with other studies as the patients included in INTERLACE were younger, had better performance status, and had less advanced disease than in other studies. Notably patients with involved para-aortic nodes were excluded. In this review, we discuss neoadjuvant chemotherapy in the frame of the EMBRACE studies and show how the impact of modern radiotherapy and patient selection affects the interpretation of the results of INTERLACE. This has led us to conclude that neoadjuvant chemotherapy is not needed for the majority of patients with cervical cancer treated with definitive modern radiotherapy, and may cause harm. However, it is possible that short course neoadjuvant chemotherapy may benefit a minor subgroup of patients who need to be identified. Comprehensive understanding, including cost utility analyses, are needed to draw conclusions regarding the potential benefit of neoadjuvant chemotherapy in low and middle income countries with limited access to modern radiotherapy.

    • Cervical Cancer
    • Brachytherapy
    • Radiotherapy, Image-Guided
    • Radiotherapy, Intensity-Modulated

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    Footnotes

    • Contributors Planning of the manuscript was done by JCL, PP, and RP. Figure 1 was drawn by PP and JCL. The tables were produced by JCL, RP, and CK. The manuscript was written by JCL with substantial contribution and support from all co-authors: PP, LTT, PH, MPS, IJ-S, UM, CK, and RP.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.