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Dose-dense neoadjuvant chemotherapy before radical surgery in cervical cancer: a retrospective cohort study and systematic literature review
  1. Giuseppe Caruso1,2,
  2. Simone Bruni3,
  3. Mariateresa Lapresa3,
  4. Luigi A De Vitis1,3,
  5. Gabriella Parma3,
  6. Valentina Minicucci3,
  7. Ilaria Betella3,
  8. Gabriella Schivardi3,
  9. Fedro Peccatori3,
  10. Roberta Lazzari4,
  11. William Cliby1,
  12. Giovanni Damiano Aletti3,5,
  13. Vanna Zanagnolo3,
  14. Angelo Maggioni3,
  15. Nicoletta Colombo3,6 and
  16. Francesco Multinu3
  1. 1 Department of Obstetrics and Gynecology, Division of Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota, USA
  2. 2 Department of Maternal and Child Health and Urological Sciences; Department of Experimental Medicine, University of Rome La Sapienza, Rome, Italy
  3. 3 Department of Gynecology, European Institute of Oncology (IEO) IRCCS, Milan, Italy
  4. 4 Department of Radiotherapy, European Institute of Oncology (IEO) IRCCS, Milan, Italy
  5. 5 Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
  6. 6 Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
  1. Correspondence to Dr Francesco Multinu, Department of Gynecology, European Institute of Oncology, Milan 20141, Italy; Francesco.Multinu{at}


Objective To evaluate the role of dose-dense neoadjuvant chemotherapy followed by radical hysterectomy in reducing adjuvant radiotherapy in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB1-IB2/IIA1 cervical cancer with disrupted stromal ring and as an alternative to concurrent chemoradiotherapy in FIGO 2018 stages IB3/IIA2.

Methods This was a retrospective cohort study including patients with FIGO 2018 stage IB1-IIA2 cervical cancer undergoing dose-dense neoadjuvant chemotherapy at the European Institute of Oncology in Milan, Italy between July 2014 and December 2022. Weekly carboplatin (AUC2 or AUC2.7) plus paclitaxel (80 or 60 mg/m2, respectively) was administered for six to nine cycles. Radiological response was assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria. The optimal pathological response was defined as residual tumor ≤3 mm. Kaplan–Meier curves were used to estimate survival rates. A systematic literature review on dose-dense neoadjuvant chemotherapy before surgery for cervical cancer was also performed.

Results A total of 63 patients with a median age of 42.8 years (IQR 35.3–47.9) were included: 39.7% stage IB-IB2/IIA1 and 60.3% stage IB3/IIA2. The radiological response was as follows: 81% objective response rate (17.5% complete and 63.5% partial), 17.5% stable disease, and 1.6% progressive disease. The operability rate was 92.1%. The optimal pathological response rate was 27.6%. Adjuvant radiotherapy was administered in 25.8% of cases. The median follow-up for patients who underwent radical hysterectomy was 49.7 months (IQR 16.8–67.7). The 5-year progression-free survival and overall survival were 79% (95% CI 0.63 to 0.88) and 92% (95% CI 0.80 to 0.97), respectively. Fifteen studies including 697 patients met the eligibility criteria for the systematic review. The objective response rate, operability rate, and adjuvant radiotherapy rate across studies ranged between 52.6% and 100%, 64% and 100%, and 4% and 70.6%, respectively.

Conclusions Dose-dense neoadjuvant chemotherapy before radical surgery could be a valid strategy to avoid radiotherapy in stage IB1-IIA2 cervical cancer, especially in young patients desiring to preserve overall quality of life. Prospective research is warranted to provide robust, high-quality evidence.

  • Cervical Cancer
  • Hysterectomy
  • Radiotherapy
  • Quality of Life (PRO)/Palliative Care

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • NC and FM contributed equally.

  • Contributors GC, SB, ML: conceptualization, data curation, investigation, methodology, resources, software, validation, visualization, writing - original draft, writing - review and editing. LADV, GP, VM, IB, GS, FP, RL, WC, GDA, VZ, AM: validation, writing - review and editing. NC, FM: conceptualization, project administration, validation, supervision, writing - review and editing. All authors read and approved the final manuscript for publication. GC accepts full responsibility for the finished work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

  • 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.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.