Neoadjuvant chemotherapy followed by surgery in cervical cancer: past, present and future

Abstract

Background: Cisplatin-based concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. In view of the difficulties associated with implementation of standard radiation protocols in low- and middle-income countries and the associated toxicities of chemoradiation, neoadjuvant chemotherapy followed by surgery has been tried as an alternative treatment for locally advanced cervical cancer.

Methods: A comprehensive review was undertaken of the existing literature, caveats and potential avenues of neoadjuvant chemotherapy followed by surgery compared with chemoradiation in locally advanced cervical cancer.

Results: Randomized studies conducted in the pre-chemoradiation era comparing neoadjuvant chemotherapy followed by surgery with definitive radiotherapy alone showed favorable outcomes with the chemo-surgical approach. However, contemporary studies evaluating the role of neoadjuvant chemotherapy followed by surgery have failed to establish this approach as the standard. About 25-30% of patients who undergo neoadjuvant chemotherapy remain inoperable and require definitive chemoradiation. A similar proportion of patients would require adjuvant (chemo)radiation after neoadjuvant chemotherapy followed by surgery, resulting in excessive morbidity. Evaluation of time trends across the past few decades reveals that the advancements in delivery of radiation (external beam and brachytherapy) have translated into improvement in outcomes for locally advanced cervical cancer, while a similar trend was not observed for surgery or chemotherapy.

Conclusion: Neoadjuvant chemotherapy followed by surgery cannot be considered a standard of care in patients with locally advanced cervical cancer. This approach needs further clinical research to generate robust high-quality evidence especially for the sub-sets that might potentially benefit in terms of survival, toxicity and quality of life, against the gold standard treatment of concomitant chemoradiation.

Keywords: cervical cancer; radiotherapy; surgery.