Concurrent chemoradiotherapy for cervical cancer: background including evidence-based data, pitfalls of the data, limitation of treatment in certain groups

Yukiharu Todo, Hidemichi Watari, Yukiharu Todo, Hidemichi Watari

Abstract

Concurrent chemoradiotherapy (CCRT) is regarded as the standard treatment for locally advanced uterine cervical cancer (LACC), including stage Ib2-IVa disease [International Federation of Gynecology and Obstetrics (FIGO) staging]. However, approximately a third of eligible patients in previous studies died of LACC despite receiving CCRT. The therapeutic significance of CCRT alone in stage III-IVa disease has not yet been confirmed. Effective treatment of some LACC is beyond the scope of CCRT. The objective of the present review is to highlight some challenging work aimed at overcoming this seemingly intractable disease. CCRT with increased peak concentrations of cisplatin (CDDP), surgery following CCRT, adjuvant chemotherapy (CT) following CCRT, and neoadjuvant CT followed by CCRT are strategies expected to enhance the therapeutic efficacy of CCRT. If patients with LACC were divided into those with low-risk or high-risk systemic disease or prognoses, novel strategies should be assessed in the group with high-risk disease.

Keywords: Concurrent chemoradiotherapy (CCRT); adjuvant chemotherapy (CT); locally advanced cervical cancer (LACC).

Figures

Figure 1
Figure 1
Protocol designs of two randomized controlled studies that CCRT alone with CCRT followed by adjuvant CT. (A) Multinational B9E-MC-JHQS, (B) OUTBACK trial. CCRT, compare concurrent chemoradiotherapy; CT, chemotherapy; XRT, external-beam radiation; BRT, brachytherapy; CDDP, cisplatin; GEM, gemcitabine; PTX, paclitaxel; CBDCA, carboplatin.
Figure 2
Figure 2
Protocol designs of INTERLACE trial studies, which compared CCRT alone with neoadjuvant CT followed by CCRT. #, Exclusion criteria includes FIGO IIIA disease and positive lymph nodes (imaging or histological) above the aortic bifurcation. CCRT, compare concurrent chemoradiotherapy; XRT, external-beam radiation; BRT, brachytherapy; CT, chemotherapy; CDDP, cisplatin; PTX, paclitaxel; CBDCA, carboplatin.
Figure 3
Figure 3
Neoadjuvant CT was remarkably efficacious in a patient who had a large-sized cervical tumor (A), para-aortic lymph node enlargement (B: arrow) and multiple pelvic lymph node enlargement (C: arrow). After one course of combined CT (PTX 180 mg/m2 and cisplatin 60 mg/m2), the size of local disease was extremely reduced (D) and multiple lymph node enlargement disappeared (E). The patient received CCRT after two cycles of neoadjuvant CT and achieved a long-term disease-free survival period of 72 months. CT, chemotherapy; PTX, paclitaxel; CCRT, compare concurrent chemoradiotherapy.

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