When do you consider neoadjuvant chemotherapy prior to definitive chemoradiation for cervical cancer?
Although we are occassionally referred patients for "consolidation" of loco-regional disease after favorable responses to chemotherapy for stage IVB disease, we very rarely give neoadjuvant chemotherapy for patients with stage I-IVA cancers with nodal disease confined to the pelvis and PA regions. Even SCV+ IVB cancers are usually treated with initial chemo-RT.
Although there are still some advocates for neoadjuvant chemotherapy, after detailed review of the literature I have found little actual evidence that neoadjuvant chemotherapy before RT helps to achieve the ultimate goal of curative eradication of tumor, particularly when compared with up-front chemoRT. Although initial responses to chemotherapy can be impressive, meta-analyses have, overall, shown no benefit from neoadjuvant chemotherapy in patients with cervical cancer. A 2004 COCHRAN meta-analysis suggested that a subset of patients who had a very short intensive course of neoadjuvant seemed to have a better outcome than patients treated with RT alone; but only 3 trials had an OR<1—all reported from the same group (Sardi et al.) Notably, Meta analysis of the 11 trials that used more prolonged neoadjuvant CT actually revealed a significantly worse outcome for patients who received neoadjuvant CT (vs RT alone) with an OR = 1.3. This raises the question whether the improvement suggested from the shorter neoadjuvant course reflected a residual sensitizing effect from chemo given within days of the start of RT. And, of course, none of these trials were compared with chemoRT, which has consistently be demonstrated to be far superior to RT alone. One problem with the use of neoadjuvant chemotherapy it is inevitably more difficult to deliver subsequent concurrent Chemo-RT.
Evidence from other disease sites are consistent with these findings. In particular, large meta-analyses in patients treated for head and neck cancers (many of which are also HPV-related) have yielded strong evidence for the superiority of concurrent chemotherapy over neoadjuvant. A recent meta-analysis also specifically demonstrated greater toxicity but no improvement in outcome when neoadjuvant was added to concurrent chemo-RT. Meta analyses of treatment for lung cancer and anal cancer have yielded similar conclusions.
All of the specific situations listed above (organ invasion, geometry, nodal size) are generally as easily addressed with chemoRT and adaptive planning. Except for patients who have a large fistula, we find that brachytherapy is virtually always feasible. There may be very extreme cases where nodal disease is truly massive (e.g., extensive confluent masses with axial diameters > 4-5 cm extending to the high PANs or SCV) where we might consider a short course of neoadjuvant chemotherapy. However, we would do this more as a method of triage. The evidence (particularly from head and neck data) does suggest that, although neoadjuvant chemotherapy does not appear to greatly influence the chance of cure, a good response to chemotherapy does tend to predict a better outcome with RT.
There is some early evidence that neoadjuvant chemotherapy may allow somewhat expanded indications for fertility-sparing surgery in patients with IB cervical cancers who would otherwise be marginal candidates. Again, this is consistent with findings in other disease sites where neoajuvant chemotherapy can be used to triage and expand indications for organ preservation.
Eifel, P. J. and A. H. Klopp (2017). Gynecologic radiation oncology. A practical guide. Philadelphia, Wolters Kluwer.
Eifel PJ. Chemoradiotherapy: Neoadjuvant, Concomitant, Sequential, or Monomodality Treatment? In: Textbook of Gynaecological Oncology. Gunes Publishing: Ankara, Turkey, 1405-1412, 2016.
Tumor size or local extensions to bladder or rectum are not indication for NACT as it would delay local treatment with no improvement in outcome