Pattern of Failures and Clinical Outcome of Patients with Locally Advanced Cervical Cancer Treated with a Tailored Integrated Therapeutic Approach

Aim: To review a tailored treatment with concurrent chemoradiotherapy (CT/RT) or neoadjuvant chemotherapy (NACT) followed by radical hysterectomy in locally advanced cervical cancer. Patients and Methods: One hundred and four patients were treated with a tailored therapeutic approach. CT/RT was the standard treatment for patients with stage Ib2- IIb disease aged more than 70 years, or with high surgical risk, as well as for those with stage III-IV disease. NACT followed by radical hysterectomy was the treatment of choice for patients with stage Ib 2 -IIb disease, maximum age of 70 years and good performance status. Results: For the 61 women who underwent CT/RT, 5-year disease-free (DFS) survival and 5-year overall survival (OS) were 62% and 71%, respectively. Patient outcome was associated with the clinical response to CT/RT (complete responders versus others: 5-year DFS, 81% versus 19%, p<0.001; 5-year OS, 84% versus 37%, p=0.001). For the 43 women who underwent NACT, 5-year DFS and 5-year OS were 66% and 75%, respectively. Patient outcome was associated with the pathological response to chemotherapy (optimal responders versus others: 5-year DFS, 89% versus 62%, p=0.03; 5-year OS, 90% versus 72%, p=0.05). Conclusion: Tailored treatments obtained satisfactory clinical outcomes in locally advanced cervical cancer. Optimal pathological response to NACT has been found to be a surrogate endpoint of OS. The identification of biological variables able to predict response to NACT is strongly warranted for an accurate selection of patients who may really benefit from chemosurgical treatment. Radical radiotherapy, consisting of external pelvic beam irradiation and brachytherapy, has long been the treatment of choice for locally advanced cervical cancer. Concurrent cisplatin-based chemoradiotherapy is currently accepted as the new standard of care. Five prospective randomised trials showed a significant improvement of the clinical outcome for patients who received this combined treatment compared with those who received radiotherapy alone (1-7). A meta-analysis of 13 randomised clinical trials revealed that concurrent chemoradiotherapy obtained a 6% improvement in 5-year survival (hazard ratio (HR)=0.81, 95% confidence interval (CI)=0.71-0.91, p=0.0006) with respect to radiotherapy alone (8). Neoadjuvant chemotherapy followed by radical surgery appears to be an interesting alternative therapeutic option, at least for patients with stage Ib2-IIb disease (9-14). A meta- analysis assessed six randomised trials comparing neoadjuvant chemotherapy and surgery versus surgery in women with early or locally advanced cervical cancer (11). Exploratory analyses of pathological responses showed a significant decrease in adverse pathological findings with neoadjuvant chemotherapy (odds ratio (OR)=0.54, 95% CI=0.39-0.73, p<0.0001 for lymph node status and OR=0.58, 95% CI=0.41-0.82, p=0.002 for parametrial infiltration). The aim of the present retrospective investigation was to assess the pattern of failures and the clinical outcome of patients with locally advanced cervical cancer treated with a tailored integrated therapy. Patients and Methods The present study retrospectively assessed 104 patients with locally advanced cervical cancer referred to the multidisciplinary Committee of Gynaecologic Oncology of the Pisa University Hospital between 1999 and 2009, and treated with either exclusive concurrent chemoradiotherapy or neoadjuvant chemotherapy followed by radical hysterectomy. Patients with poor performance status treated with radiotherapy alone were not included in this analysis.