Locally advanced cervical adenocarcinoma: is there a place for chemo-surgical treatment?

The increased frequency and poor prognosis of cervical adenocarcinoma call for new therapeutic strategies, especially in locally advanced disease. Combined neoadjuvant chemotherapy (NACT)-radical surgery (RS) has been investigated to assess its feasibility and the possible impact on disease outcome. Data were pooled from three consecutive trials on a total of 42 patients with FIGO Stage IB-IIA >4 cm (9), IIB (19), and IIIB (14) cervical adenocarcinomas. NACT regimens consisted of cisplatin (P), bleomycin (B) and methotrexate, high-dose PB, and P and doxorubicin combinations for one to three cycles. Responding patients underwent RS while those still ineligible for RS underwent radiotherapy. Fisher and chi squared tests were used to detect significant factors affecting response to NACT. Cox multivariate regression analysis was used to evaluate parameters affecting response and survival. Medians and life tables were computed by the method of Kaplan and Meier. Median follow-up times were 56 (17-95) and 54 months (15-92) from enrollment and RS, respectively. NACT-induced toxicity was generally mild and did not compromise RS when indicated. The 33 (79%) responders underwent laparotomy, while the 9 nonresponders received radiotherapy. RS was feasible in 29 (69%) patients. Macroscopic intraperitoneal tumor (IPT) excluded abandoning RS in 4 cases. Mild to moderate RS-related complications were seen in 41% of cases with the same pattern as in the absence of any prior treatment. In patients undergoing RS, node metastasis and microscopic IPT were detected in 2 (7%) and 3 (10%) patients, respectively. The 5-year overall and disease-free survivals were 71% (100% IB-IIA and 84% IIB vs 36% IIIB; P = 0.001) and 88%, respectively. None of the nonresponders survived (median 10 months, 6-25), compared with an 84% 5-year survival of responders (P < 0.001). FIGO stage and parametrial involvement significantly predicted response to NACT which was the only independent variable affecting survival (P = 0.006). This retrospective study provided evidence of the chemosensitivity of locally advanced cervical adenocarcinoma and that chemoresponsiveness is the most potent predictor of cure, as demonstrated in squamous cell cervical cancer. Combined NACT and RS is a feasible treatment which seems to be able to improve the outcome of Stage IB-IIB cervical adenocarcinoma. Randomized trials comparing this new strategy with conventional treatments seem to be warranted.