title: Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ib squamous carcinoma of the cervix: the final results.
abstract: OBJECTIVE
  To determine if three courses consisting of 50 mg/m2 cis-platinum, 1 mg/m2 vincristine, and 25 mg/m2 bleomycin (day 1-3) at 10-day intervals can improve survival before Wertheim-Meigs + radiotherapy.
  
  
  METHODS
  Two hundred five unselected stage Ib patients (having tumors > 2 cm in diameter) were divided into two groups at random: (1) The group control consisted of 103 patients (56 bulky, > 4 cm diameter) treated with Wertheim-Meigs (if the tumor was resectable with free surgical margins) + adjuvant radiotherapy to whole pelvis (extended field radiation was used only in patients with paraaortic lymph node metastases). When the tumor was unresectable, a surgical staging was performed and radiotherapy was the chosen treatment. (2) Neoadjuvant (102 patients, 61 bulky) had neoadjuvant chemotherapy and then the same treatment as the control patients.
  
  
  RESULTS
  After 67 (31-102) months of follow-up, no difference was seen in tumors > 2 and < 4 cm in both groups (C = 77% vs N = 82%), but statistically significant differences were seen in survival and disease-free survival, in bulky tumors, and between patients with neoadjuvant chemotherapy + Wertheim-Meigs + radiotherapy (80%) and the control (61%). This was due to an increased operability that was substantially improved in bulky tumors in the neoadjuvant chemotherapy group (61/61, 100%) vs control (48/56, 85%; P < 0.01). After 7 years of follow-up, the outcome of the unresectable bulky control group of patients is significantly worse (14%) than that of the resectable group (69%; P < 0.001). With regard to recurrences, a significant decrease in pelvic failures in the neoadjuvant chemotherapy group was observed (P < 0.001). Survival was improved in bulky resectable cases (N = 81% vs C = 69%, P < 0.05). Pathological findings for the surgical specimens revealed differences between both groups because all the risk factors such as parametrial and lymph node metastases, tumor bulk, and vascular embolism had been decreased (P < 0.001).
  
  
  CONCLUSIONS
  Neoadjuvant chemotherapy can improve survival because of increased operability with free survival margins and a decrease in pathologic risk factors in unselected, bulky (> 4 cm diameter) stage Ib patients.
authors.affiliation: Gynecologic Oncology Unit, First Chair of Gynecology, Buenos Aires University, Argentina.
authors.forename: J E
authors.initials: JE
authors.lastname: Sardi
authors.forename: A
authors.initials: A
authors.lastname: Giaroli
authors.forename: C
authors.initials: C
authors.lastname: Sananes
authors.forename: M
authors.initials: M
authors.lastname: Ferreira
authors.forename: A
authors.initials: A
authors.lastname: Soderini
authors.forename: A
authors.initials: A
authors.lastname: Bermudez
authors.forename: L
authors.initials: L
authors.lastname: Snaidas
authors.forename: S
authors.initials: S
authors.lastname: Vighi
authors.forename: N
authors.initials: N
authors.lastname: Gomez Rueda
authors.forename: G
authors.initials: G
authors.lastname: di Paola
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D001761:Bleomycin; D014750:Vincristine; D002945:Cisplatin