Concomitant radiochemotherapy plus surgery in locally advanced cervical cancer: update of clinical outcome and cyclooxygenase-2 as predictor of treatment susceptibility

Oncology. 2004;67(2):103-11. doi: 10.1159/000080995.

Abstract

Objective: We have updated our findings on the efficacy of concomitant radiochemotherapy plus radical surgery in a larger series of patients (n = 54) with locally advanced cervical cancer (LACC). We also investigated the role of cyclooxygenase-2 (COX-2) in this clinical setting.

Methods: Radiotherapy was administered to the whole pelvic region (1.8 Gy/day, totaling 39.6 Gy) in combination with cisplatin (20 mg/m2) and 5-fluorouracil (1,000 mg/m2) (both on days 1-4 and 27-30). Radical surgery was performed 5-6 weeks after the end of treatment.

Results: A clinical complete or partial response was observed in all 53 evaluable patients (75.5 and 24.5%, respectively). At pathological examination, 23 of 51 patients (45.1%) undergoing radical surgery showed complete response to treatment, 18 patients (35.3%) only had microscopic residual disease, 6 patients (11.7%) had a partial response and 4 (7.8%) had no change in their disease. When logistic regression was applied, the FIGO stage (chi2 = 5.28, p = 0.021) and tumor to stroma COX-2 ratio (chi2 = 4.72, p = 0.029) retained an independent role in the prediction of the pathologic response to treatment. The 3-year disease-free survival (DFS) was 75.2%, with local relapse-free survival of 86.2% and metastasis-free interval of 89.9% at 3 years. Cases with a high COX-2 ratio showed a shorter DFS than cases with a low COX-2 ratio (p = 0.016). A direct association was shown between COX-2 ratio values and risk of recurrence, as assessed by Cox analysis using COX-2 ratio values as a continuous covariate (chi2 = 3.94, p = 0.047).

Conclusion: This study confirms the possibility of achieving a very high rate of pathological responses in LACC patients administered chemoradiation plus surgery (3-year DFS 75.2%). Moreover, COX-2 status may play a role in the prognostic characterization and prediction of tumor response.

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Cyclooxygenase 2
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Hysterectomy* / methods
  • Immunohistochemistry
  • Isoenzymes / analysis*
  • Logistic Models
  • Lymph Node Excision
  • Membrane Proteins
  • Middle Aged
  • Neoadjuvant Therapy* / methods
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prostaglandin-Endoperoxide Synthases / analysis*
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant
  • Risk Assessment
  • Treatment Outcome
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / enzymology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy*
  • Uterine Cervical Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Cisplatin
  • Fluorouracil