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Pretreatment Proliferation Parameters Do Not Add Predictive Power to Clinical Factors in Cervical Cancer Treated with Definitive Radiation Therapy

Departments of Radiation Oncology [R. W. T., S. J., M. M., A. W. F.], Pathology [W. C.], Biostatistics [M. P.], and Division of Experimental Therapeutics [R. P. H.], Princess Margaret Hospital/Ontario Cancer Institute, University Health Network, and Toronto-Sunnybrook Regional Cancer Centre [S. W.], University of Toronto, Toronto, Ontario, M5G 2M9 Canada

Purpose: To examine the prognostic value of tumor proliferation measurements in women with carcinoma of the uterine cervix. We report an update of a prospective study focusing on whether pretreatment proliferation parameters are associated with clinical outcome, relative to other established clinical factors.

Materials and Method: One hundred and one patients were recruited into the study from years 1991 to 1999. The LI for in vivo bromodeoxyuridine incorporation by the tumor and the potential doubling time (T_pot) were determined by flow cytometry (fc). LI and its staining pattern were also assessed by immunohistochemistry (ih) using tissue sections. Apoptosis was assessed histologically using morphological criteria. Patients were treated with definitive radiation therapy.

Results: A successful fc measurement for LI-fc and T_pot was possible in 95 patients (94%). The median/mean LI-fc was 6.6/7.6% (range 1.4–36.1%), and for LI-ih, 10.8/11.5%. To date, 43 patients have died of disease, and the median follow-up for alive patients is 6.2 years (range 1.3–9.3 years). Among 88 patients who completely responded to treatment, 40 patients have relapsed (14 pelvic, 23 distant, and 3 pelvic and distant). In univariate analysis, the significant factors for adverse disease-free survival were large tumor size (P = 0.0001), low hemoglobin (P = 0.001), pelvic lymph node status (P = 0.004), stage (P = 0.013), and overall treatment time (P = 0.0008). In multivariate analysis, only tumor size, pelvic lymph node status, and overall treatment time remained significant for disease-free survival. LI-fc, LI-ih, T_pot, ploidy, pattern of bromodeoxyuridine staining, and apoptosis were not significantly associated with clinical outcome in univariate or multivariate analyses.

Conclusions: These mature data indicate that none of the pretreatment proliferation parameters have prognostic significance in the radical radiotherapy of carcinoma of the uterine cervix, despite the significance of overall treatment time for treatment outcome.

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