Urinary cyclic GMP after treatment of gynecological cancer.: A prognostic marker of clinical outcome

Background: The search for biological markers to predict malignant disease and its recurrence, or to monitor the effectiveness of treatment is a continuous process in medicine. Several years ago, urinary excretion of cGMP in urine was found to be a sensitive predictor in the follow-up of ovarian cancer and of monitoring treatment of cancer of the uterine cervix. Patients and Methods: In the present study, 2 7 patients with gynecological cancer, including cancer of the uterine cervix (n = 13), cancer of the uterine corpus (n = 8) and cancer of the ovaries (n = 6), were monitored for 10 years. Blood and urinary samples were taken before primary treatment (baseline sample) and three months thereafter (three-month sample). The serum levels of CEA, CA-125 and PIIINP and urine excretion of cGMP and cAMP were determined. Creatinine levels in serum and urine were employed to determine renal clearance. Results: After 10 years' observation of women with cancer of the uterine cervix, seven patients showed no relapse and cGMP levels in baseline samples and three-month samples were 36.8 +/- 4.1 and 24.9 +/- 4.4 nmol cGMP/mu mol creatinine (mean +/- SEM, p < 0.01), respectively. The levels in patients (n = 6) with relapse after 10 years' observation were 32.8 +/- 4.0 (baseline sample) and 43.5 +/- 4.2 (three-month sample) nmol cGMP/mu mol creatinine (mean +/- SEM, p < 0.02). Among the patients treated for cancer of the uterine corpus (n = 9), none showed recurrent disease within the observation Period of 10 years. The cGMP levels fell from 37.9 +/- 6.3 (baseline sample) to 22.3 +/- 2.3 (three-month sample) nmol cGMP/mu mol creatinine (p < 0.005). In the patients with ovarian cancer (n = 6), 4 patients relapsed during the observation period of 10 years. In these women the cGMP levels increased from 34.5 +/- 2.7 (baseline sample) to 46.3 +/- 4.7 nmol cGMP/mu mol creatinine whilst in both patients without relapse the levels decreased from 31.8 (range: 26.5-37.1) to 27.3 (range: 25.7-28.8) nmol cGMP/mu mol creatinine, respectively. The changes in levels of cAMP, CEA, CA-125 and PIINP did not show statistically significant differences. Early changes in cGMP levels appear to predict long-term prognosis in gynecological cancers.