Growth pattern and rate in residual nonfunctioning pituitary adenomas: correlations among tumor volume doubling time, patient age, and MIB-1 index

Object. Surgical cure can be achieved in pituitary adenomas when they are completely removed. It is controversial whether postoperative radiation therapy should be given to prevent recurrence, and whether an early reoperation should be performed for residual adenomas, because we have little information about the natural history of postoperative residual adenomas. Methods. The residual tumor volume was serially measured in 40 nonfunctioning pituitary adenomas (NFPAs) and the tumor volume doubling time (TVDT) was calculated. Correlations between the patients' age, tumor volume, log TVDT, and MIB-1 index were examined. Other factors including the patient's sex, cavernous sinus (CS) invasion by the tumor, or presence of an intratumoral cyst were analyzed to assess their influence on the TVDT. Values are expressed as the means +/- standard deviations. Thirty-eight adenomas increased in volume and two decreased during a follow-up period ranging from 4 to 141 months (mean 52.5 months). Exponentially linear tumor growth was observed in the 38 growing adenomas regardless of the residual tumor volume, with the TVDT ranging from 506 to 5378 days (mean 1836 days). The patients' age was 57.1 +/- 15.7 years (range 15-79 years), the tumor volume at the beginning of the magnetic resonance imaging observation period was 2.5 +/- 2.2 cm(3) (range 0.07-14.5 cm(3)), and the MIB-1 index was 0.73 +/- 0.68% (range 0.1-2.9%). There was a correlation between the log TVDT and patient age (R = 0.73), an inverse correlation between the log TVDT and MIB-1 index (r = -0.49), and an inverse correlation between the MIB-1 index and patient age (r = -0.61). A significant difference (p = 0.0001) was noted between the TVDT (1106 days) in the 19 patients younger than 61 years of age and the TVDT (2566 days) in the 19 patients who were 61 years of age or older. There was also a significant difference (p = 0.0002) between the age (50.8 +/- 15.3 years) of the patients with rapidly growing tumors (TVDT < 1836 days, 24 patients) and the age (69.1 +/- 7.6 years) of the patients with slowly growing tumors (TVDT > 1836 days, 14 patients). Other factors including the patients' sex, CS invasion, and intratumoral cyst formation did not affect the TVDT of residual NFPAs. Conclusions. The tumor growth rate of residual NFPAs is strongly influenced by the patient's age. The TVDT in elderly patients is much longer than that previously reported. Treatment strategies that take into consideration the natural history of residual adenomas should be established especially in the elderly population.