Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy.
The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality.
Over a median clinical follow-up of 8.4 years, there were 64 (9.7%) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5–6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95% CI 1.4–14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR.
Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.
Abbreviations used in this paper: ACTH = adrenocorticotropic hormone; CI = confidence interval; CT = computed tomography; GH = growth hormone; GTR = gross-total resection; HR = hazard ratio; MR = magnetic resonance; NDI = National Death Index; NFPA = nonfunctional pituitary adenoma; OR = odds ratio; SSDI = Social Security Death Index; STR = subtotal resection.
Address correspondence to: Edward F. Chang, M.D., Department of Neurological Surgery, University of California, San Francisco, 505 Parnassus Avenue, M779 Campus Box 0122, San Francisco, California 94143. email:
BarkerFGIIKlibanskiASwearingenB: Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab88:4709–47192003
BradleyKJWassJATurnerHE: Non-functioning pituitary adenomas with positive immunoreactivity for ACTH behave more aggressively than ACTH immunonegative tumours but do not recur more frequently. Clin Endocrinol (Oxf)58:59–642003
BradleyKMAdamsCBPotterCPWheelerDWAnslowPJBurkeCW: An audit of selected patients with non-functioning pituitary adenoma treated by transsphenoidal surgery without irradiation. Clin Endocrinol (Oxf)41:655–6591994
HardyJTranssphenoidal surgery of hypersecreting pituitary tumors. KohlerPORossGT: Diagnosis and Treatment of Pituitary Tumors. International Congress SeriesVol 303:AmsterdamExcerpta Medica1973. 179–198
McColloughWMMarcusRBJrRhotonALJrBallingerWEMillionRR: Long-term follow-up of radiotherapy for pituitary adenoma: the absence of late recurrence after greater than or equal to 4500 cGy. Int J Radiat Oncol Biol Phys21:607–6141991
MinnitiGTraishDAshleySGonsalvesABradaM: Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years. J Clin Endocrinol Metab90:800–8042005
SheehanJPNiranjanASheehanJMJaneJAJrLawsERKondziolkaD: Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium. J Neurosurg102:678–6912005
ZadaGKellyDFCohanPWangCSwerdloffR: Endonasal transsphenoidal approach for pituitary adenomas and other sellar lesions: an assessment of efficacy, safety, and patient impressions. J Neurosurg98:350–3582003