Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas

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  • 1 Departments of Neurological Surgery
  • 4 Biostatistics, and
  • 6 Medicine, Division of Endocrinology, University of California, San Francisco;
  • 2 Department of Neurological Surgery, University of Southern California, Los Angeles, California;
  • 3 Department of Medicine, Harvard Medical School, Boston, Massachusetts; and
  • 5 Department of Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Object

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.

Methods

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.

Results

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.

Conclusions

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.

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Contributor Notes

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: echang@itsa.ucsf.edu.
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