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Grading system may predict recurrence, progression of pituitary neuroendocrine tumors
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The risk for recurrence or progression of pituitary neuroendocrine tumors in adults is significantly associated with age and tumor type, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
Gérald Raverot, MD, PhD, of Hospices Civils de Lyon, Federation d'Endocrinologie du Pole Est in France, and colleagues evaluated 374 adults (194 women) who underwent surgery for a pituitary neuroendocrine tumor (mean age at surgery, 51.9 years) between February 2007 and October 2012 to test the value of a new classification system on prognostic relevance.
Tumors were classified using a grading system based on invasion on MRI, immunocytochemical profile, Ki-67 mitotic index and p53 positivity. Noninvasive tumors were classified as grade 1a, noninvasive but proliferative tumors were grade 1b, invasive tumors were grade 2a, invasive and proliferative tumors were grade 2b and metastatic tumors were grade 3.
Macroadenomas were the most common type of tumor based on MRI classification (82.1%), followed by microadenoma (13.6%) and giant adenoma (4.3%).
Information on grade was available for 365 tumors; grade 1a was the most common (51.2%), followed by grades 2a (32.3%), 2b (8.8%) and 1b (7.7%).
The progression-free survival analysis included 213 participants from the original cohort during a mean follow-up of 3.5 years. A recurrent event occurred in 52 participants, and progression occurred in 37 participants. The risk for recurrence and/or progression was associated with age (P = .035), tumor type (P = .028) and grade (P < .001). The risk for recurrence and/or progression was increased with grade 2b tumors compared with grade 1a tumors (HR = 3.72; 95% CI, 1.9-7.26) regardless of tumor type. Invasion was significantly associated with recurrence in grade 2a tumors (HR = 2.98; 95% CI, 1.89-4.7), whereas proliferation was not significantly associated with prognosis for grade 1b (HR = 1.25; 95% CI, 0.73-2.13).
“This prospective study confirms the usefulness of our previously proposed classification and may now allow clinicians to adapt their therapeutic strategies according to prognosis, but may also be used to stratify patients and evaluate therapeutic efficacy in future clinical trials,” the researchers wrote. “Further progress can be expected, in particular if an improved understanding of molecular abnormalities associated with pituitary tumorigenesis generates better biomarkers.” – by Amber Cox
Disclosures: The researchers report no relevant financial disclosures.
Perspective
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“Everything is vague to a degree you do not realize, till you have tried to make it precise.” This quote by Bertrand Russell comes to mind when one thinks of the many attempts over the years to stratify pituitary adenomas for their clinical behavior and, consequently, their risk of recurrence. The vagueness of their behavior stems from the fact that pituitary adenomas are “benign” tumors histologically. The fact that pituitary adenomas do not metastasize, however, does not mean that they behave like any other benign overgrowth of the human body: Pituitary adenomas often recur, and when not cured surgically, or by other means, they affect tremendously the patients’ quality of life, being frequently the cause of significant morbidity and even mortality. This is why the study by Raverot and colleagues adds significantly to the field by attempting to “make precise” the business of predicting which pituitary adenoma is at high risk for early recurrence or progression.
The authors used a previously developed model of using Ki-67, p53 positivity, mitotic index and other immunocytochemical profile, in addition to MRI, to prospectively evaluate the risk for recurrence or progression. A total of 365 tumors were graded in one of five grades for 374 patients over a mean length of follow-up of 3.5 years. The tumors that were graded the highest score (grade 2b) had a 3.7-fold increased risk of recurrence or progression compared with tumors that were graded the lowest (grade 1a). Despite its relatively short average follow-up time, the study offers a systematic approach to evaluating risk for recurrence or progression for pituitary adenomas. In addition, it utilizes markers that are widely in use, making it feasible to obtain outside highly specialized centers. It remains to be seen whether it is also useful in predicting response to treatment for recurrent pituitary adenomas; the field is in dire need for such prognostication.
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