Context: Data on the association between growth hormone (GH) replacement in patients with GH deficiency (GHD) after malignancies and new neoplasms show conflicting results.

Objective: To clarify the incidence of new malignant neoplasm in childhood-onset (CO) and adult-onset (AO) adult cancer survivors (CSs).

Design: Retrospective comparison of CO-CS and AO-CS with CO idiopathic GHD (IGHD) and AO nonfunctioning pituitary adenoma (NFPA) patients and with the general population [standardized incidence ratio (SIR)].

Setting: Data from the Pfizer International Metabolic Database study (KIMS).

Patients: CO-CS [n = 349; 50.4% females; mean baseline (MBL) IGF-I standard deviation score (SDS), -2.4], IGHD (n = 619; 35.7% females; MBL IGF-I SDS, -3.4), AO-CS (n = 174; 42.5% females; MBL IGF-I SDS, -1.4), and NFPA (n = 2449; 38.1% females; MBL IGF-I SDS, -1.0).

Main Outcome Measures: SIRs of malignant neoplasms.

Results: After a median follow-up of 5.9 years (2192 patient-years), 15 CO-CS (4.3%) had developed 16 new neoplasms. The SIR was 10.4 [95% confidence interval (CI), 5.9 to 16.9] and 6.5 (95% CI, 3.0 to 12.4) after exclusion of seven patients with skin cancers. In IGHD, three malignant neoplasms (0.5%) were observed after a median follow-up of 5.4 years (3908 patient-years; SIR, 0.47; 95% CI, 0.09 to 1.37). New malignant neoplasms occurred in three AO-CS (1.7%; SIR, 1.1; 95% CI, 0.2 to 3.2) and 146 NFPA patients (153 cases, 6.0%; SIR, 1.1; 95% CI, 0.9 to 1.2) after a median follow-up of 4.9 (1024 patient-years) and 5.6 years (15,215 patient-years).

Conclusions: The risk of second malignant neoplasms was increased in CO-CS but not in AO-CS, which illustrates the need to closely follow patients on GH replacement because of a prior malignancy.