Incidence of primary cancers and intracranial tumour recurrences in GH-treated and untreated adult hypopituitary patients: analyses from the Hypopituitary Control and Complications Study

Abstract

Objective: Speculation remains that GH treatment is associated with increased neoplasia risk. Studies in GH-treated childhood cancer survivors suggested higher rates of second neoplasms, while cancer risk data for GH-treated and untreated hypopituitary adults have been variable. We present primary cancer risk data from the Hypopituitary Control and Complications Study (HypoCCS) with a focus on specific cancers, and assessment of recurrence rates for pituitary adenomas (PA) and craniopharyngiomas (CP). Design: Incident neoplasms during HypoCCS were evaluated in 8418 GH-treated vs 1268 untreated patients for primary malignancies, 3668 GH-treated vs 720 untreated patients with PA history, and 956 GH-treated vs 102 untreated patients with CP history. Methods: Using population cancer rates, standardised incidence ratios (SIRs) were calculated for all primary cancers, breast, prostate, and colorectal cancers. Neoplasm rates in GH-treated vs untreated patients were analysed after propensity score adjustment of baseline treatment group imbalances. Results: During mean follow-up of 4.8 years, 225 primary cancers were identified in GH-treated patients, with SIR of 0.82 (95% CI 0.71-0.93). SIRs (95% CI) for GH-treated patients were 0.59 (0.36-0.90) for breast, 0.80 (0.57-1.10) for prostate, and 0.62 (0.38-0.96) for colorectal cancers. Cancer risk was not statistically different between GH-treated and untreated patients (relative risk (RR)Z1.00 (95% CI 0.70-1.41), PZ0.98). Adjusted RR for recurrence was 0.91 (0.68-1.22), PZ0.53 for PA and 1.32 (0.53-3.31), PZ0.55 for CP. Conclusions: There was no increased risk for all-site cancers: breast, prostate or colorectal primary cancers in GH-treated patients during HypoCCS. GH treatment did not increase the risk of PA and CP recurrences.

Long‐term safety of growth hormone—A combined registry analysis

“…Later reports from HypoCCS, with longer duration of follow-up, confirmed these earlier results 24,34,42 and showed no increase in all-site cancers: breast, prostate or colorectal primary cancers, or in the recurrence rates for pituitary adenomas or craniopharyngiomas. 42 In KIMS, no relationship between relapse of intracranial germ cell tumours and GH replacement was shown. 46,47 The risk of a second neoplasm in childhood cancer survivors was evaluated using data from GeNeSIS and HypoCCS.…”

“…However, elevated SIRs were shown for patients aged <35 years and for those patients diagnosed with CO‐GHD, which may be related to an increased risk among survivors of childhood neoplastic disease. Later reports from HypoCCS, with longer duration of follow‐up, confirmed these earlier results and showed no increase in all‐site cancers: breast, prostate or colorectal primary cancers, or in the recurrence rates for pituitary adenomas or craniopharyngiomas . In KIMS, no relationship between relapse of intracranial germ cell tumours and GH replacement was shown .…”

“…Data from the HypoCCs and KIMS databases on recurrence of pituitary adenoma or craniopharyngioma in GH‐treated adults revealed no significant differences in relative risk of recurrence between GH‐treated and untreated patients. However, as these types of tumours are slow‐growing, the follow‐up period in both studies may not have been adequate to verify the absolute risk of GH treatment on tumour recurrence.…”

“…The risk of primary or secondary cancers has been evaluated in children enrolled in GeNeSIS, KIGS and NCGS, and in adults enrolled in HypoCCS and KIMS (summarized in Table ). Among 19 054 GH‐treated children without a history of malignancy in GeNeSIS, all‐site primary cancer risk during a mean follow‐up period of 3.4 years was similar to that in the general population of cancer registries .…”

“…The risk of primary or secondary cancers has been evaluated in children enrolled in GeNeSIS, [41][42][43][44] and NCGS, 20 and in adults enrolled in HypoCCS 24,34,41,42,44 and KIMS 46 (summarized in Table 3).…”