Challenges and Gaps in the Management of Aggressive Pituitary Tumours: A Narrative Review

An Aggressive Pituitary Tumour (APT) is defined as a tumour showing unusually rapid tumour growth with invasion into surrounding structures evidenced on imaging, or clinically relevant tumour growth despite optimal standard therapies. Almost all of APTs are macroadenomas at clinical presentation accounting for up to 15% of all pituitary neoplasms. No single marker can accurately predict the behaviour of a tumour. Ki-67 index >3%, mitotic count >2 mitoses per 10 HPF and the presence of p53 expression along with imaging showing features of invasion have been the most reliable diagnostic methods. Intrinsic characteristics of the tumour determine the rapidity of tumour growth rate of recurrence and the degree of resistance to conventional treatments. Invasiveness is a major determinant of incomplete tumour resection. APTs are resistant to current available treatment options including surgery, standard medical therapy, and radiotherapy. Multimodal approach in the management comprises re-do surgery, with medical therapy including chemotherapy and radiotherapy. Temozolomide, a chemotherapeutic agent can be used in those with documented tumour growth despite optimal standard therapy. Though medical therapy alone is not effective in controlling tumour growth in APT; it helps in controlling hormone hypersecretion to some extent. Peptide receptor radionuclide therapy (PRRT), targeted therapies and immune checkpoint inhibitors are emerging treatment modalities. Lifelong follow up is required with periodic imaging and hormonal evaluation to assess treatment response, adverse effects of medications and evolution to pituitary carcinoma. Future studies are needed to identify prognostic indicators of future aggressive behaviour of pituitary tumours and biomarkers to assess treatment response.