Hyperprogressive Disease: Main Features and Key Controversies

Int J Mol Sci. 2021 Apr 3;22(7):3736. doi: 10.3390/ijms22073736.


Along with the positioning of immunotherapy as a preferential treatment for a wide variety of neoplasms, a new pattern of response consisting in a sudden acceleration of tumor growth has been described. This phenomenon has received the name of "hyperprogressive disease", and several definitions have been proposed for its identification, most of them relying on radiological criteria. However, due to the fact that the cellular and molecular mechanisms have not been elucidated yet, there is still some debate regarding whether this fast progression is induced by immunotherapy or only reflects the natural course of some highly aggressive neoplasms. Moreover, contradictory results of trials including patients with different cancer types suggest that both the incidence, the associated factors and the implications regarding prognosis might differ depending on tumor histology. This article intends to review the main publications regarding this matter and critically approach the most controversial aspects.

Keywords: cancer; checkpoint inhibitors; hyperprogressive disease; immunotherapy; solid tumors.

Publication types

  • Review

MeSH terms

  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunotherapy*
  • Neoplasms* / diagnosis
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Prognosis


  • Immune Checkpoint Inhibitors