Pseudoprogression and hyperprogression in lung cancer: a comprehensive review of literature

J Cancer Res Clin Oncol. 2020 Dec;146(12):3269-3279. doi: 10.1007/s00432-020-03360-1. Epub 2020 Aug 28.


Purpose: Immune checkpoint inhibitors are associated with clinical benefit in lung cancer. However, response patterns to immunotherapy, including pseudoprogression and hyperprogression, are difficult to diagnose, and their mechanisms remain unclear. This review aimed to describe two response patterns observed in lung cancer, namely pseudoprogression and hyperprogression, including their epidemiology, diagnostic characteristics, and plausible mechanisms.

Methods: We performed a comprehensive literature search in the PubMed database, using keywords "pseudoprogression", "hyperprogression", and "lung cancer", among others. The literature was examined for pseudoprogression and hyperprogression characteristics and plausible mechanisms.

Results: Pseudoprogression manifests in multiple forms; however, the immune system-related response criteria and biopsy data are helpful to make accurate diagnosis. Serological biomarkers, such as neutrophil-to-lymphocyte ratio (NLR) and circulating tumor DNA (ctDNA), might help distinguish pseudoprogression from true progression. The incidence of hyperprogression ranges within 5-19.2%, depending on definition. The unique response pattern of rapid progression is observed not only with immunotherapy, but also with other treatment regimens. Molecular mutations and amplifications may result in hyperprogression; however, the exact mechanism remains unclear.

Conclusion: Atypical response patterns, such as pseudoprogression and hyperprogression, are increasingly common in clinical practice. Immune-related response criteria can help diagnose pseudoprogression. Molecular mechanisms of hyperprogression remain unclear. Biomarkers for pseudoprogression and hyperprogression are required.

Keywords: Hyperprogression; Immunotherapy; Lung cancer; Pseudoprogression.

Publication types

  • Review

MeSH terms

  • Circulating Tumor DNA / blood
  • Disease Progression*
  • Humans
  • Immunologic Factors / immunology*
  • Lung Neoplasms / blood
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lymphocytes / pathology
  • Neutrophils / pathology
  • Response Evaluation Criteria in Solid Tumors


  • Circulating Tumor DNA
  • Immunologic Factors