Immunotherapy pseudo progression
Can your tumour get bigger before it gets smaller during treatment? Dr Ronwyn van Eeden explains the pseudo progression phenomenon.
Immunotherapy has revolutionised cancer treatment over the past few years by leading to significant overall survival benefits in patients with advanced cancer. Immunotherapy works by activating the body’s own immune system to fight cancer.
Unlike conventional therapies, such as chemotherapy, that cause shrinkage of tumours or cancer cells, because of the unique way in which immunotherapy works it can cause a different or atypical kind of response in cancer cells.
Pseudo progression is one of these atypical responses. The exact mechanism by which it occurs is still unclear. It’s potentially from an influx of immune cells that accumulate around the tumour which can cause inflammation or oedema (swelling) around the cancer. It’s a phenomenon which can possibly cause an initial increase in the size of the tumour before it shrinks. Occasionally, it can also cause new tumours areas to appear and then disappear.
The problem with not being aware of this phenomenon, is that it can lead to premature stopping or discontinuation of immunotherapy treatment under the pretence that things are getting worse and not better.
According to the data available, which is retrospective, the incidence of pseudo progression is 2-10% which isn’t that common. Some studies show an incidence of up to 20%.
The incidence may vary depending on the cancer type and biological characteristics of the tumour or even the type of immunotherapy used. The decision when to stop immunotherapy treatment is of course at the discretion of the treating oncologist but can often be very challenging.
The clinical picture of the patient is an important consideration when making this decision. If the radiological investigation, such as a CT scan, shows an increase in size of the tumour in the case of pseudo progression, the patient is usually simultaneously very well, without any new symptoms, and their clinical condition will be improving as well.
If the patient, in the presence of growth of the cancer or presence of new tumours, looks very ill or their clinical condition is deteriorating, then it could be true or actual progression of cancer. The oncologist can decide to change treatment at this point. Sometimes if the oncologist is unsure, a biopsy of the new or enlarging tumour can be requested.
Research is ongoing to find other ways to distinguish the difference between true progression and pseudo progression, such as different kinds of imaging techniques or blood tests, to check circulating tumour DNA or inflammatory marker levels in the blood. These aren’t established yet. Some research suggests that if patients have pseudo progression it could translate into a better survival as well.
When patients are on immunotherapy and pseudo progression is suspected, immunotherapy treatment should be continued, and a repeat scan should be done in about four to eight weeks. If the repeat scan shows the tumours are still increasing in size, it can safely be said then only that the treatment isn’t working.
The radiologists that are reporting the scans for patients on immunotherapy also have to be trained on how to do this kind of reporting correctly. A new criteria has been developed for the use of these scan reports; called immune-related response criteria (irRC, iRECIST) and immune-modified response evaluation criteria in solid tumours (imRECIST). The radiologist takes into consideration the fact the patient is on immunotherapy if something has grown or something new appears and will use the term: unconfirmed progressive disease (iUPD) and suggest a repeat scan. If there is still progression, after four to eight weeks, the radiologist will report confirmed progressive disease (iCPD).
Another type of atypical response to immunotherapy is called hyper progression. This refers to accelerated tumour progression and rapid deterioration in the patient’s cancer while on immunotherapy. This is very rare but can have negative implications for patients and usually indicates a poorer prognosis. This can occur in up to 13% of patients on immunotherapy. There seems to be certain risk factors associated with this, such as older age, being female and harbouring certain types of mutations.
Occasionally, there can be mixed responses as well, where some tumours are getting smaller while others are increasing in size. Mostly, immunotherapy will cause the reduction of growth or shrinkage of cancers but patterns of response to immunotherapy can be quite complicated. The awareness of these atypical responses is important so that the correct treatment decisions are made, and treatment isn’t stopped too quickly or continued unnecessarily.
There is still a lot of research that needs to be conducted to perfect the correct clinical applications for patients on immunotherapy and to correctly identify what type of response a patient is having.
- Wenxiao et al. Cancer Biol Med. 2019
- Yiming et al. Am J Cancer Res. 2019
- Kartiok et al. Jama Networkopen 2021
MEET THE EXPERT – Dr Ronwyn van Eeden
Dr Ronwyn van Eeden is a medical oncologist in private practice in Rosebank, Gauging. She is also an honorary consultant in oncology at the Chris Hani Baragwanath Hospital.
Image by stock.adobe.com