Athens, Greece (UroToday.com) Dr. Andrea Necchi began the debate in this session supporting the role of immunotherapy over chemotherapy as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC).
According to the EAU guidelines, neoadjuvant immunotherapy to patients should only be given in the setting of a clinical trial, while chemotherapy is recommended as the standard of care, being the only suggested option of neoadjuvant chemotherapy.
In other cancers, there have been examples of the role of effective immunotherapy in the neoadjuvant setting. These cancers include melanoma, non-small cell lung carcinoma, and glioblastoma. In MIBC cisplatin-based chemotherapy is regarded as the standard of care. However, there are some important limitations for the use of chemotherapy in this setting:
- Real world adherence to neoadjuvant chemotherapy are quite low
- 50% of patients cannot receive cisplatin due to various reasons and many refuse
- The selection criteria for neoadjuvant chemotherapy are based on clinical staging which harbors great heterogeneity and is far from accurate
There have been several investigator-initiated neoadjuvant trials of immune checkpoint blockade before radical cystectomy (Table 1). There are many more ongoing immunotherapy neoadjuvant trials (Table 2) which will show their results in the upcoming years.
Table 1- Immunotherapy trials assessing its role in the neoadjuvant setting:
Table 2 -Ongoing immunotherapy neoadjuvant trial in bladder cancer:
Dr. Necchi has previously attempted to assess if the tumor mutational burden was the key predictor of immunotherapy efficacy in MIBC. In an interesting study, he tried to compare the baseline molecular alterations identified in patient responder subgroups (112 patients with evaluable TURBT samples) (Table 3).
Table 3 – Comparison of baseline molecular alterations identified in pT responder subgroups (n=112):
There has been some work done attempting to predict response and survival after neoadjuvant chemotherapy and after neoadjuvant immunotherapy. The following parameters were assessed to see if they can affect the response rate and survival after neoadjuvant immunotherapy (Table 3).
This is one of the reasons for the development of the molecular subtypes of bladder cancer, providing us data on which subtypes respond better to certain treatments (Table 4). It is still not clear if intrinsic subtype or immune infiltration informs a pathological response to immunotherapy.
It has also been shown that gene expression-based immune signatures may have enough signal for predicting pathological response to pembrolizumab, but more validation work is needed.
Table 3 – Can we predict response and survival after neoadjuvant immunotherapy, using these parameters?
In conclusion, in MIBC pathologic response rates observed in single agent immunotherapy studies are quite promising. There is a need to confirm the association with long-term improved outcomes. Biomarker-based trials of bladder preservation without aggressive local therapies can change the clinical practice. Future strategies will require biomarker use for patient’s selection. Lastly, the immune-gene signature may allow discriminating against the activity of neoadjuvant pembrolizumab from that of neoadjuvant chemotherapy.
Table 4 – Bladder cancer molecular subtypes and responses:
Presented by: Andrea Necchi, MD, medical oncologist at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, USA, Twitter: @GoldbergHanan at the 39th Congress of the Société Internationale d'Urologie, SIU 2019, #SIUWorld #SIU2019, October 17-20, 2019, Athens, Greece