Dr. Niegisch notes that there is proven efficacy of chemotherapy in the perioperative setting. Meta-analytic hazard ratios for neoadjuvant chemotherapy show that there is a survival benefit in this setting by improving oncological outcomes (HR 0.86, 95% CI 0.75-0.98), whereas adjuvant chemotherapy probably improves oncologic outcomes (HR 0.74, 95% CI 0.55-0.99). On the contrary, phase III trials of neoadjuvant immunotherapy are still pending with regards to survival benefit. In the adjuvant setting, as first presented at ASCO 2020, the IMvigor 010 trial showed no survival benefit for patients receiving adjuvant atezolizumab vs observation (DFS HR 0.89, 95% CI 0.74-1.08). Thus, according to Dr. Niegisch, the survival advantage of immunotherapy over chemotherapy is still to be shown. When looking at oncological surrogates, such as downstaging and pathologic complete response, the response rates of chemotherapy are in fact comparable to immunotherapy: 
With regards to toxicity and adverse events, PURE-01 had 3% of patients with >= grade 3 adverse events, whereas ABACUS had 11% of patients. This is much more favorable compared to chemotherapy whereby >= grade 3 adverse events are seen in up to 80% of patients, most commonly anemia, leukopenia, and thrombocytopenia. As such, >= grade 3 toxicities are less frequent when using immunotherapy monotherapy compared to chemotherapy. To summarize, survival outcomes of immunotherapy are unclear, there are comparable pathologic complete response rates to chemotherapy, as well as comparable downstaging rates. However, immunotherapy is better tolerated, with less frequent toxicity when used in the monotherapy setting. So, according to Dr. Niegisch, replacing perioperative chemotherapy with immunotherapy at this point is not justified. In his opinion, the better question is “should we improve perioperative systemic therapy by the use of immune checkpoint inhibitors?” He notes that 25-50% of patients who may benefit from neoadjuvant chemotherapy do not get a chance to benefit. Furthermore, those that do not respond to neoadjuvant chemotherapy (ypT2-T4) do poorly, with worse cancer-specific survival than those that did not even receive neoadjuvant chemotherapy. Given that downstaging rates for both chemotherapy and immunotherapy range from ~40%-55%, there is room for improvement for both chemotherapy and immunotherapy in this setting. Ultimately, this is the opportunity of biomarkers to correctly select patients for therapy.
Dr. Niegisch concluded his presentation with the following conclusions:
- Perioperative chemotherapy does improve oncological outcomes in terms of overall survival (neoadjuvant for sure, adjuvant probably)
- Pathologic complete response and downstaging rates following immunotherapy are comparable to chemotherapy
- High-grade toxicities of chemotherapy are more frequent but manageable
- The current data does not support replacing perioperative chemotherapy by immunotherapy, but rather points towards searching for more individualized treatment approaches
Presented by: Gunter Niegisch, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md at the Virtual 2020 EAU Annual Meeting #EAU20, July 17-19, 2020.