How Immunotherapy Before Surgery Can Impact Patient Outcomes

For some cancer patients, immunotherapy can serve as a first-line treatment, while for others it can act as an alternative to prior treatments that have proved unsuccessful. Scientists sometimes treat patients with immunotherapy before surgery in a comprehensive effort to treat cancer. 

We will continue to learn how to best apply immunotherapy around the time of surgery for many years to come.

Haydn Kissick, PhD, CRI Lloyd J. Old STAR

Treating cancer often involves multiple different strategies that include surgery, chemotherapy, radiotherapy, and immunotherapy. Conventionally, combination therapies like chemotherapy or immunotherapy are given after the patient has undergone surgery for the cancer. This approach is called adjuvant therapy, with the general idea that the majority of tumor is first removed by surgery and subsequent chemotherapy, or immunotherapy is a failsafe mechanism to eliminate any leftover cancer cells. 

However, there are cases where surgical removal of the tumor is not possible, the patients have had limited therapy options including radiation therapy and chemotherapy.  

When surgery is used as the first line of treatment along with adjuvant therapy, the patient outcomes have been mostly encouraging, however the chance of relapse is still a big concern for these patients. 

CRI-Funded Scientist Offers a Nuanced Perspective 

In recent years, a growing amount of research led by CRI scientists has demonstrated newfound successes in patient outcomes when healthcare teams implement immunotherapy treatment prior to performing surgery. While some promising results show that there is a wide range of cancers that can be thwarted with this treatment combination, which is also known as neoadjuvant therapy, one CRI-funded scientist provided a distinct view.

Haydn Kissick, PhD, assistant professor in the Department of Urology with a joint appointment in the Department of Microbiology and Immunology at the Emory University School of Medicine, member of the Cancer Immunology Research Program at Winship Cancer Institute, member of the Emory Vaccine Center, and CRI Lloyd J. Old STAR, recently spoke with CRI and conveyed that this is a nuanced subject.

“Immunotherapy seems to have a place to provide benefits for patients with a disease that has some features that make it a high risk of returning after surgery,” Dr. Kissick said. “In several cancers there is a small benefit of preventing the disease coming back, but we do not know which patient will benefit or who might have bad side effects and would have been cured by just the surgery alone. The future goal is for us to have molecular markers of a patient’s tumor that can help us make this decision with more information.” 

He elaborated that the spectrum of cancer types varies in predictability regarding outcomes with immunotherapy before surgery. Dr. Kissick provided his input alongside two of his colleagues at Emory University: Asim Bilen, MD, medical oncologist; and Viraj Master, MD, PhD, FACS, surgical oncologist. 

“For kidney cancer, the field is still unsure. There is recent data on patients with advanced kidney cancer having some benefit from immunotherapy if given right after surgery, but similar patients did not see any benefit,” he said alongside the two oncologists. Other cancers, like melanoma, provide greater clarity – if a patient received checkpoint immunotherapy before surgery, the outcome is better than if surgery had come first. “We have no good understanding why this occurs, or if similar effects might occur in other cancers.”

CRI-Affiliated Scientists Reveal Positive Results from Recent Research

Research published in June 2024 on colorectal cancer illustrated that a pre-surgery immunotherapy combination met successful safety standards. Ton Schumacher, PhD, deputy director of the Netherlands Cancer Institute in Amsterdam, professor of immuno-technology at Leiden University Medical Center, and CRI Scientific Advisory Council member, contributed towards this impactful new research.

In March of 2023, research revealed positive results for patients who have received a combination immunotherapy-chemotherapy treatment for early stage, resectable non-small cell lung cancer (NSCLC) before undergoing surgery. The phase II results documented in the study concluded that dual immune checkpoint therapy and chemotherapy produced higher major pathological response rates, is safe, and enhances anti-tumor activity before surgery. Additionally, results were better for patients in the study who took immunotherapy before undergoing surgery. Three CRI-affiliated scientists contributed to this study:

1. Jennifer Wargo, MD, professor of surgical oncology and genomic medicine, leader of the Platform for Innovative Microbiome and Translational Research (PRIME-TR) of the University of Texas MD Anderson Cancer Center, and CRI Scientific Advisory Council member.

2. James Allison, PhD, chair of immunology, the executive director of the Immunotherapy Platform, deputy director for Applied Research of Genitourinary Cancers at the University of Texas MD Anderson Cancer Center, National Cancer Moonshot Blue Ribbon Panel member, Nobel laureate, and CRI Scientific Advisory Council director.

3. Padmanee Sharma, MD, PhD, professor in the departments of Genitourinary Medical Oncology and Immunology, scientific director for the Immunotherapy Platform at the University of Texas MD Anderson Cancer Center, co-director of the Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center, and CRI Scientific Advisory Council member. 

CRI continues to communicate neoadjuvant immunotherapy progress with its community through research and other written content, but also at conferences and other public-facing events. Sarah Sammons, MD, the associate director of the Metastatic Breast Cancer Program at the Dana-Farber Cancer Institute, spoke about neoadjuvant surgery’s success rate at the CRI Patient Immunotherapy Summit 2023/2024. Regarding breast cancer, Dr. Sammons stressed that patients with stage II or III triple negative breast cancer experience optimal outcomes when they receive immunotherapy-chemotherapy treatment before surgery. 

“A lot of people diagnosed with breast cancer say, ‘I want this thing out of me, get me to surgery,’” Dr. Sammon said. “When the cancer cells go away at the time of surgery, those patients have about a 93 to 94 percent chance of being cured of their cancer.”

Immunotherapy before surgery is a subject that immunologists will continue to investigate. It is not a cut-and-dry issue, but there is also some recent evidence for continued progress as we strive towards creating a world immune to cancer.