By Dr. Lagudu Perraju Bhaskar Bhuvan – Consultant Medical Oncologist at HCG Cancer Hospital, Vizag
“Stage IV.” “Metastatic.” “Palliative.” For decades, these were some of the most difficult words a patient or family could hear. They often signaled that cancer had spread beyond the point where surgery could help, and treatment was focused primarily on controlling symptoms and extending life for as long as possible.
Today, that landscape is changing.
Immunotherapy has emerged as one of the most significant advances in modern oncology, transforming outcomes for many patients with advanced cancers. Unlike chemotherapy or radiation, which attack cancer cells directly, immunotherapy works by empowering the body’s own immune system to recognize and eliminate cancer. For diseases once considered virtually untreatable, it is creating possibilities that seemed unimaginable just a decade ago.
Why Advanced Cancer Has Historically Been Difficult to Treat
Advanced or metastatic cancer occurs when cancer spreads from its original site to other parts of the body. For example, lung cancer may spread to the brain, melanoma to the liver, or colon cancer to the lungs.
Traditionally, treatment of metastatic disease faced several major challenges.
Firstly, cancer cells can develop resistance to chemotherapy. While chemotherapy may initially destroy many cancer cells, the more resistant cells often survive and continue growing, leading to disease progression.
Secondly, surgery and radiation have limitations when cancer has spread to multiple organs. Removing or irradiating numerous tumors throughout the body is often not feasible without causing significant damage to healthy tissue.
Thirdly, the treatments themselves can be difficult to tolerate. More intensive chemotherapy often brings greater toxicity, and many patients with advanced disease may not be physically strong enough to endure prolonged treatment.
How Immunotherapy Changes the Approach
The immune system constantly patrols the body, identifying and destroying abnormal cells. Cancer, however, develops sophisticated ways to evade detection.
Some tumors disguise themselves as normal tissue, making them difficult for immune cells to recognize. Others activate molecular pathways that effectively tell immune cells to stop attacking.
Immunotherapy helps overcome these defenses.
Checkpoint inhibitors, one of the most widely used forms of immunotherapy, block proteins such as PD-1, PD-L1, and CTLA-4 that act as “brakes” on immune cells. By releasing these brakes, T-cells can once again recognize and attack cancer.
Other innovative approaches include CAR-T cell therapy, in which a patient’s own immune cells are genetically engineered to target cancer more effectively before being returned to the body. Cancer vaccines are being developed to train the immune system to recognize tumor-specific mutations, while bispecific antibodies physically connect immune cells to cancer cells, enhancing the body’s ability to destroy tumors.
One of the most remarkable aspects of immunotherapy is the potential for immune memory. Even after treatment ends, the immune system may continue monitoring for cancer cells, helping maintain long-term disease control.
Cancers Where Immunotherapy Has Transformed Outcomes
Advanced Melanoma
Few cancers illustrate the impact of immunotherapy more dramatically than melanoma. Before 2011, treatment options were limited and long-term survival was rare.
Today, combination immunotherapy with nivolumab and ipilimumab has significantly improved outcomes, with more than half of treated patients alive at five years. A meaningful proportion remain cancer-free even a decade after treatment, raising the possibility of long-term remission and, in some cases, cure.
Metastatic Non-Small Cell Lung Cancer
Historically, patients with advanced lung cancer survived an average of only several months following diagnosis.
The introduction of pembrolizumab and other checkpoint inhibitors has dramatically improved outcomes. For selected patients, immunotherapy can produce durable responses lasting years, and some patients are able to discontinue treatment while maintaining disease control.
Advanced Kidney Cancer
Renal cell carcinoma was once managed primarily with targeted therapies that could slow disease progression but rarely produced lasting remissions.
Immunotherapy combinations such as nivolumab and ipilimumab have significantly improved long-term survival, offering many patients more durable disease control and improved quality of life.
Bladder, Head and Neck, and MSI-High Cancers
Certain tumors carry defects in their DNA repair systems, known as microsatellite instability-high (MSI-high) or mismatch repair deficiency (dMMR).
These cancers often respond exceptionally well to immunotherapy. In recognition of this, immunotherapy became the first cancer treatment approved based on a tumor’s genetic characteristics rather than its organ of origin—a major milestone in precision oncology.
Blood Cancers
CAR-T cell therapy has produced remarkable results in certain leukemias and lymphomas that have relapsed after conventional treatment. In some patients who had exhausted all available options, CAR-T therapy has induced deep and lasting remissions, earning its reputation as a “living drug.”
A Breakthrough, Not a Universal Cure
Despite its promise, immunotherapy is not effective for every patient.
Response rates vary considerably between cancer types, and many patients do not benefit from immunotherapy alone. Biomarkers such as PD-L1 expression, MSI status, and tumor mutational burden (TMB) help oncologists identify those most likely to respond.
Immunotherapy can also cause unique side effects. Because it activates the immune system, it may trigger inflammation in healthy organs including the skin, lungs, intestines, thyroid gland, and liver. Most reactions are manageable when recognized early, but some can be serious and require specialized care.
Cost and accessibility remain additional challenges. While checkpoint inhibitors and CAR-T therapies can be expensive, increasing availability of biosimilars, patient assistance programs, and indigenous innovations such as NexCAR19 are helping expand access in India.
Researchers are also working to improve outcomes in so-called “cold tumors” such as pancreatic, prostate, and certain brain cancers, which are less visible to the immune system and therefore less responsive to current immunotherapy approaches.
What Treatment Looks Like Today
The treatment journey for advanced cancer patients has evolved significantly.
Instead of automatically beginning chemotherapy, many patients now undergo biomarker testing to determine whether immunotherapy, targeted therapy, chemotherapy, or a combination approach is most appropriate.
Most checkpoint inhibitors are administered as outpatient infusions every few weeks, often requiring shorter hospital visits and causing fewer traditional chemotherapy-related side effects such as hair loss.
Equally important, patients are educated to recognize and report symptoms early so that immune-related side effects can be managed promptly.
For many individuals, treatment goals have shifted from measuring survival in months to measuring survival in years. Long-term disease control is no longer an exception—it is an increasingly realistic possibility for selected patients.
The Future of Immunotherapy
The next generation of immunotherapy aims to help more patients benefit from these advances.
Researchers are exploring combinations of immunotherapy with chemotherapy, radiation, and targeted therapies. These approaches may help convert resistant tumors into ones that are more vulnerable to immune attack.
Immunotherapy is also being introduced earlier in the treatment journey, including before surgery in selected cancers, where it may improve cure rates and reduce the risk of recurrence.
Perhaps most exciting is the development of personalized cancer vaccines. Using technologies such as mRNA, these vaccines are designed around the unique genetic mutations within an individual’s tumor, potentially enabling highly customized immune responses.
The Bottom Line
A decade ago, advanced cancer and hope rarely appeared in the same conversation.
Today, immunotherapy has fundamentally changed that reality.
It has not replaced surgery, chemotherapy, radiation, or targeted therapy. Instead, it has become a powerful new pillar of cancer treatment, offering many patients longer survival, better quality of life, and in some cases, durable remission that was once considered impossible.
For patients facing advanced cancer, immunotherapy represents more than a new treatment option. It represents a new way of thinking about what is possible.