Hopkins: Pre-Surgery Immunotherapy Success
A Johns Hopkins trial found that immunotherapy before and after surgery extended median survival to 28.6 months, 10 months longer than average.
Key Findings
| Metric | Result |
|---|---|
| Median overall survival | 28.6 months |
| Average mesothelioma survival | 18 months |
| Survival improvement | +10.6 months (59%) |
| Patients completing surgery | 80%+ |
| Recurrence-free at follow-up | 36% |
A first-of-its-kind clinical trial from Johns Hopkins has demonstrated that combining immunotherapy before and after surgery can extend mesothelioma survival by nearly 60% compared to historical averages. The results, published in Nature Medicine in September 2025, offer new hope for patients with operable disease.
The Trial Design
The phase 2 trial, designed by Joshua Reuss, M.D. during his fellowship at the Johns Hopkins Kimmel Cancer Center, tested a novel approach: giving immunotherapy both before (neoadjuvant) and after (adjuvant) surgical removal of mesothelioma tumors.
Treatment Protocol
Patients received:
- Neoadjuvant phase: Nivolumab plus ipilimumab before surgery
- Surgery: Pleurectomy/decortication or extrapleural pneumonectomy
- Adjuvant phase: Continued immunotherapy after recovery
This “sandwich” approach aims to shrink tumors before surgery, then eliminate any remaining cancer cells afterward.
Survival Results
The combination immunotherapy arm achieved remarkable outcomes:
| Outcome | Combination (Nivo+Ipi) | Historical Average |
|---|---|---|
| Median overall survival | 28.6 months | 18 months |
| Alive and recurrence-free | 36% | ~15% |
| Surgical completion rate | >80% | Variable |
The 28.6-month median survival represents a 59% improvement over the typical 18-month survival for people with mesothelioma.
Liquid Biopsy Breakthrough
Perhaps equally important, the trial demonstrated that circulating tumor DNA (ctDNA) testing, a type of “liquid biopsy”, could predict which patients would benefit most.
ctDNA Findings
- Patients with undetectable ctDNA after neoadjuvant treatment had significantly longer survival
- A 95%+ drop in ctDNA during treatment predicted better outcomes
- Persistent ctDNA signaled early disease progression, even when imaging looked stable
This molecular monitoring could help doctors identify patients who need more aggressive treatment or different approaches.
Why This Matters for Patients
For Surgical Candidates
If you have operable mesothelioma, this trial suggests asking your oncologist about:
- Neoadjuvant immunotherapy before surgery
- ctDNA monitoring to track treatment response
- Adjuvant immunotherapy after surgery
Not all cancer centers offer this approach yet, but the Hopkins data may accelerate adoption.
Current Standard of Care
For comparison, current first-line treatments for unresectable mesothelioma include:
| Treatment | Median Survival | FDA Approved |
|---|---|---|
| Opdivo + Yervoy | 18.1 months | Oct 2020 |
| Chemotherapy (pem/cis) | 12-14 months | 2004 |
| Hopkins trial (surgery + IO) | 28.6 months | Trial only |
The Hopkins approach achieved the longest survival reported in a mesothelioma trial to date, though it applies only to patients whose tumors can be surgically removed.
The Researchers
The trial was led by researchers at Johns Hopkins Kimmel Cancer Center:
- Joshua Reuss, M.D.: Trial designer, now at Georgetown Lombardi
- Results presented at the 2025 World Conference on Lung Cancer (Barcelona)
- Published simultaneously in Nature Medicine
Limitations
Important caveats:
- Small sample size: Phase 2 trials involve fewer patients than Phase 3
- Selected population: Only patients with resectable tumors were eligible
- Single-arm comparison: Results compared to historical data, not a randomized control group
- Access: This approach requires specialized thoracic surgery expertise
What Comes Next
Based on these results, researchers are planning:
- Larger Phase 3 trials to confirm findings
- Studies combining this approach with other treatments
- Expanded ctDNA monitoring protocols
For patients with operable mesothelioma, the Hopkins trial represents a potential new treatment paradigm that dramatically extends survival.
If you have operable mesothelioma, ask your oncologist about neoadjuvant immunotherapy before surgery, ctDNA monitoring to track response, and adjuvant immunotherapy after surgery. Not all cancer centers offer this approach yet, but the Hopkins data may accelerate adoption.
Related Treatment Options
Reader Q&A
Frequently Asked Questions
What is neoadjuvant immunotherapy?
Neoadjuvant therapy is treatment given before surgery. In this trial, patients received nivolumab plus ipilimumab before surgical tumor removal, then continued immunotherapy afterward. This “sandwich” approach aims to shrink tumors before surgery and eliminate remaining cancer cells after.
How does this compare to standard treatment?
The 28.6-month median survival is 59% longer than the typical 18-month survival for people with mesothelioma. It’s also significantly longer than the 18.1 months achieved with Opdivo + Yervoy alone (without surgery) in the FDA approval trial.
What is ctDNA and why does it matter?
Circulating tumor DNA (ctDNA) is cancer DNA that can be detected in blood samples. A “liquid biopsy.” The Hopkins trial found that patients with undetectable ctDNA after treatment had significantly longer survival. This molecular monitoring could help identify patients who need different treatment approaches.
Who is eligible for this treatment approach?
This approach applies only to patients with surgically resectable (operable) mesothelioma. Not all patients qualify. It requires specialized thoracic surgery expertise. Ask your oncologist whether you might be a candidate and if there are trials or treatment centers offering this approach.
What are the end of life symptoms of mesothelioma?
End-of-life symptoms in people with mesothelioma commonly include severe fatigue, shortness of breath, significant weight loss, loss of appetite, chest or abdominal pain, and fluid buildup in the lungs or abdomen. People with pleural mesothelioma often experience coughing up blood, night sweats, and difficulty swallowing, while those with peritoneal mesothelioma may have nausea, diarrhea, and abdominal distention. Additional symptoms near death can involve confusion, delirium, weakness, and changes in breathing patterns, varying by individual and tumor type. Palliative care focuses on symptom management during this stage.
What is the success rate of mesothelioma surgery?
Surgery for pleural mesothelioma, such as pleurectomy/decortication (P/D), is associated with 5-year survival rates of 24% to 67% in early-stage cases, compared to 23% with chemotherapy alone. Median overall survival reaches 40.7 months with surgery versus 23.6 months without. For peritoneal mesothelioma, cytoreductive surgery with HIPEC yields 5-year survival rates of 50% to 80%, with over two-thirds of people with the disease alive at 5 years. These outcomes vary by cancer stage, patient health, and procedure type, outperforming non-surgical treatments in clinical studies. About 27.6% of people with pleural mesothelioma underwent surgery from 2004 to 2020.
Who is the longest survivor of pleural mesothelioma?
Sissy Hoffman is reported as the longest survivor of pleural mesothelioma, diagnosed in 1996 and living 29 years until her death in January 2025 at age 73. She underwent extrapleural pneumonectomy surgery and returned to teaching afterward. Other long-term pleural survivors include Heather von St. James (20 years as of 2025) and Tim Crisler (20 years). Median survival for pleural mesothelioma remains 14-21 months.
Is mesothelioma one of the worst cancers?
Mesothelioma ranks among the deadliest cancers due to its low 5-year survival rate of 7.2-12% across stages, lower than most others except pancreatic cancer at 7.3%. Localized pleural mesothelioma, the most common type affecting over 75-80% of people with the disease, has a 20% 5-year survival rate, dropping to 8% for distant spread. Median life expectancy after diagnosis ranges from 12-21 months with treatment, often shorter without it, reflecting its aggressive nature linked to asbestos exposure. Factors like stage at diagnosis and treatment access influence individual outcomes.