Neoadjuvant vs. Adjuvant Therapy: When to Start Treatment Before or After Surgery

When you’re facing a cancer diagnosis that requires surgery, one of the most important decisions isn’t about the operation itself-it’s about when to give the drugs. Should treatment come before surgery to shrink the tumor? Or after, to clean up what’s left? This isn’t just a technical question. It’s personal. It affects how long you wait for surgery, how you feel during treatment, and even your chances of staying cancer-free years from now.

What’s the Difference Between Neoadjuvant and Adjuvant Therapy?

It’s simple: neoadjuvant therapy happens before surgery. Adjuvant therapy happens after. Both are systemic treatments-like chemotherapy, immunotherapy, or targeted drugs-that travel through your whole body to kill cancer cells you can’t see.

Neoadjuvant therapy is like testing the waters. You get a few rounds of treatment, then the surgeon removes the tumor. Doctors can look at the removed tissue and see exactly how well the drugs worked. Did the tumor shrink? Did it disappear completely? That answer tells them what’s likely to happen next-and whether they need to change course after surgery.

Adjuvant therapy is more like cleanup. Surgery removes the visible tumor, but there might be tiny clusters of cancer cells hiding elsewhere. Adjuvant treatment aims to wipe those out before they grow back. It’s preventative, not predictive.

Why Neoadjuvant Therapy Is Changing the Game

For years, adjuvant therapy was the standard. But around 2020, things started shifting-especially in lung and breast cancer. The reason? Neoadjuvant therapy gives you real-time feedback.

In a landmark 2022 study called CheckMate 816, patients with stage II-III non-small cell lung cancer got either chemotherapy alone or chemotherapy plus the immunotherapy drug nivolumab before surgery. The results were striking: 24% of patients who got the combo had a pathologic complete response (pCR)-meaning no living cancer cells were found in the tumor after treatment. Only 2.2% of those who got chemo alone had that result.

That’s not just a number. For patients, seeing that their tumor responded so well before surgery is a huge psychological win. One patient on a cancer forum wrote: “My oncologist said 90% of the tumor was dead. That gave me hope I didn’t have before.”

Neoadjuvant therapy also helps surgeons. If a tumor shrinks enough, they might be able to do a less invasive operation-like saving a lung lobe instead of removing the whole lung. It also tackles micrometastases early, before surgery can spread cells around.

When Adjuvant Therapy Still Makes Sense

That doesn’t mean adjuvant therapy is outdated. For many patients, especially those with smaller tumors or slower-growing cancers, it’s still the best path.

Some people don’t want to delay surgery. They’re anxious to get the tumor out as soon as possible. Others have tumors that don’t respond well to drugs upfront. In those cases, removing the tumor first and then treating the leftovers is safer and more predictable.

For breast cancer, studies show that patients with triple-negative or HER2-positive subtypes benefit most from neoadjuvant chemo. But for hormone-receptor-positive cancers, especially in older patients, doctors often still start with surgery, then add hormone therapy afterward. The difference in survival between the two approaches is small-but the side effects aren’t.

The Big Shift: Neoadjuvant-Only Is Gaining Ground

Here’s where things get really interesting. For a long time, the plan was: neoadjuvant therapy, then surgery, then more therapy (adjuvant). But new data is challenging that.

A 2024 meta-analysis of over 3,200 patients found that adding adjuvant immunotherapy after neoadjuvant treatment didn’t improve survival-but it did increase serious side effects. Patients on the full combo had nearly 30% chance of grade 3 or higher side effects like lung inflammation, liver damage, or severe fatigue. Those who stopped after neoadjuvant therapy? Around 18%.

Dr. Mark Awad from Dana-Farber put it bluntly in an ASCO talk: “The neoadjuvant-only approach may be the optimal strategy for early-stage lung cancer.”

That’s not a blanket rule. It depends on your tumor’s biology. If your tumor had a strong response to neoadjuvant treatment-like a pCR-you might not need more. But if the tumor barely changed? That’s a red flag. You might still need adjuvant therapy to reduce the risk of relapse.

How Doctors Decide: Biomarkers and Response

This isn’t guesswork. Doctors use specific tools to guide decisions.

• PD-L1 expression: In lung cancer, if your tumor has PD-L1 levels of 1% or higher, you’re more likely to respond to immunotherapy. That makes neoadjuvant combo therapy a strong option.
• Pathologic complete response (pCR): After surgery, the pathologist checks the tumor tissue. No viable cancer cells? That’s a pCR. Patients with pCR have significantly better long-term survival-sometimes 70-80% at five years.
• Tumor subtype: Triple-negative breast cancer? Neoadjuvant chemo is standard. HER2-positive? Neoadjuvant chemo plus targeted drugs like trastuzumab. Hormone-positive? Often surgery first, then endocrine therapy.

Doctors also use imaging-CT scans, PET scans-to track tumor size before and after treatment. But scans can lie. That’s why the final pathology report after surgery is the gold standard.

What About Side Effects and Timing?

Neoadjuvant therapy usually means 3 to 4 cycles of treatment over 9 to 12 weeks before surgery. That’s a long time to wait, especially if you’re in pain or anxious. About 10-15% of patients experience delays because of side effects like low blood counts, nerve damage, or infections.

Adjuvant therapy starts after you’ve healed from surgery-usually 4 to 6 weeks later-and continues for 4 to 6 months. It’s less disruptive to your recovery, but you’re still dealing with fatigue, nausea, or immune-related issues.

One trade-off: Neoadjuvant therapy means you’re getting treatment while your body is still strong. Adjuvant therapy comes when you’re still recovering from surgery. For some, that’s harder.

Who Gets Which Treatment? Guidelines in 2025

The National Comprehensive Cancer Network (NCCN) updated its guidelines in early 2024. Here’s what they recommend:

• Non-small cell lung cancer (NSCLC): Neoadjuvant chemoimmunotherapy for stage IB (tumor ≥4 cm) to IIIA. Surgery should happen 3 to 6 weeks after the last dose.
• Triple-negative breast cancer: Neoadjuvant chemo is standard for stage II or III. If pCR is achieved, no additional chemo is needed.
• HER2-positive breast cancer: Neoadjuvant chemo plus trastuzumab and pertuzumab. Surgery after 4-6 cycles.
• Hormone-receptor-positive breast cancer: Usually surgery first, then hormone therapy for 5-10 years. Neoadjuvant is only considered if the tumor is large or growing fast.

But guidelines aren’t law. They’re starting points. Your oncologist will consider your age, overall health, tumor genetics, and personal preferences.

The Real-World Gap: Access and Expertise

Here’s the catch: Not every hospital can do this well.

Academic centers have multidisciplinary teams-surgeons, oncologists, radiologists, pathologists-all talking daily. Community hospitals? Only 58% have formal neoadjuvant pathways, according to a 2023 study. That means patients in smaller towns might not even be offered neoadjuvant options.

Also, interpreting response isn’t easy. You need pathologists trained in grading tumor response using systems like Miller-Payne for breast cancer or the American College of Pathologists system for lung. Not every lab does this consistently.

If you’re considering neoadjuvant therapy, ask: “Does your team have experience with this? Do they review cases together? Can they explain what a pCR means for me?”

What’s Next? The Future of Sequencing

Doctors aren’t stopping here. The next big thing is using circulating tumor DNA (ctDNA)-tiny pieces of cancer DNA floating in your blood-to guide treatment.

After surgery, if ctDNA is still detectable, it means cancer cells are still hiding. That’s a sign you need more treatment. If it’s gone? You might be able to avoid adjuvant therapy entirely.

Trials like NeoADAURA (for EGFR-mutant lung cancer) and KEYNOTE-867 are testing exactly this. Early results suggest ctDNA could become the new way to decide who needs more drugs-and who doesn’t.

By 2030, experts predict that 70% of early-stage lung cancer patients will get neoadjuvant therapy tailored to their tumor’s genetic profile. Survival rates could jump from 65% to over 75%.

That’s not science fiction. It’s happening now.

What Should You Do?

If you’re facing surgery for cancer, ask these questions:

1. Is neoadjuvant therapy an option for my type and stage of cancer?
2. What’s my chance of a pathologic complete response?
3. Will we test for PD-L1 or other biomarkers?
4. What happens if the tumor doesn’t shrink?
5. Can we monitor ctDNA after surgery?
6. Do you have a team that handles neoadjuvant cases regularly?

There’s no one-size-fits-all answer. But knowing the difference between neoadjuvant and adjuvant therapy gives you power. It lets you ask better questions, make smarter choices, and take part in your own care.

The goal isn’t just to survive. It’s to survive with fewer side effects, less fear, and more confidence that you got the right treatment at the right time.