Neoadjuvant vs Adjuvant Therapy: Treatment Before and After Surgery

Neoadjuvant therapy is drug treatment given before surgery; adjuvant therapy is given after it. The drugs can be exactly the same — the difference is the goal. Before surgery, we shrink the tumor and see how it responds to treatment. After surgery, we destroy cells that may have stayed in the body and can’t be seen on any scan.

Below I’ll explain why “chemo first, then surgery” doesn’t mean things are bad, and what pCR is — a term patients often come across online.

How neoadjuvant treatment differs from adjuvant treatment

Adjuvant therapy (from the Latin for “helping”) is given after the tumor has been removed. In the words of the American Cancer Society, its goal is to kill cancer cells that may have been left behind after surgery. The surgeon removes everything that can be seen, but individual cells may already have entered the blood or lymph. Adjuvant treatment lowers the risk that a recurrence will grow from them over time (more on why cancer can come back years later).

Neoadjuvant therapy is given before surgery. It has several goals:

• to shrink the tumor so the operation can be less extensive;
• to make a tumor that is hard to remove straight away operable;
• to see whether the tumor is sensitive to the chosen drugs;
• to gain information that affects treatment after surgery.

In breast cancer there’s a telling fact: according to the American Cancer Society, chemotherapy works equally well before and after surgery. So by moving it “forward”, we lose nothing and gain extra information.

Adjuvant treatment isn’t necessarily chemotherapy. Depending on the type of tumor, hormone therapy, targeted therapy or immunotherapy may be given after surgery, sometimes several types one after another. And in some cases no additional treatment is needed after surgery at all: if the risk of recurrence is low, the benefit of treatment may not outweigh its side effects. This decision is based on the final histology and stage, so it often can’t be made definitively before surgery.

Why chemo is given before surgery if the tumor can be removed

Patients often ask me: “I was told chemo comes first — does that mean I can’t have surgery?” No. This is one of the most common and most frightening misunderstandings.

Neoadjuvant treatment is given to exactly the people who are planned for surgery. In breast cancer it’s often used when the tumor is large, many lymph nodes are involved, or the cancer is inflammatory. In rectal cancer, total neoadjuvant therapy (TNT) — where both chemotherapy and radiation therapy are given before surgery — has become the preferred approach in the NCCN guidelines for most locally advanced tumors. The order of the stages can vary, and the approach itself is still being debated: the American Cancer Society notes that not all doctors agree with it.

The decision “drugs first, then the surgeon” is made by a multidisciplinary tumor board — the surgeon, medical oncologist and radiation oncologist together. If you feel the reasoning in your case hasn’t been explained, ask your doctor to talk it through: what the treatment before surgery is meant to achieve and what will count as success.

What pCR — pathologic complete response — means

pCR (pathologic complete response) is when, after neoadjuvant treatment and surgery, the pathologist finds no living invasive tumor cells in the removed tissue.

In breast cancer, the largest pooled analysis, CTNeoBC (12 international trials, almost 12,000 patients), defined pCR as no invasive tumor in either the breast or the lymph nodes (written as ypT0/is ypN0). Residual ductal carcinoma in situ is allowed. This definition was the one most closely linked to prognosis — more closely than the tumor disappearing from the breast alone.

I explained how to read these notations in the report in my article on the pathology report. The prefix “y” means the stage is assessed after treatment given before surgery.

Why pCR matters — and where its importance shouldn’t be overstated

Breast cancer patients who achieve pCR have, on average, better survival. The American Cancer Society states directly that in triple-negative and HER2-positive cancer, complete disappearance of the tumor before surgery is linked to better survival. In the CTNeoBC analysis the link was strongest precisely in the aggressive subtypes.

There are two caveats I always talk through.

First: pCR is a sign of a favorable prognosis for an individual person, but not a guarantee. The authors of that same analysis could not confirm that a higher pCR rate in a trial automatically means better survival. So pCR isn’t a promise that “it won’t come back”, but one important marker.

Second: not achieving pCR isn’t a death sentence, and it doesn’t mean “the treatment didn’t work”. The tumor may have shrunk considerably. What’s more, if tumor remains, doctors may recommend additional treatment after surgery to lower the risk of recurrence. This is one of the advantages of the neoadjuvant approach: we learn who needs their treatment stepped up.

In breast cancer, the significance of pCR depends on the tumor subtype: it’s most pronounced in triple-negative and HER2-positive cancer. That’s why a doctor reads the same surgical result differently depending on your immunohistochemistry profile.

Rectal cancer: when surgery may not be done

Rectal cancer is a special case. Sometimes after chemoradiation the tumor can no longer be detected on examination, endoscopy and MRI — this is called a clinical complete response. In such cases some centers discuss a “watch-and-wait” approach: surgery is postponed and very close surveillance is carried out.

According to NCCN, this is an option only for carefully selected patients who agree to an intensive surveillance program. Surveillance includes digital rectal examination, endoscopy and pelvic MRI using a special protocol. NCCN notes that the benefits and risks of this approach compared with surgery are not yet fully understood, and the decision is made together with your doctor.

I wouldn’t see this as a “way to avoid surgery”. It’s a separate strategy with its own conditions: the center’s experience, disciplined surveillance and readiness for surgery if the tumor comes back.

How response to neoadjuvant treatment is assessed

Response is assessed at two levels.

During treatment — clinically and with tests: examination, palpation, ultrasound, MRI, and in rectal cancer, endoscopy and pelvic MRI. The aim is to make sure the tumor isn’t growing during therapy and, if needed, to change the plan in time.

After surgery — pathologically. Only examining the removed tissue under a microscope shows whether any living tumor cells remain, how many, and whether the lymph nodes are involved. Scans may show “nothing visible” while a small residue is found under the microscope — and the other way round: scar tissue with no living cells can remain visible on MRI.

Questions to ask your doctor

• Why is treatment starting before surgery (or after) in my case? What is it meant to achieve?
• How and when will response to treatment be assessed: which tests, after which cycle?
• What happens if the tumor doesn’t shrink or starts to grow?
• What would pCR mean for me — and how will the plan change if there’s no complete response?
• Will I need treatment after surgery, and what will that depend on?
• (In rectal cancer) Is a watch-and-wait approach being considered in my case, and what are its conditions?

If you’ve received a treatment plan and want to go through it calmly, I’ll review your documents and plan in a consultation and suggest which questions to discuss with the tumor board.

Sources

1. Chemotherapy for Breast Cancer — American Cancer Society
2. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis — Cortazar P. et al., Lancet, 2014
3. NCCN Guidelines for Patients: Rectal Cancer — NCCN, 2022
4. Treatment of Rectal Cancer, by Stage — American Cancer Society