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Neoadjuvant therapy is treatment given before surgery, adjuvant therapy is treatment given after it, and perioperative therapy is both. Neoadjuvant treatment shrinks tumours and shows whether the drug works in the living patient; adjuvant treatment aims to kill microscopic disease left behind.
Neoadjuvant, adjuvant and perioperative therapy mean treatment given before surgery, after surgery, or both; pre-operative and post-operative are the everyday equivalents. Neoadjuvant treatment shrinks tumours, tests drug sensitivity in the living patient through pathologic complete response and can allow surgery to be de-escalated, while adjuvant treatment aims to kill micrometastases. Immunotherapy appears to work better neoadjuvantly, as NADINA and CheckMate 816 suggested, because the primary tumour is still present to supply antigen. The term is anchored to KEYNOTE-522 and referenced by KEYNOTE-671 and SWOG S1801, by the Colorectal, Gastric, Oesophageal, Bladder & urothelial and Head and neck cancer entries, and by the related term Major pathological response (MPR).
The survival benefit first reported in 2023 has held five years after the last dose of adjuvant osimertinib, which answers the worry that a three-year course only delays relapse. Patients with an exon 19 deletion gained most; the L858R estimate crosses one and is less certain. Nothing here changes the recommendation, which already rests on the 2023 analysis, but it tightens the case for testing every resected non-squamous tumour for EGFR mutations.
The adjuvant finding sits uneasily beside BILCAP, on which NHS adjuvant capecitabine rests; in a mostly gallbladder population the benefit is not visible. ACTICCA-1 and ARTEMIDE-Biliary01 are the trials that can settle it.
After bladder removal, a blood test can now tell who needs immunotherapy and who can safely be spared it. This is the model for MRD-guided adjuvant therapy across cancers: treat the blood-positive, watch the blood-negative.
Together with NORPACT-1 this left the neoadjuvant question for resectable disease open: FOLFIRINOX before surgery is not proven superior to alternatives, and the comparison against upfront surgery with adjuvant modified FOLFIRINOX is what PREOPANC-3 and Alliance A021806 are running.
The rationale for OPT-IN and GAIN in one place. Until OPT-IN reports in 2028 the neoadjuvant approach for incidental cancer remains a reasoned choice rather than a proven one.
Adjuvant treatment for lung cancer is now chosen by genotype. A resected ALK-positive tumour is treated with two years of a tablet instead of four cycles of platinum, which is a different life as well as a different outcome.
For the first time a randomised trial suggests that a vaccine tailored to an individual's tumour can reduce relapse when combined with immunotherapy, which is a proof of concept for a field that had failed for decades. Nothing changes for patients yet: the trial was small, the confidence interval crossed one, and the phase 3 trial in melanoma (and parallel trials in lung and other cancers) must confirm it. If it does, personalised mRNA vaccines could become a routine adjunct to checkpoint inhibitors after surgery.
Patients with melanoma that has spread to palpable lymph nodes should now be offered immunotherapy before rather than only after surgery: two cycles of low-dose ipilimumab with nivolumab, then surgery, with the pathology result deciding whether any more treatment is needed. Most patients respond well and are spared a year of adjuvant therapy. Serious side effects are more common than with nivolumab alone, mostly endocrine, and the approach requires close coordination between oncologists, surgeons and pathologists.
Shares A phase III randomised clinical trial of perioperative therapy (neoadjuvant chemotherapy versus chemoradiotherapy) in locally advanced gallbladder cancers (POLCAGB): study protocol, Locally advanced and locoregional disease, Nomogram for predicting the benefit of adjuvant chemoradiotherapy for resected gallbladder cancer, Sauer 2004: chemoradiotherapy before rather than after surgery for rectal cancer (CAO/ARO/AIO-94).
Shares SWOG S1505, PREOPANC-3, Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update, Alliance A021501.
Shares Locally advanced and locoregional disease, Downstaging and conversion therapy, SWOG S1505, Alliance A021501.
Shares MATTERHORN, KEYNOTE-564, CheckMate 238, KEYNOTE-689.
Shares Add a cheap-drug factorial arm to every cooperative-group adjuvant cancer trial, Metastasis prevention as a formal indication with its own trials and regulatory pathway, Bernard Fisher, A short pre-surgery drug window as the default early test of new agents.
Shares NIAGARA, SWOG S1801, MATTERHORN, A short pre-surgery drug window as the default early test of new agents.
Shares JASPAC 01, PREOPANC-3, Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update, Alliance A021806.
Shares Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma, Sauer 2004: chemoradiotherapy before rather than after surgery for rectal cancer (CAO/ARO/AIO-94), Neoadjuvant checkpoint inhibitor → surgery (or no surgery) in dMMR colorectal cancer, Improved survival with preoperative radiotherapy in resectable rectal cancer (Swedish Rectal Cancer Trial).