{"id":"surgery-roadmap","name":"Surgery roadmap: radical operations → less surgery → no surgery when a drug has done the work","route":"/roadmaps/surgery-roadmap/","eras":[{"era":"1890s-1990s","title":"From radical to conservative, one trial at a time","description":"Halsted's radical mastectomy set the template that more tissue meant more cure. Randomised trials dismantled it: breast conservation with radiation matched mastectomy, and sentinel lymph node biopsy replaced clearing every node in breast cancer and melanoma. The lesson that survives is that the extent of surgery must be tested, not inferred from anatomy.","status":"historic","refs":[{"id":"sentinel-node","kind":"technology","name":"Sentinel lymph node biopsy","route":"/technologies/sentinel-node/","status":"standard-of-care","tldr":"Removing just the first lymph node a tumour drains to, instead of all of them, to check for spread."},{"id":"mslt-ii","kind":"trial","name":"MSLT-II","route":"/trials/mslt-ii/","status":"positive","tldr":"Showed that removing all the remaining lymph nodes after a positive sentinel node does not help patients live longer, ending a routine operation."},{"id":"fires-sentor","kind":"trial","name":"FIRES & SENTOR (sentinel node mapping)","route":"/trials/fires-sentor/","status":"positive","tldr":"Mapping and removing only the first draining lymph nodes finds spread as reliably as removing all of them, with far less lymphoedema."},{"id":"limb-salvage-surgery","kind":"technology","name":"Limb-salvage surgery and endoprosthetic reconstruction","route":"/technologies/limb-salvage-surgery/","status":"standard-of-care","tldr":"Removing a bone or soft-tissue sarcoma while keeping the arm or leg, rebuilding with metal implants, bone grafts or growing prostheses in children."}],"trials":[{"id":"mslt-ii","name":"MSLT-II","route":"/trials/mslt-ii/","outcomes":[{"endpoint":"Melanoma-specific survival at 3 years","primary":true,"unit":"%","arms":[{"name":"Completion dissection","value":86},{"name":"Observation","value":86}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1613210"}],"setting":"Sentinel-node-positive melanoma: immediate completion lymph node dissection vs ultrasound surveillance","enrolled":1939,"enrolledBasis":"registry"},{"id":"fires-sentor","name":"FIRES & SENTOR (sentinel node mapping)","route":"/trials/fires-sentor/","outcomes":[{"endpoint":"FIRES: sensitivity of sentinel-node mapping for nodal metastasis","primary":true,"unit":"%","arms":[{"name":"ICG sentinel-node mapping vs complete lymphadenectomy","n":340,"value":97.2,"note":"95% CI 85.0-100; 385 enrolled, 340 analysed; negative predictive value 99.6% (95% CI 97.9-100)"}],"source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30068-2/fulltext"},{"endpoint":"SENTOR: sensitivity of the sentinel-node algorithm in intermediate/high-grade endometrial cancer","primary":true,"unit":"%","arms":[{"name":"ICG sentinel-node biopsy vs lymphadenectomy","n":156,"value":96,"note":"95% CI 81-100; negative predictive value 99% (95% CI 96-100); false-negative rate 4%"}],"source":"https://doi.org/10.1001/jamasurg.2020.5060"}],"setting":"Endometrial cancer staging: indocyanine-green sentinel lymph node mapping compared against full lymphadenectomy","enrolledBasis":"registry"}],"papers":[]},{"era":"2000s-2018","title":"Smaller incisions, robots and a warning","description":"Laparoscopic and robotic surgery cut blood loss and recovery time across prostate, kidney, colon and gynaecological cancers, and transoral robotic surgery let throat tumours be removed without splitting the jaw. LACC (2018) showed that keyhole surgery for cervical cancer had more recurrences than open surgery, a reminder that a smaller scar is not automatically the same operation. Endoscopic resection now removes the earliest oesophageal and stomach cancers from the inside.","status":"historic","refs":[{"id":"robotic-surgery","kind":"technology","name":"Robotic & minimally invasive surgery","route":"/technologies/robotic-surgery/","status":"standard-of-care","tldr":"Surgeons operate through small incisions using robotic arms with tremor-free precision and 3D vision."},{"id":"tors","kind":"technology","name":"Transoral robotic surgery (TORS)","route":"/technologies/tors/","status":"established","tldr":"Transoral robotic surgery removes early (T1 to T2) throat tumours through the mouth with a robot and 3D endoscope, avoiding splitting the jaw or a tracheostomy. In HPV-positive oropharyngeal cancer the pathology then guides how much radiation to add, but randomised trials found it no better than radiation for swallowing, and surgeon volume matters."},{"id":"endoscopic-resection","kind":"technology","name":"Endoscopic resection (EMR / ESD)","route":"/technologies/endoscopic-resection/","status":"standard-of-care","tldr":"Endoscopic resection lifts an early cancer of the oesophagus or stomach with an injection and cuts it out from inside with a snare or electrosurgical knife, keeping the organ intact. It cures cancers confined to the mucosa (T1a) and gives a definitive depth reading; deeper invasion or lymph node spread still needs surgery."},{"id":"lacc","kind":"trial","name":"LACC (Laparoscopic Approach to Cervical Cancer)","route":"/trials/lacc/","status":"negative","tldr":"Keyhole surgery, assumed equivalent, turned out to be worse: more recurrences and more deaths than open surgery, reversing practice overnight."},{"id":"robotic-bronchoscopy","kind":"technology","name":"Robotic and navigational bronchoscopy","route":"/technologies/robotic-bronchoscopy/","status":"established","tldr":"A robot-guided flexible scope that reaches small lung nodules through the airways to biopsy them without a needle through the chest wall."},{"id":"elective-neck-dissection-tmh","kind":"trial","name":"Elective vs therapeutic neck dissection in node-negative oral cancer (Tata Memorial)","route":"/trials/elective-neck-dissection-tmh/","status":"positive","tldr":"A Tata Memorial trial ended a 50-year debate by showing that removing the neck lymph nodes at the first operation for early mouth cancer raises three-year survival from about two-thirds to four-fifths."}],"trials":[{"id":"lacc","name":"LACC (Laparoscopic Approach to Cervical Cancer)","route":"/trials/lacc/","outcomes":[{"endpoint":"Disease-free survival at 4.5 years","primary":true,"unit":"%","arms":[{"name":"Minimally invasive","n":319,"value":86},{"name":"Open surgery","n":312,"value":96.5}],"hr":3.74,"ci":[1.63,8.58],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1806395"},{"endpoint":"Overall survival at 3 years","unit":"%","arms":[{"name":"Minimally invasive","value":93.8},{"name":"Open surgery","value":99}],"hr":6,"ci":[1.77,20.3],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1806395"}],"setting":"Early-stage cervical cancer (IA1 with LVSI to IB1): minimally invasive vs open radical hysterectomy","enrolled":636,"enrolledBasis":"registry"},{"id":"elective-neck-dissection-tmh","name":"Elective vs therapeutic neck dissection in node-negative oral cancer (Tata Memorial)","route":"/trials/elective-neck-dissection-tmh/","outcomes":[{"endpoint":"3-year overall survival","primary":true,"unit":"%","arms":[{"name":"Elective neck dissection","n":245,"value":80},{"name":"Therapeutic neck dissection","n":255,"value":67.5}],"hr":0.64,"ci":[0.45,0.92],"p":"0.01","source":"https://doi.org/10.1056/NEJMoa1506007"}],"setting":"Early-stage (T1-T2) node-negative oral squamous cell cancer: elective neck dissection at primary surgery vs watchful waiting with therapeutic dissection at nodal relapse","enrolled":596,"enrolledNote":"ClinicalTrials.gov lists an estimated 710 participants and the record's status is unknown, meaning the sponsor has not verified it recently; the NEJM 2015 paper reports 596 patients enrolled between 2004 and 2014, with the first 500 analysed.","enrolledBasis":"registered"}],"papers":[]},{"era":"2018-2026","title":"The drug arrives before the surgeon","description":"Giving immunotherapy or targeted therapy before the operation, when the immune system can still see the whole tumour, improved event-free and overall survival in lung cancer (CheckMate 816, KEYNOTE-671), melanoma (SWOG S1801, NADINA), bladder cancer (NIAGARA), stomach cancer (MATTERHORN) and triple-negative breast cancer (KEYNOTE-522). The pathological response at surgery now tells the team how much treatment is needed afterwards, and pre-surgery windows have become the fastest way to test new combinations.","status":"current","refs":[{"id":"checkmate-816","kind":"trial","name":"CheckMate 816","route":"/trials/checkmate-816/","status":"positive","tldr":"CheckMate 816 was the first trial to show that immunotherapy before lung cancer surgery improves survival."},{"id":"keynote-671","kind":"trial","name":"KEYNOTE-671","route":"/trials/keynote-671/","status":"positive","tldr":"Showed that immunotherapy given both before and after lung cancer surgery lengthens survival."},{"id":"swog-s1801","kind":"trial","name":"SWOG S1801","route":"/trials/swog-s1801/","status":"positive","tldr":"Simply moving three doses of the same drug to before surgery improved outcomes, a result that changed how the field thinks about timing."},{"id":"nadina","kind":"trial","name":"NADINA","route":"/trials/nadina/","status":"positive","tldr":"Giving the immunotherapy doublet before surgery, instead of nivolumab after, cut the risk of recurrence by about two thirds and let most patients skip further treatment."},{"id":"niagara","kind":"trial","name":"NIAGARA","route":"/trials/niagara/","status":"positive","tldr":"The first immunotherapy shown to improve survival when given around bladder-removal surgery."},{"id":"matterhorn","kind":"trial","name":"MATTERHORN","route":"/trials/matterhorn/","status":"positive","tldr":"Adding immunotherapy before and after surgery cut deaths in early stomach cancer; nearly seven in ten patients were alive at three years."},{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/","status":"positive","tldr":"The trial that added immunotherapy to pre-surgery chemotherapy for triple-negative breast cancer and, uniquely, improved survival."},{"id":"destiny-breast11","kind":"trial","name":"DESTINY-Breast11","route":"/trials/destiny-breast11/","status":"positive","tldr":"DESTINY-Breast11 brought Enhertu into pre-surgery treatment of HER2-positive breast cancer, replacing anthracyclines."},{"id":"preopanc","kind":"trial","name":"PREOPANC-1","route":"/trials/preopanc/","status":"mixed","tldr":"The Dutch trial testing whether treating before surgery beats operating first. Chemoradiation first fell short at the primary analysis but won at five years, with one in five patients alive against one in fifteen."},{"id":"idea-bio2-neoadjuvant-biomarker-engine","kind":"idea","name":"Use pre-surgery immunotherapy windows as the field's biomarker engine","route":"/ideas/idea-bio2-neoadjuvant-biomarker-engine/","tldr":"Giving immunotherapy for a few weeks before surgery produces a tumour sample that shows exactly what the drug did. That is the fastest way to learn who responds."},{"id":"idea-tr1-window-of-opportunity-default","kind":"idea","name":"A short pre-surgery drug window as the default early test of new agents","route":"/ideas/idea-tr1-window-of-opportunity-default/","tldr":"Between diagnosis and surgery there are usually a few weeks. Giving a new drug in that window and comparing the tumour before and after surgery shows whether it hits its target in real people, quickly and cheaply."}],"trials":[{"id":"checkmate-816","name":"CheckMate 816","route":"/trials/checkmate-816/","outcomes":[{"endpoint":"Pathologic complete response","primary":true,"unit":"%","arms":[{"name":"Nivolumab + chemotherapy","n":179,"value":24},{"name":"Chemotherapy","n":179,"value":2.2}],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2202170"},{"endpoint":"Event-free survival","primary":true,"unit":"months","arms":[{"name":"Nivolumab + chemotherapy","value":31.6},{"name":"Chemotherapy","value":20.8}],"hr":0.63,"ci":[0.43,0.91],"p":"0.005","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2202170"},{"endpoint":"Overall survival at 5 years","unit":"%","arms":[{"name":"Nivolumab + chemotherapy","value":65},{"name":"Chemotherapy","value":55}],"hr":0.72,"ci":[0.52,0.99],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2502256"}],"setting":"Resectable stage IB-IIIA NSCLC: neoadjuvant nivolumab + platinum chemotherapy (3 cycles) vs chemotherapy","enrolled":358,"enrolledNote":"ClinicalTrials.gov lists 505 participants (actual) across all arms, including nivolumab plus ipilimumab; the NEJM 2022 primary analysis compared 179 patients randomised to nivolumab plus chemotherapy with 179 randomised to chemotherapy.","enrolledBasis":"randomised"},{"id":"keynote-671","name":"KEYNOTE-671","route":"/trials/keynote-671/","outcomes":[{"endpoint":"Event-free survival","primary":true,"unit":"months","arms":[{"name":"Pembrolizumab + chemotherapy → pembrolizumab","n":397,"value":47.2},{"name":"Placebo + chemotherapy → placebo","n":400,"value":18.3}],"hr":0.59,"ci":[0.48,0.72],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2302983"},{"endpoint":"Overall survival at 36 months","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab arm","value":71.3},{"name":"Placebo arm","value":64}],"hr":0.72,"ci":[0.56,0.93],"p":"0.005","source":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02241-2/fulltext"}],"setting":"Resectable stage II-IIIB NSCLC: neoadjuvant pembrolizumab + chemotherapy then adjuvant pembrolizumab vs placebo","enrolled":797,"enrolledBasis":"registry"},{"id":"swog-s1801","name":"SWOG S1801","route":"/trials/swog-s1801/","outcomes":[{"endpoint":"Event-free survival at 2 years","primary":true,"unit":"%","arms":[{"name":"Neoadjuvant + adjuvant pembrolizumab","value":72},{"name":"Adjuvant pembrolizumab","value":49}],"hr":0.58,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2211437"}],"setting":"Resectable stage IIIB-IV melanoma: three doses of pembrolizumab before surgery then 15 after, vs 18 doses after surgery","enrolled":313,"enrolledBasis":"registry"},{"id":"nadina","name":"NADINA","route":"/trials/nadina/","outcomes":[{"endpoint":"Event-free survival at 12 months","primary":true,"unit":"%","arms":[{"name":"Neoadjuvant ipilimumab + nivolumab","value":83.7},{"name":"Adjuvant nivolumab","value":57.2}],"hr":0.32,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2402604"}],"setting":"Resectable macroscopic stage III melanoma: two cycles neoadjuvant ipilimumab + nivolumab then surgery (adjuvant only if incomplete response) vs surgery then 12 cycles adjuvant nivolumab","enrolled":423,"enrolledBasis":"registry"},{"id":"niagara","name":"NIAGARA","route":"/trials/niagara/","outcomes":[{"endpoint":"Event-free survival","primary":true,"unit":"months","arms":[{"name":"Durvalumab + chemo, perioperative","n":533,"note":"median not reached"},{"name":"Chemo + cystectomy","n":530,"value":46.1}],"hr":0.68,"ci":[0.56,0.82],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2408154"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Durvalumab arm","note":"not reached"},{"name":"Control","note":"not reached"}],"hr":0.75,"ci":[0.59,0.93],"p":"0.01","source":"https://doi.org/10.1056/NEJMoa2408154"}],"setting":"Cisplatin-eligible muscle-invasive bladder cancer: neoadjuvant durvalumab + gemcitabine-cisplatin, cystectomy, adjuvant durvalumab vs neoadjuvant chemotherapy and cystectomy","enrolled":1063,"enrolledBasis":"registry"},{"id":"matterhorn","name":"MATTERHORN","route":"/trials/matterhorn/","outcomes":[{"endpoint":"Event-free survival","primary":true,"arms":[{"name":"FLOT + durvalumab","n":474},{"name":"FLOT + placebo","n":474}],"hr":0.71,"source":"https://clinicaltrials.gov/study/NCT04592913"},{"endpoint":"Overall survival","arms":[{"name":"FLOT + durvalumab","n":474},{"name":"FLOT + placebo","n":474}],"hr":0.78,"ci":[0.63,0.96],"p":"0.021","source":"https://ascopost.com/issues/december-10-2025-supplement-conference-highlights-esmo-2025/final-overall-survival-confirms-benefit-of-durvalumab-plus-flot-in-resectable-gastric-and-gastroesophageal-junction-adenocarcinomas/"},{"endpoint":"Pathologic complete response","unit":"percent","arms":[{"name":"FLOT + durvalumab","value":19.2},{"name":"FLOT + placebo","value":7.2}],"source":"https://www.cancernetwork.com/view/behind-the-matterhorn-trial-of-durvalumab-flot-in-gastric-gej-cancer"}],"setting":"Resectable stage II-IVA gastric/GEJ adenocarcinoma: perioperative FLOT + durvalumab vs FLOT + placebo","enrolled":957,"enrolledBasis":"registry"},{"id":"keynote-522","name":"KEYNOTE-522","route":"/trials/keynote-522/","outcomes":[{"endpoint":"Pathologic complete response (ypT0/Tis ypN0)","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","n":401,"value":64.8},{"name":"Placebo + chemotherapy","n":201,"value":51.2}],"p":"0.00055","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1910549"},{"endpoint":"Event-free survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","n":784,"value":81.2},{"name":"Placebo + chemotherapy","n":390,"value":72.2}],"hr":0.65,"ci":[0.51,0.83],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2409932"},{"endpoint":"Overall survival at 5 years","unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","value":86.6},{"name":"Placebo + chemotherapy","value":81.7}],"hr":0.66,"ci":[0.5,0.87],"p":"0.002","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2409932"},{"endpoint":"Event-free survival at 7 years","unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","value":78.3},{"name":"Placebo + chemotherapy","value":69.8}],"source":"https://www.lbbc.org/news/pivotal-progress-in-tnbc-asco-2026"},{"endpoint":"Overall survival at 7 years","unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","value":85.1},{"name":"Placebo + chemotherapy","value":77.2}],"source":"https://www.lbbc.org/news/pivotal-progress-in-tnbc-asco-2026"}],"setting":"Early-stage (II-III) TNBC: pembrolizumab + chemotherapy before surgery, pembrolizumab after","enrolled":1174,"enrolledBasis":"registry"},{"id":"destiny-breast11","name":"DESTINY-Breast11","route":"/trials/destiny-breast11/","outcomes":[{"endpoint":"Pathologic complete response (ypT0/Tis ypN0)","primary":true,"unit":"%","arms":[{"name":"T-DXd → THP","n":321,"value":67.3},{"name":"ddAC → THP","n":320,"value":56.3}],"p":"0.003","source":"https://web.archive.org/web/20231201043719/https://www.esmo.org/newsroom/press-releases"},{"endpoint":"Event-free survival","unit":"months","arms":[{"name":"T-DXd → THP","note":"Immature; the T-DXd monotherapy arm was stopped early for lower efficacy."},{"name":"ddAC → THP"}]}],"setting":"Neoadjuvant high-risk HER2+ early breast cancer: T-DXd followed by THP vs ddAC-THP","enrolled":927,"enrolledBasis":"registry"},{"id":"preopanc","name":"PREOPANC-1","route":"/trials/preopanc/","outcomes":[{"endpoint":"Overall survival (long-term)","primary":true,"unit":"%","arms":[{"name":"Neoadjuvant chemoradiotherapy, 5-year OS","n":119,"value":20.5},{"name":"Upfront surgery, 5-year OS","n":127,"value":6.5}],"hr":0.73,"ci":[0.56,0.96],"p":"0.025","source":"https://ascopubs.org/doi/10.1200/JCO.21.02233"},{"endpoint":"Overall survival (primary analysis, intention to treat)","unit":"months","arms":[{"name":"Neoadjuvant gemcitabine chemoradiotherapy, surgery, adjuvant gemcitabine","n":119,"value":16},{"name":"Upfront surgery, adjuvant gemcitabine","n":127,"value":14.3}],"hr":0.78,"ci":[0.58,1.05],"p":"0.096","source":"https://doi.org/10.1200/JCO.19.02274"},{"endpoint":"R0 resection rate among resected patients","unit":"%","arms":[{"name":"Neoadjuvant chemoradiotherapy","n":72,"value":71,"note":"51 of 72"},{"name":"Upfront surgery","n":92,"value":40,"note":"37 of 92"}],"p":"<0.001","source":"https://doi.org/10.1200/JCO.19.02274"}],"setting":"Resectable and borderline-resectable PDAC at 16 Dutch centres: neoadjuvant gemcitabine-based chemoradiation (36 Gy in 15 fractions), surgery and adjuvant gemcitabine vs upfront surgery and adjuvant gemcitabine","enrolled":246,"enrolledBasis":"registry"}],"papers":[]},{"era":"2022-2028","title":"Organ preservation and no surgery at all","description":"In mismatch-repair-deficient bowel cancer, a few weeks of immunotherapy clears most tumours completely (NICHE-2), and AZUR-1 is the registrational test of skipping surgery, radiation and chemotherapy entirely. SANO showed that watching closely after chemoradiation for oesophageal cancer, operating only if the tumour returns, is safe for the third of patients whose tumour has vanished. ESTIMABL2 let most low-risk thyroid cancers skip radioactive iodine; small kidney tumours and papillary microcarcinomas are increasingly watched rather than removed. MARS 2 showed that a major mesothelioma operation did not help, and practice changed.","status":"current","refs":[{"id":"niche-2","kind":"trial","name":"NICHE-2","route":"/trials/niche-2/","status":"positive","tldr":"In NICHE-2, four weeks of immunotherapy before surgery wiped out most mismatch-repair-deficient colon cancers, and nobody had relapsed three years later."},{"id":"azur-1","kind":"trial","name":"AZUR-1","route":"/trials/azur-1/","status":"positive","tldr":"AZUR-1 is the registrational trial of the 'no surgery, no radiation, no chemo' approach for mismatch-repair-deficient rectal cancer, built on the MSK study where every patient had a complete response."},{"id":"sano","kind":"trial","name":"SANO","route":"/trials/sano/","status":"positive","tldr":"For the third of patients whose tumour vanishes after chemoradiation, watching closely and operating only if it comes back gave the same survival as immediate surgery."},{"id":"estimabl2","kind":"trial","name":"ESTIMABL2","route":"/trials/estimabl2/","status":"positive","tldr":"Proved that most people with small, low-risk thyroid cancers can skip radioactive iodine after surgery without any increase in recurrence."},{"id":"mars-2","kind":"trial","name":"MARS 2","route":"/trials/mars-2/","status":"negative","tldr":"MARS 2 is the trial that overturned decades of surgical practice: removing the lining of the lung did not help patients live longer and left them worse off."},{"id":"partial-nephrectomy-active-surveillance","kind":"technology","name":"Partial nephrectomy, ablation & active surveillance of small renal masses","route":"/technologies/partial-nephrectomy-active-surveillance/","status":"standard-of-care","tldr":"Most small kidney tumours found on scans grow slowly. Options range from watching them, to freezing or heating them, to removing just the tumour and keeping the kidney."},{"id":"active-surveillance-thyroid","kind":"technology","name":"Active surveillance of papillary microcarcinoma","route":"/technologies/active-surveillance-thyroid/","status":"established","tldr":"Active surveillance watches papillary thyroid cancers of 1 cm or less with ultrasound every 6 to 12 months instead of operating, because about 90% stay stable over a decade and delayed surgery works as well when needed. It is not suitable for tumours next to the windpipe or the voice nerve, and uptake outside Japan and Korea is still low."},{"id":"idea-prev-small-renal-mass-surveillance","kind":"idea","name":"Watch small kidney tumours rather than remove them, with a national registry","route":"/ideas/idea-prev-small-renal-mass-surveillance/","tldr":"Most kidney tumours under 3 cm found by chance grow under 0.3 cm a year, rarely spread, and a fifth are benign. Surveillance with a biopsy for grade as the default in patients over 65, with a national registry and set triggers for surgery, could spare most of these operations."}],"trials":[{"id":"niche-2","name":"NICHE-2","route":"/trials/niche-2/","outcomes":[{"endpoint":"Pathologic complete response","primary":true,"unit":"percent","arms":[{"name":"Neoadjuvant nivolumab + ipilimumab","n":111,"value":68}],"source":"https://www.nejm.org/doi/abs/10.1056/NEJMoa2400634"},{"endpoint":"3-year disease-free survival","unit":"percent","arms":[{"name":"Neoadjuvant nivolumab + ipilimumab","n":111,"value":100}],"source":"https://www.annalsofoncology.org/article/S0923-7534(24)03843-2/fulltext"}],"setting":"Locally advanced (mostly stage III) dMMR colon cancer: 4 weeks of neoadjuvant nivolumab + one dose ipilimumab, then surgery","enrolled":115,"enrolledNote":"ClinicalTrials.gov lists an estimated 353 participants for the amended NICHE protocol, which is still recruiting to further cohorts; the NEJM 2024 NICHE-2 analysis enrolled 115 patients, 111 of them in the efficacy analysis.","enrolledBasis":"registered"},{"id":"azur-1","name":"AZUR-1","route":"/trials/azur-1/","outcomes":[{"endpoint":"Sustained clinical complete response at 12 months (independent central review)","primary":true,"unit":"%","arms":[{"name":"Dostarlimab monotherapy (single arm)","note":"Primary endpoint met at the interim analysis per the sponsor (13 July 2026); the rate itself is pending congress presentation. Single-arm registrational phase 2."}],"source":"https://www.cancernetwork.com/view/dostarlimab-yields-sustained-complete-responses-in-dmmr-msi-h-rectal-cancer"}],"setting":"Untreated stage II/III dMMR/MSI-H locally advanced rectal cancer: dostarlimab monotherapy for 6 months, no surgery or radiation if complete response","enrolled":154,"enrolledBasis":"registry"},{"id":"sano","name":"SANO","route":"/trials/sano/","outcomes":[{"endpoint":"Overall survival at 2 years (non-inferiority)","primary":true,"arms":[{"name":"Active surveillance","n":156},{"name":"Standard surgery","n":118}],"hr":1.14,"ci":[0.74,1.78],"p":"0.55","source":"https://www.sciencedirect.com/science/article/abs/pii/S1470204525000270"}],"setting":"Oesophageal cancer with clinical complete response after CROSS chemoradiation: active surveillance (surgery only on regrowth) vs standard surgery","enrolled":309,"enrolledNote":"ClinicalTrials.gov lists 776 participants (actual); the Lancet Oncology 2025 paper reports 1,115 individuals screened and 309 included in the analysis (198 active surveillance, 111 standard surgery).","enrolledBasis":"analysed"},{"id":"estimabl2","name":"ESTIMABL2","route":"/trials/estimabl2/","outcomes":[{"endpoint":"Patients without events at 3 years","primary":true,"unit":"%","arms":[{"name":"No radioiodine","value":95.6},{"name":"Radioiodine 1.1 GBq","value":95.9}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2111953"}],"setting":"Low-risk differentiated thyroid cancer (pT1a-T1b N0/Nx) after total thyroidectomy: no radioiodine vs 1.1 GBq ablation","enrolled":776,"enrolledBasis":"registry"},{"id":"mars-2","name":"MARS 2","route":"/trials/mars-2/","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Surgery + chemotherapy","n":169,"value":19.3},{"name":"Chemotherapy alone","n":166,"value":24.8}],"hr":1.28,"ci":[1.02,1.6],"source":"https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(24)00119-X/fulltext"}],"setting":"Resectable pleural mesothelioma: extended pleurectomy/decortication + chemotherapy vs chemotherapy alone","enrolled":335,"enrolledBasis":"registry"}],"papers":[]},{"era":"2010s-2026","title":"Treating through a needle or a catheter","description":"Interventional oncology destroys tumours with heat, cold, electric pulses or focused sound, and delivers chemotherapy or radioactive beads through the artery that feeds a liver tumour. EMERALD-1 added immunotherapy to chemoembolisation; OVHIPEC-1 showed that washing the abdomen with heated chemotherapy during ovarian surgery extends survival; liver transplantation cures selected liver cancers and the disease underneath them. Histotripsy, which destroys tissue mechanically with sound, gained approval in the liver and is now being tested as an immune primer.","status":"current","refs":[{"id":"thermal-ablation","kind":"technology","name":"Thermal ablation (RFA, microwave, cryo)","route":"/technologies/thermal-ablation/","status":"standard-of-care","tldr":"Thermal ablation kills a tumour with heat or cold delivered through a needle, with no incision required."},{"id":"irreversible-electroporation","kind":"technology","name":"Irreversible electroporation (NanoKnife)","route":"/technologies/irreversible-electroporation/","status":"established","tldr":"Irreversible electroporation uses short high-voltage pulses that punch permanent holes in tumour cells while sparing nearby vessels and ducts."},{"id":"hifu-histotripsy","kind":"technology","name":"Focused ultrasound & histotripsy","route":"/technologies/hifu-histotripsy/","status":"established","tldr":"Destroying tumours from outside the body with tightly focused sound waves, using either heat or microscopic bubbles."},{"id":"tace","kind":"technology","name":"Transarterial chemoembolisation (TACE)","route":"/technologies/tace/","status":"standard-of-care","tldr":"A catheter threaded into the artery feeding a liver tumour delivers chemotherapy and then blocks the vessel, starving the tumour from inside."},{"id":"radioembolisation-tare","kind":"technology","name":"Radioembolisation (TARE / SIRT, yttrium-90)","route":"/technologies/radioembolisation-tare/","status":"established","tldr":"Millions of tiny radioactive glass or resin beads are injected into the liver artery, lodging in the tumour and irradiating it from within."},{"id":"emerald-1","kind":"trial","name":"EMERALD-1","route":"/trials/emerald-1/","status":"mixed","tldr":"The first trial to show that adding immunotherapy and an anti-VEGF drug to TACE delays progression in intermediate-stage liver cancer."},{"id":"hipec","kind":"technology","name":"HIPEC / PIPAC (intraperitoneal chemotherapy)","route":"/technologies/hipec/","status":"established","tldr":"Washing the abdominal cavity with heated chemotherapy during surgery to kill microscopic peritoneal deposits."},{"id":"ovhipec-1","kind":"trial","name":"OVHIPEC-1","route":"/trials/ovhipec-1/","status":"positive","tldr":"Washing the abdomen with heated chemotherapy during interval surgery extended survival by about a year."},{"id":"liver-transplant-oncology","kind":"technology","name":"Liver transplantation for cancer (Milan criteria and beyond)","route":"/technologies/liver-transplant-oncology/","status":"standard-of-care","tldr":"Replacing the whole diseased liver cures both the cancer and the cirrhosis underneath it, for patients whose tumours are small enough."},{"id":"histosonics","kind":"company","name":"HistoSonics","route":"/companies/histosonics/","tldr":"Inventor of histotripsy, non-invasive tumour destruction with focused ultrasound bubbles; acquired for $2.25B in 2025."}],"trials":[{"id":"emerald-1","name":"EMERALD-1","route":"/trials/emerald-1/","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"TACE + durvalumab + bevacizumab","value":15},{"name":"TACE + placebo","value":8.2}],"hr":0.77,"ci":[0.61,0.98]},{"endpoint":"Overall survival","arms":[{"name":"TACE + durvalumab + bevacizumab"},{"name":"TACE + placebo"}],"hr":0.8,"ci":[0.57,1.11]}],"setting":"Embolisation-eligible unresectable HCC: TACE + durvalumab ± bevacizumab vs TACE + placebo","enrolled":616,"enrolledNote":"ClinicalTrials.gov lists 724 participants (actual); the Lancet 2025 paper reports 887 patients screened and 616 randomised (204, 207 and 205 across the three arms).","enrolledBasis":"randomised"},{"id":"ovhipec-1","name":"OVHIPEC-1","route":"/trials/ovhipec-1/","outcomes":[{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Surgery + HIPEC","n":122,"value":45.7},{"name":"Surgery alone","n":123,"value":33.9}],"hr":0.67,"ci":[0.48,0.94],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1708618"}],"setting":"Stage III ovarian cancer at interval cytoreductive surgery after neoadjuvant chemotherapy: HIPEC with cisplatin vs surgery alone","enrolled":245,"enrolledBasis":"registry"}],"papers":[]},{"era":"2026-2030","title":"Seeing the margin and preparing the patient","description":"Fluorescent dyes that light up tumour and nerves, and portable sequencers that classify a brain tumour's methylation during the operation, aim to make the margin visible rather than guessed. After surgery, ctDNA testing says whether anything was left. Before it, four weeks of exercise, nutrition and psychological preparation (PREHAB) cut complications, and geriatric co-management does the same for older patients; both are proven and both are rarely funded. Sentinel node mapping is extending to cervical (SENTICOL III) and endometrial cancer to spare women lymphoedema.","status":"emerging","refs":[{"id":"fluorescence-guided-surgery","kind":"technology","name":"Fluorescence-guided surgery","route":"/technologies/fluorescence-guided-surgery/","status":"established","tldr":"Injecting a dye that makes tumour glow so the surgeon can see exactly where to cut."},{"id":"optical-imaging","kind":"technology","name":"Optical & fluorescence imaging","route":"/technologies/optical-imaging/","status":"established","tldr":"Dyes that glow under special light, so surgeons can see tumour edges and nerves in the operating theatre."},{"id":"oxford-nanopore","kind":"company","name":"Oxford Nanopore Technologies","route":"/companies/oxford-nanopore/","tldr":"Portable and high-throughput nanopore sequencing, used for rapid intraoperative brain-tumour classification and structural variant detection."},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/","status":"established","tldr":"An ultra-sensitive blood test after surgery that detects leftover cancer months before a scan would."},{"id":"prehabilitation","kind":"technology","name":"Prehabilitation before cancer surgery","route":"/technologies/prehabilitation/","status":"emerging","tldr":"Prehabilitation is a few weeks of structured exercise, nutrition and psychological preparation between diagnosis and surgery to make patients fitter for the operation and speed recovery."},{"id":"prehab-trial","kind":"trial","name":"PREHAB: multimodal prehabilitation before colorectal cancer surgery","route":"/trials/prehab-trial/","status":"positive","tldr":"PREHAB showed that four weeks of supervised training, protein and support before bowel cancer surgery cut severe complications and sped recovery, in an international randomised trial of 251 patients."},{"id":"eras-perioperative-nutrition","kind":"technology","name":"Enhanced recovery (ERAS) and perioperative nutrition","route":"/technologies/eras-perioperative-nutrition/","status":"standard-of-care","tldr":"Instead of starving patients before and after an operation, modern surgical pathways feed them early, give carbohydrate drinks the night before, and get them walking the next day. Complications and hospital stays fall."},{"id":"idea-bio2-prehabilitation-standard","kind":"idea","name":"Four weeks of training and nutrition before major cancer surgery, as standard","route":"/ideas/idea-bio2-prehabilitation-standard/","tldr":"Getting fitter and better nourished before an operation reduces complications and speeds recovery. It is cheap, but only a few hospitals do it."},{"id":"idea-acc-geriatric-co-management-surgery","kind":"idea","name":"Geriatrician co-management for older patients having cancer surgery","route":"/ideas/idea-acc-geriatric-co-management-surgery/","tldr":"When a geriatrician co-manages patients over 75 around a cancer operation, as in the POSH programme at Duke and POPS in the UK, complications, delirium, length of stay and readmissions fall. Preoperative optimisation and postoperative geriatric review should be a standard part of surgical oncology pathways for this age group."},{"id":"idea-acc-prehabilitation-older-surgery","kind":"idea","name":"Multimodal prehabilitation for older patients before major cancer surgery","route":"/ideas/idea-acc-prehabilitation-older-surgery/","tldr":"A few weeks of exercise, nutrition and mental preparation before a big operation helps older patients recover faster and with fewer complications. It costs little and should be routine."},{"id":"senticol-iii","kind":"trial","name":"SENTICOL III","route":"/trials/senticol-iii/","status":"active","tldr":"Tests whether removing only the first draining lymph nodes is safe enough to spare women the lymphoedema of full node removal."},{"id":"intraoperative-radiotherapy","kind":"technology","name":"Intraoperative radiotherapy (IORT)","route":"/technologies/intraoperative-radiotherapy/","status":"established","tldr":"Giving a single large dose of radiation directly to the tumour bed during surgery, with normal organs moved out of the way; used mainly in breast cancer as an alternative to weeks of external radiotherapy."}],"trials":[{"id":"prehab-trial","name":"PREHAB: multimodal prehabilitation before colorectal cancer surgery","route":"/trials/prehab-trial/","outcomes":[{"endpoint":"Severe postoperative complications (Comprehensive Complication Index > 20)","primary":true,"unit":"%","arms":[{"name":"Multimodal prehabilitation","n":123,"value":17.1,"note":"Odds ratio 0.47 (95% CI 0.26-0.87)"},{"name":"Standard care (ERAS)","n":128,"value":29.7}],"p":"0.02","source":"https://doi.org/10.1001/jamasurg.2023.0198"},{"endpoint":"Medical complications","unit":"%","arms":[{"name":"Multimodal prehabilitation","value":15.4,"note":"Odds ratio 0.48 (95% CI 0.26-0.89)"},{"name":"Standard care (ERAS)","value":27.3}],"p":"0.02","source":"https://doi.org/10.1001/jamasurg.2023.0198"},{"endpoint":"6-minute walking distance at 4 weeks post-operatively (change from baseline)","primary":true,"arms":[{"name":"Multimodal prehabilitation","note":"Mean difference 15.6 m (95% CI -1.4 to 32.6); not significant. Trial stopped early because of COVID-19."},{"name":"Standard care (ERAS)"}],"p":"0.07","source":"https://doi.org/10.1001/jamasurg.2023.0198"}],"setting":"Non-metastatic colorectal cancer scheduled for elective resection within an ERAS pathway: 4-week supervised multimodal prehabilitation (high-intensity exercise, nutrition, psychological support, smoking cessation) vs ERAS alone","enrolled":251,"enrolledBasis":"registry"}],"papers":[]},{"era":"What sets the pace","title":"Funding, workforce and access","description":"Surgery and radiotherapy cure more people than drugs but attract a small share of trial funding, so questions like how much to remove, when to operate and whether to operate at all wait years for an answer. Most of the world lacks timely, safe cancer surgery, and the surgeons and anaesthetists to provide it. Standing pre-surgery platform trials, default prehabilitation, and opportunistic salpingectomy during any pelvic operation are among the answers already on the table.","status":"current","refs":[{"id":"b-surgery-radiation-innovation","kind":"bottleneck","name":"Surgery and radiotherapy cure most, get least","route":"/bottlenecks/b-surgery-radiation-innovation/","tldr":"Surgery and radiotherapy cure more people than drugs do, but attract a fraction of the research investment."},{"id":"b-workforce","kind":"bottleneck","name":"Not enough oncologists, nurses, pathologists, physicists","route":"/bottlenecks/b-workforce/","tldr":"The number of people with cancer is rising faster than the workforce trained to treat them."},{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/","tldr":"Seven in ten cancer deaths happen in low- and middle-income countries, where radiotherapy, pathology, surgery and drugs are scarce."},{"id":"b-aging-comorbidity","kind":"bottleneck","name":"Older and multimorbid patients are excluded and undertreated","route":"/bottlenecks/b-aging-comorbidity/","tldr":"Most people with cancer are over 65 but most trial patients are younger and fitter. We guess how to treat the majority."},{"id":"idea-tr2-neoadjuvant-combo-platform","kind":"idea","name":"Pre-surgery platform trials that test combinations on pathological response in months","route":"/ideas/idea-tr2-neoadjuvant-combo-platform/","tldr":"Give drug combinations before surgery and measure how much tumour remains at resection; that answer arrives in months. A standing neoadjuvant platform with a shared control arm, as I-SPY 2 runs in breast cancer, would test combinations quickly in lung, bladder, melanoma, head and neck and oesophago-gastric cancer."},{"id":"idea-prev-opportunistic-salpingectomy-default","kind":"idea","name":"Remove the fallopian tubes during any pelvic surgery once childbearing is finished","route":"/ideas/idea-prev-opportunistic-salpingectomy-default/","tldr":"Most ovarian cancers start in the fallopian tubes. Removing the tubes at hysterectomy, or instead of tying them, as British Columbia has done, appears to prevent ovarian cancer."}],"trials":[],"papers":[]}],"watch":[]}