Surgery
SANO
ForLocally advanced oesophageal cancer, cCR after nCRT
TL;DR5y OS 50% vs 54%, HR 1.17 (0.77-1.77) active surveillance vs surgery after cCR to nCRT; distant mets 46% vs 29%, P<.01.
The RT read is that nCRT alone was the definitive treatment for 43% of the surveillance arm, but distant mets rose to 46% vs 29% without immediate surgery. That makes cCR after nCRT a reasonable organ-preservation endpoint for selected pts. Whether early oesophagectomy suppresses distant spread, or the gap comes from how surveillance detects disease, is the open question.
In locally advanced oesophageal cancer with cCR on biopsies, EUS and PET-CT after nCRT, this supports active surveillance with surgery as needed as a discussable option; it does not address pts without cCR or nCRT regimens other than those used in SANO. The longer read
nCRT alone was definitive treatment for a large part of the surveillance arm, which makes cCR on biopsies, EUS and PET-CT the decision gate. The nCRT regimen is not stated in source, so dose transfer cannot be judged, and the distant-mets excess (46% vs 29%) matters when counselling responders.
Surgery as needed spared 85/198 (43%) a non-beneficial oesophagectomy with no significant 5y OS difference (HR 1.17). The distant-mets excess under surveillance (P<.01) raises the question of whether delaying resection gives up systemic control, and that 43% includes pts who progressed within 6 mo.
9 details 1 trial watching
Multicentre stepped-wedge cluster-randomised non-inferiority trial, 2017-2021, Netherlands Trial Register NTR-6803. This report covers 5y outcomes at median f/u 76 mo (IQR 67-86).
Locally advanced oesophageal cancer with a complete clinical response after nCRT, defined as no tumour on endoscopic biopsies, endoscopic ultrasound, or PET-CT. N=309: 198 active surveillance, 111 standard surgery.
nCRT was the common backbone. The regimen, dose and fractionation are not stated in source, so whether the result transfers to a given chemoRT protocol cannot be judged from this abstract.
The earlier report showed non-inferiority on two-year OS with improved QoL under surveillance. This analysis compares 5y OS and DFS by Cox regression and estimates distant metastasis incidence with competing-risk analysis.
OS and DFS were not significantly different, but distant mets were higher under surveillance (P<.01). 85/198 (43%) were spared non-beneficial oesophagectomy.
| Endpoint | Active surveillance (n=198) | Standard surgery (n=111) | Effect |
|---|---|---|---|
| 5y OS | 50% (95%CI 34-57) | 54% (95%CI 46-64) | HR 1.17 (95%CI 0.77-1.77) |
| DFS | not reported per arm | not reported per arm | HR 1.39 (95% CI 0.94-2.06) |
| 5y cumulative incidence distant mets | 46% (95%CI 39-53) | 29% (95%CI 21-37) | P<.01 |
This extends SANO's own 2y non-inferiority result and follows the preSANO cCR-assessment framework. It parallels the watch-and-wait paradigm in rectal cancer (OPRA). The randomised definitive-CRT question is being tested separately in NEEDS.
The 43% spared figure counts pts with distant mets within 6 mo of nCRT, which inflates the organ-preservation benefit. At 5y, no NI margin is reported, and an OS HR upper bound of 1.77 cannot exclude clinically relevant harm.
Survival parity holds at 5y, but the distant-mets excess is the signal to explain. It could reflect micrometastatic seeding during delayed resection, or disease surfacing on surveillance imaging that resection would have found later. The abstract cannot separate the two.
Long-term f/u of a cluster-randomised NI trial supporting emerging organ preservation; wide OS CI and a significant distant-mets excess stop short of practice-changing.
- Why are distant metastases higher under active surveillance?
- Does systemic therapy during surveillance offset the distant-mets excess? recruiting An Organ Preservation Strategies After Chemoradiotherapy Combined With Immunotherapy for Esophageal Cancer (PALACE3). Phase 3n=356 · primary completion 2028-03 · ph3 nCRT+IO organ preservation vs nCRT+surgery, 3y OS
- Which nCRT regimen maximizes durable cCR?
📚 Sources · 📄 2 papers
Abstract
Abstract
PROTEUS
ForHigh-risk prostate cancer, perioperative setting
TL;DR5-yr BCR-FS 44%, MFS 71%, CSS 92% at 60-mo median f/u in a real-world high-risk prostate cancer benchmark cohort.
7 details 1 trial watching
Design not stated in source; described as a real-world benchmark. Median follow-up 60 mo.
Reported: 5-yr BCR-FS, 5-yr MFS, 5-yr CSS. No primary endpoint or effect size stated.
Framed as a reference point for perioperative treatment strategies in high-risk disease, not a test of one. Useful only once the cohort definition and treatments received are known, since those determine which trial populations it can benchmark.
| Endpoint | 5-yr estimate |
|---|---|
| BCR-FS | 44% |
| MFS | 71% |
| CSS | 92% |
Descriptive benchmark with no comparator, N, eligibility, or treatment details in source; cannot classify impact on any perioperative decision.
- Which perioperative strategies improve on this BCR-FS benchmark? active COACTION Trial - COmbination Androgen bloCkade in inTermediate to hIgh-risk prOstate caNcer Phase 4n=144 · primary completion 2026-03 · RCT neoadjuvant leuprorelin+darolutamide pre-RP, pCR EP
- Cohort high-risk definition and treatments received
📚 Sources · 🐦 1 tweet
🔹 Median follow-up: 60 mo
— Can Aydogdu (@CanDAydogdu) August 28, 2026
🔹 5-yr BCR-FS: 44%
🔹 5-yr MFS: 71%
🔹 5-yr CSS: 92%
Providing a real-world benchmark to contextualize perioperative treatment strategies in this high-risk population.
📄 https://t.co/NyszMg9uCA#ProstateCancer #PROTEUS #Urology
NSABP B-35 margin-width analysis
ForPostmenopausal HR+ DCIS after lumpectomy, WBI and 5yr endocrine therapy
5.6% vs 4.0%
1mm cutoff, absolute difference 1.6%; 2mm cutoff 5.3% vs 3.8%
TL;DR10yr IBTR 5.6% vs 4.0% at 1mm cutoff (abs diff 1.6%), 5.3% vs 3.8% at 2mm (abs diff 1.5%).
Reported via The ASCO Post →
The RT-relevant read is that every patient here got whole-breast irradiation plus 5 years of endocrine therapy, so the 1.5% to 1.6% margin penalty is the residual after full adjuvant treatment. That gates transfer: it says nothing about a close margin when RT is omitted or refused, which is where the margin question actually bites.
In a postmenopausal woman with HR+ DCIS whose lumpectomy margin is under 2mm and who will complete whole-breast RT plus 5yr endocrine therapy, this argues re-excision buys little; it does not extend to premenopausal, HR-negative, or RT-omitted pts. The longer read
Every patient here received whole-breast irradiation with an optional boost plus 5yr endocrine therapy, so 1.5% to 1.6% is the residual margin effect after full adjuvant treatment. Boost use by margin group is not reported in source, which matters: it determines whether a close margin was tolerated or quietly compensated.
A margin under 2mm carried a 10yr IBTR of 5.3% vs 3.8% for ≥2mm, an absolute 1.5% penalty, in the largest randomised-trial population yet examined. That directly gates the return-to-theatre decision, though margin width was not randomised and the narrow group is enriched for disease that could not be cleared.
9 details 1 trial watching
Secondary margin-width analysis of NRG Oncology/NSABP B-35, a double-blind randomised trial of tamoxifen vs anastrozole that enrolled 3,104 postmenopausal women 2003-2006. Because local recurrence did not differ between the two endocrine arms, the arms were pooled and margin width analysed across the whole population. Margin data were collected prospectively by participating pathologists.
Postmenopausal women with hormone receptor-positive DCIS treated with lumpectomy. Two overlapping analysis cohorts: n=2,707 with margins classifiable as <1mm (close/indefinite) vs ≥1mm, and n=2,546 with the closest margin measured, permitting a <2mm vs ≥2mm cutoff.
All patients received whole-breast irradiation with an optional boost. Dose, fractionation and boost uptake are not reported in the source, so the RT exposure behind these recurrence rates cannot be characterised beyond "whole breast, boost optional".
Primary endpoint of interest: cumulative incidence of ipsilateral breast tumor recurrence at 10 years, analysed at both the 1mm and 2mm cutoffs. A secondary analysis of all breast cancer events, including contralateral disease, was also performed.
The prevailing 2mm threshold rests largely on the SSO/ASTRO/ASCO DCIS consensus, whose meta-analytic base drew heavily on series with variable and often absent adjuvant therapy. This analysis puts the same question to a uniformly irradiated, uniformly endocrine-treated randomised trial population, which is why the residual margin effect looks so much smaller.
Margin width was not randomised, and patients re-excised on trial carry their final margin, so the narrow-margin group is enriched for disease that could not be cleared. Source reports no hazard ratios, confidence intervals or event counts, and no multivariable adjustment for grade, size, age or boost use.
The claim is that a 1.5% to 1.6% absolute 10-year difference does not justify routine reoperation, which is a value judgment about the trade against anxiety, cosmesis and cost rather than a statistical one. The difference was statistically significant at the 1mm cutoff, so the argument turns on clinical meaningfulness, and a patient who weighs local recurrence heavily could reasonably read the same number differently.
| Cutoff | Narrow margin | Wider margin | Absolute difference |
|---|---|---|---|
| 1 mm | 5.6% (n=502) | 4.0% (n=2,205) | 1.6% |
| 2 mm | 5.3% (n=879) | 3.8% (n=1,667) | 1.5% |
Prospectively collected margin data from a large RCT population directly contests the 2mm re-excision threshold, but the margin comparison itself is non-randomised and abstract-only.
- Does the finding hold when whole-breast RT is omitted? not yet Assessment of Biosignature Classification of DCIS for RadioTherapy Benefit Post Lumpectomy (ABCD RT) Phase 3n=5270 · primary completion 2039-07 · randomises RT omission in biosignature-low DCIS
- Boost use and dose by margin group
- Applicability to premenopausal or HR-negative DCIS
📚 Sources · 📄 1 paper
Abstract
PREPEC
ForSkin- or nipple-sparing mastectomy, therapeutic or risk-reducing, implant reconstruction
79.2 vs 74.3
Difference 4.8 (95% CI 1.0-8.7), p=0.01
TL;DRPre-pectoral implant improved 24-mo BREAST-Q physical well-being (chest) by 4.8 points, but implant loss 21.1% vs 14.5%.
The 4.8-point BREAST-Q gain (1.0 to 8.7) sits against a 5.7-point higher implant loss rate (-2.4 to 13.8), so this is a trade-off, not a win. Source reports no post-mastectomy RT stratification or irradiated subgroup, so whether pre-pectoral holds up under PMRT is untested here.
In women planned for skin- or nipple-sparing mastectomy with implant reconstruction, this supports pre-pectoral placement for patient-reported chest well-being while flagging higher device loss; it does not address women who will need post-mastectomy radiotherapy. The longer read
Nothing in the source stratifies by post-mastectomy RT or reports capsular contracture, so the irradiated implant patient is not addressed. A 21.1% unplanned device loss rate at 24 months without radiation is the baseline to hold in mind when timing chest wall RT around a pre-pectoral reconstruction.
The primary endpoint is met (4.8 points, 1.0 to 8.7, p=0.01) but the prespecified non-inferiority safety hypothesis is not: unplanned device loss or replacement was 21.1% versus 14.5%. This makes plane selection a documented consent conversation about reoperation risk, not a default technique choice.
| IBBR assignment | N | 24-mo LS mean (95% CI) |
|---|---|---|
| Pre-pectoral IBBR | 191 | 79.2 (75.5 - 82.8) |
| Sub-pectoral IBBR | 189 | 74.3 (70.7 - 78.0) |
| Difference | 4.8 (1.0 - 8.7), p=0.01 |
+2 more figures
| Actual IBBR positioning | Unplanned loss/replacement at 24 mo, crude % (n/N) |
|---|---|
| Pre-pectoral IBBR | 21.1% (41 / 194) |
| Sub-pectoral IBBR | 14.5% (27 / 186) |
| Adjusted difference (95% CI) | 5.7 (-2.4 to 13.8) |
9 details
International randomized trial (PREPEC / OPBC-02) of pre-pectoral versus sub-pectoral implant-based breast reconstruction after skin-sparing or nipple-sparing mastectomy. Follow-up to 24 months, with 6 post-randomization patient-reported timepoints.
Women undergoing nipple-sparing or skin-sparing mastectomy in either the therapeutic or risk-reduction setting. Primary analysis included 191 pre-pectoral and 189 sub-pectoral; safety was analysed by actual positioning (194 versus 186).
Primary: long-term patient-reported physical well-being (chest) on BREAST-Q, scored 0 to 100 with higher better. Main secondary safety endpoint: unplanned loss or replacement of expander or implant.
Primary endpoint met; the safety endpoint moved against pre-pectoral placement. See the endpoint tables above.
Unplanned implant or expander loss or replacement at 24 months was 21.1% (41/194) pre-pectoral versus 14.5% (27/186) sub-pectoral, adjusted difference 5.7% (-2.4 to 13.8), which the investigators call inconsistent with the non-inferiority hypothesis.
Longitudinal completion ranged 83-95% and the primary estimate rests on multiple imputation with imputed baseline values, so the 4.8-point difference carries missing-data assumptions on top of its confidence interval. Surgeon and patient blinding is not feasible for a positioning trial, which cuts directly at a patient-reported primary endpoint.
The trial answers the PRO question it asked and simultaneously undercuts the assumption that pre-pectoral placement is device-safe. Whether a 4.8-point BREAST-Q gain is worth a 5.7-point absolute rise in unplanned reoperation is a preference-sensitive decision, not one the trial resolves.
Randomised, prespecified PRO primary endpoint met, but the safety co-read failed its non-inferiority hypothesis, so the trade-off, not the win, is the finding.
- Does pre-pectoral placement hold up under post-mastectomy radiotherapy
- Capsular contracture rates by implant plane
- Durability of the well-being advantage beyond 24 months
📚 Sources · 🐦 1 tweet
📌 Surgical de-escalation of implant-based breast reconstruction after mastectomy for breast cancer treatment or prevention: The international randomized phase I|I
— Elisabetta Bonzano MD, PhD (@to_be_elizabeth) May 30, 2026
PREPEC trial (ОРBC-02).
Presented by Walter Weber ✨#ASCO26 @OncoAlert #OncoAlertAF #BreastCancer pic.twitter.com/WE20JcBQG0
SENOMAC NCT02240472
ForcN0 T1-T3 breast, 1-2 sentinel-node macromets, planned nodal RT
HR 0.89
95% CI 0.66-1.19, P<0.001 for noninferiority (margin 1.44)
TL;DR5yr RFS 89.7% vs 88.7% omitting completion ALND, HR 0.89 (0.66-1.19), noninferior in 1-2 SLN macromets.
The axilla here was irradiated, not left alone: 89.9% vs 88.4% received nodal target volumes, so this validates SLNB plus regional nodal RT, not surgical de-escalation without RT. Untreated non-SLN disease was present in 34.5%, meaning the RT field is carrying real burden. Nodal level doses and volumes are not yet reported.
In cN0 T1-T3 disease with one or two sentinel macrometastases, including mastectomy, T3 and extracapsular extension, this supports omitting completion dissection when regional nodal irradiation is planned; it does not speak to pts in whom nodal RT is being omitted. The longer read
Nodal target volumes were treated in 89.9% vs 88.4%, so the axilla was managed, not observed, and the RT field is covering the 34.5% non-sentinel-node burden the surgery would have removed. Doses and nodal levels are not yet reported, so the trial supports covering the regional nodes without specifying how.
Systemic therapy shares the load: approximately 65% received chemotherapy and 93% endocrine therapy, and 9.9% of dissected pts were upstaged to pN2 with 3.0% pN3, meaning omission removes nodal counts that currently inform adjuvant intensity. Decisions will rest on tumour biology and genomic tools rather than final node count.
Completion dissection can be omitted in the subgroups the earlier trials could not answer: mastectomy (36.7%), T3 (5.5%) and extracapsular extension, with 5yr RFS 89.7% vs 88.7%. The trade is accepting known residual disease, since 34.5% of dissected pts had additional non-sentinel-node metastases and 9.9% were pN2.
13 details 5 trials watching
Prospective randomized phase 3 noninferiority trial, 1:1, 67 hospitals in Sweden, Denmark, Germany, Greece and Italy. 2766 enrolled Jan 2015 to Dec 2021; per-protocol population 2540 (1335 sentinel-node biopsy only, 1205 completion dissection). Median follow-up 46.8 months (range 1.5 to 94.5).
cN0, T1 to T3 breast cancer with one or two sentinel-node macrometastases (>2mm). Preoperative axillary ultrasound was mandatory; suspicious nonpalpable nodes were still eligible even with FNA-confirmed metastasis. Additional micrometastases and extracapsular extension were allowed, and both breast-conserving surgery (63.3% / 64.3%) and mastectomy (36.7% / 35.7%) were eligible. Mean age 61.
RT including nodal target volumes was given to 89.9% (1192/1326) of the sentinel-node-only group and 88.4% (1058/1197) of the dissection group. Whole-breast RT was mandatory after breast-conserving surgery, but the protocol stipulated no specific target volumes or doses, deferring to national guidelines. QA on 1154 plans showed eCRF-to-plan concordance of 99.3% for breast or chest wall and 96.6% for nodal volumes.
Primary: overall survival (switched from breast cancer-specific survival in 2020 on DSMB advice). Prespecified secondary endpoints were recurrence-free survival, breast cancer-specific survival and patient-reported outcomes. Noninferiority required the upper CI bound for recurrence or death below 1.44.
No clinical lymphedema measurements were performed; arm morbidity relies on the LYMPH-ICF, QLQ-C30, QLQ-BR23 and EQ-5D questionnaires at 1, 3, 5 and 10 years. Only 1-year data from a Swedish-Danish subpopulation are published; 3-year data for the whole trial are not yet available.
Consistent with ACOSOG Z0011 and AMAROS, but the authors place SENOMAC alongside AMAROS and OTOASOR rather than Z0011, SINODAR-ONE or POSNOC, because nodal irradiation was routine here. Where the earlier trials enrolled nearly 40% micrometastasis-only pts, one T3 patient between them, and only 248 mastectomies (17.4%) in AMAROS, SENOMAC filled each of those gaps.
Detailed nodal level doses and volumes are not yet reported, so the RT dose actually treating the residual axilla is unquantified. Withdrawal was higher in the dissection arm, reflecting pts' wish to avoid the operation. The ER+/HER2+ subgroup HR of 0.26 (0.07-0.96) rests on 3 versus 10 events among 13 subgroups and should not be read as a real interaction.
The completion dissection arm shows what is being left behind: 34.5% (403/1167) had additional non-sentinel-node metastases, rising to 51.3% with two macrometastases, and 9.9% were upstaged to pN2 with 3.0% pN3. Noninferior recurrence-free survival despite that residual burden is a statement about what systemic therapy plus nodal RT can control, not about the axilla being clean.
| Event | SLNB only (N=1335) | cALND (N=1205) |
|---|---|---|
| Local recurrence | 12 (0.9) | 10 (0.8) |
| Regional recurrence | 6 (0.4) | 6 (0.5) |
| Distant recurrence | 44 (3.3) | 53 (4.4) |
| Death | 62 (4.6) | 69 (5.7) |
| Recurrence or death as first event | 95 (7.1) | 96 (8.0) |
CONSORT flow
Prespecified noninferiority met with wide margin to boundary; enrolls the mastectomy, T3 and ECE subgroups Z0011 and AMAROS excluded, resolving the residual uncertainty.
- Nodal RT target volumes and doses needed for this result n=1900 · primary completion 2026-07 · axillary treatment vs none, 1-2 SLN macrometsrecruiting The T-REX Trial: Tailored Regional External Beam Radiotherapy in Clinically Node-negative Breast Cancer Patients With 1-2 Sentinel Node Macrometastases. Phase NAn=1350 · primary completion 2028-12 · omits regional RT in ER+ 1-2 SLN macrometsrecruiting Level I-II Axillary Irradiation in Breast Cancer With Sentinel-Node Macro-metastases Phase NAn=1608 · primary completion 2032-12 · level I-II axilla vs whole regional RT, SLN macromets
- Late recurrence in luminal disease beyond 5 years
- Arm morbidity: 3yr and 5yr lymphedema outcomes recruiting Axillary Management in Breast Cancer Patients With Needle Biopsy Proven Nodal Metastases After Neoadjuvant Chemotherapy Phase NAn=1900 · primary completion 2030-02 · 5y lymphedema endpoint after omitting ALND + ARTnot yet Omission of Axillary Lymph Node Dissection in Case of Tumor Spread to Lymph Nodes in the Armpit in Breast Cancer Phase NAn=1380 · primary completion 2030-12 · TAD vs ALND, arm lymphedema + shoulder function