cN Stage Research Articles

Staging fluorodeoxyglucose positron emission tomography/computed tomography for muscle-invasive bladder cancer: a nationwide population-based study.

To provide insight into the use and staging information on lymph-node involvement added by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with muscle-invasive bladder cancer (MIBC), based on a nationwide population-based cohort study. We analysed a nationwide cohort of patients with MIBC without signs of distant metastases, newly diagnosed in the Netherlands between November 2017 and October 2019. From this cohort, we selected patients who underwent pre-treatment staging with CT only or CT and FDG-PET/CT. The distribution of patients, disease characteristics, imaging findings, nodal status (clinical nodal stage cN0 vs cN+) and treatment were described for each imaging modality group (CT only vs CT and FDG-PET/CT). We identified 2731 patients with MIBC: 1888 (69.1%) underwent CT only; 606 (22.2%) underwent CT and FDG-PET/CT, 237 (8.6%) underwent no CT. Of the patients who underwent CT only, 200/1888 (10.6%) were staged as cN+, vs 217/606 (35.8%) who underwent CT and FDG-PET/CT. Stratified analysis showed that this difference was found in patients with clinical tumour stage (cT)2 as well as cT3/4 MIBC. Of patients who underwent both imaging modalities and were staged with CT as cN0, 109/498 (21.9%) were upstaged to cN+ based on FDG-PET/CT. Radical cystectomy (RC) was the most common treatment within both imaging groups. Preoperative chemotherapy was more frequently applied in cN+ disease and in FDG-PET/CT-staged patients. Concordance of pathological N stage after upfront RC was higher among patients staged as cN+ with CT and FDG-PET/CT (50.0% pN+) than those staged as cN+ with only CT (39.3%). Patients with MIBC who underwent pre-treatment staging with FDG-PET/CT were more often staged as lymph node positive, regardless of cT stage. In patients with MIBC who underwent CT and FDG-PET/CT, FDG-PET/CT led to clinical nodal upstaging in approximately one-fifth. Additional imaging findings may influence subsequent treatment strategies.

Neoadjuvant chemotherapy (NAC) followed by total mesorectal excision (TME) and adjuvant chemotherapy versus TME followed by adjuvant chemotherapy in very low-lying clinical (c) T3 rectal cancer (NAIR): A multicenter, randomized, open-label, phase 2/3 trial.

3519 Background: Chemoradiotherapy and total neoadjuvant therapy are the standard treatments for locally advanced rectal cancer (LARC). Although radiotherapy (RT) is an integral part of treatment, it negatively impacts anal function after TME for cases of very low-lying LARCs. This trial examined the efficacy, safety, and influence on postoperative anal function of NAC without RT in patients (pts) with very low-lying cT3 LARCs. Methods: Pts with cT3N0-2M0 adenocarcinomas located within 5 cm from the anal verge, whose anuses were expected to be preserved, were randomly assigned (1:1) to either the NAC group (preoperative chemotherapy with six cycles of mFOLFOX6 or four cycles of CAPOX followed by TME; then, postoperative identical regimen) or the TME group (upfront TME followed by postoperative chemotherapy with 12 cycles of mFOLFOX6 or 8 cycles of CAPOX), stratified by cN stage, center, and sex. The primary endpoint was the 3-year recurrence-free survival (RFS), which was compared between groups using a stratified log-rank test at a one-sided alpha level of 20%. Results: Between February 2013 and March 2019, 130 pts were enrolled and randomly assigned to a treatment group. A total of 127 pts were evaluable (65 in the NAC group and 62 in the TME group). All but one patient with early progression completed preoperative chemotherapy in the NAC group, and all pts in both groups underwent TME. After a median follow-up of 37.4 months (IQR 36.5-40.5), the 3-year RFS was 75.5% (95% CI 62.5-84.5) in the NAC group vs. 70.9% (95%CI 57.2-80.9) in the TME group (hazard ratio 0.67, 95% CI 0.34-1.32; P = 0.098), and the primary endpoint was met. There were no differences in the occurrence of grade 3 or higher postoperative complications (20% in the NAC group vs. 21% in the TME group [P = 1.000]), chemo-associated grade 3 or higher adverse events (28% in the NAC group vs. 23% in the TME group [P = 0.551]), or any grade of peripheral sensory neuropathy lasting for 3 years (22.7% in the NAC group vs. 38.5% in the TME group in pts treated with mFOLFOX6 [P = 0.3163], 7.1% in the NAC group vs. 33.3% in the TME group in pts treated with CAPOX [P = 0.1038]), between the groups. No treatment-related deaths occurred in either of the groups. At 3 years after randomization, 61 pts in the NAC group (93.8%) and 52 pts in the TME group (83.9%) could defecate via their anuses (P = 0.092). The median Wexner incontinence score was 11.0 in the NAC group and 10.0 in the TME group (P = 0.3405). Conclusions: For pts with very low-lying cT3 LARC, NAC followed by TME and adjuvant chemotherapy achieved significantly better RFS and anus-preserving rates compared to upfront TME followed by adjuvant chemotherapy, without deteriorating postoperative complications or postoperative anal function. Clinical trial information: UMIN000009510 .

Oncologic safety of breast conservation following NACT in women with locally advanced breast cancer.

Breast conservation surgery (BCS) is the accepted standard of treatment for early breast cancer, with evidence from randomized controlled and population-based studies. The oncological outcome of BCS in locally advanced breast cancer (LABC) is mainly available from retrospective series with a small sample size and a shorter follow-up duration. A retrospective observational study of 411 non-metastatic LABC patients who received neoadjuvant chemotherapy (NACT) followed by surgery from 2011 to 2016. We retrieved the data from a prospectively maintained database and electronic medical records. Survival data were analyzed by Kaplan-Meier curves and Cox regression using Statistical Package for the Social Sciences 25 and STATA 14. 146/411 (35.5%) women had BCS with a margin positivity rate of 3.42%. With a median follow-up of 64 months (IQR 61, 66), the local relapse rate was 8.9% in BCS and 8.3% after mastectomy. The estimated 5-year locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS) rates of BCS were 86.9%, 63.9%, 71% and 79.3%, and 90.1%, 57.9%, 58.3% and 71.5% in the mastectomy group. On univariate analysis, BCS showed superior survival outcomes compared to mastectomy (unadjusted HR (95% CI) for RFS: 0.70 (0.50-1), DDFS: 0.57 (0.39-0.84), OS: 0.58 (0.36-0.93)). After adjusting for age, cT stage, cN stage, poorer chemotherapy response (ypT0/is, N0) and radiotherapy, BCS and mastectomy groups were found comparable in terms of LRFS (HR: 1.1, 0.53-2.3), DDFS (HR: 0.67, 0.45-1.01), RFS (HR: 0.80, 0.55-1.17) and OS (HR: 0.69, 0.41-1.14). BCS is technically feasible in LABC patients. LABC patients who respond well to NACT can be offered BCS without compromising survival outcomes.

Computed tomography-based radiomics nomogram for the pre-operative prediction of BRAF mutation and clinical outcomes in patients with colorectal cancer: a double-center study.

To develop and validate a radiomics nomogram based on CT for the pre-operative prediction of BRAF mutation and clinical outcomes in patients with colorectal cancer (CRC). A total of 451 CRC patients (training cohort = 190; internal validation cohort = 125; external validation cohort = 136) from 2 centers were retrospectively included. Least absolute shrinkage and selection operator regression was used to select radiomics features and the radiomics score (Radscore) was calculated. Nomogram was constructed by combining Radscore and significant clinical predictors. Receiver operating characteristic curve analysis, calibration curve and decision curve analysis were used to evaluate the predictive performance of the nomogram. Kaplan‒Meier survival curves based on the radiomics nomogram were used to assess overall survival (OS) of the entire cohort. The Radscore consisted of nine radiomics features which were the most relevant to BRAF mutation. The radiomics nomogram integrating Radscore and clinical independent predictors (age, tumor location and cN stage) showed good calibration and discrimination with AUCs of 0.86 (95% CI: 0.80-0.91), 0.82 (95% CI: 0.74-0.90) and 0.82 (95% CI: 0.75-0.90) in the training cohort, internal validation and external validation cohorts, respectively. Furthermore,the performance of nomogram was significantly better than that of the clinical model (p < 0.05). The radiomics nomogram-predicted BRAF mutation high-risk group had a worse OS than the low-risk group (p < 0.0001). The radiomics nomogram showed good performance in predicting BRAF mutation and OS of CRC patients, which could provide valuable information for individualized treatment. The radiomics nomogram could effectively predict BRAF mutation and OS in patients with CRC. High-risk BRAF mutation group identified by the radiomics nomogram was independently associated with poor OS.

Penile cancer: long-term infectious and thromboembolic complications following lymph node dissection – a population-based study (Sweden)

Purpose To assess the long-term risks of infectious and thromboembolic events following inguinal (ILND) and pelvic (PLND) lymph node dissection in men with penile cancer. Material and methods A total of 364 men subjected to ILND with or without PLND for penile cancer between 2000 and 2012 were identified in the Swedish National Penile Cancer Register. Each patient was matched based on age and county of residence with six penile cancer-free men. The Swedish Cancer Register and other population-based registers were used to retrieve information on treatment and hospitalisation for selected infectious and thromboembolic events. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models with multiple imputation. Results The risk of infectious events remained increased for more than five years postoperatively in men with penile cancer compared with matched controls. The palpable nodal disease was the only predictor of these events, with risk increasing with the cN stage. The HR at one, three and five years and six months postoperatively was 8.60 (95% CI 5.16–14.34), 4.02 (95% CI 2.65–6.09) and 1.93 (95% CI 1.11–3.38), respectively. An increased risk of thromboembolic events persisted for three years postoperatively. The HR at one and three years postoperatively was 13.51 (95% CI 6.53–27.93) and 2.12 (95% CI 1.07–4.20). The results correspond well with the over-prescription of anticoagulants observed during this period. An association with bulky disease (cN3) was observed. Conclusions Lymph node dissection for penile cancer is associated with an increased risk of infectious and thromboembolic events. The findings of this population-based study show that the risks of these events remain increased more than five years for infectious and three years for thromboembolic events. Improved awareness of long-term complications following ILND is of importance both among patients and care givers to ensure early detection and treatment.

PD09-05 STANDARD VERSUS EXTENDED LYMPH NODE DISSECTION AT THE TIME OF RADICAL CYSTECTOMY FOR BLADDER CANCER

You have accessJournal of UrologyCME1 Apr 2023PD09-05 STANDARD VERSUS EXTENDED LYMPH NODE DISSECTION AT THE TIME OF RADICAL CYSTECTOMY FOR BLADDER CANCER Alejandro Abello, Sumedh Kaul, Aaron Fleishman, Joaquim Bellmunt, Irving Kaplan, Simon Kim, Peter Chang, Andrew Wagner, Ruslan Korets, Aria Olumi, and Boris Gershman Alejandro AbelloAlejandro Abello More articles by this author , Sumedh KaulSumedh Kaul More articles by this author , Aaron FleishmanAaron Fleishman More articles by this author , Joaquim BellmuntJoaquim Bellmunt More articles by this author , Irving KaplanIrving Kaplan More articles by this author , Simon KimSimon Kim More articles by this author , Peter ChangPeter Chang More articles by this author , Andrew WagnerAndrew Wagner More articles by this author , Ruslan KoretsRuslan Korets More articles by this author , Aria OlumiAria Olumi More articles by this author , and Boris GershmanBoris Gershman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003240.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: It is uncertain whether lymphadenectomy (LND) provides a survival benefit in patients undergoing radical cystectomy (RC). In the only completed randomized trial on this topic – LEA AUO AB 25/02 – extended LND (eLND) was associated with improved survival compared to limited/standard (sLND), although these associations did not reach statistical significance. Herein, we emulated a pragmatic clinical trial designed to resemble the LEA trial. METHODS: We identified patients in the National Cancer Database who met the following eligibility criteria based on the LEA trial: adult 40-79 years old, Charlson 0-1, underwent RC with LND for high-grade cT1/cT2-T4a cNany cM0 urothelial carcinoma of the bladder from 2006-2015, without neoadjuvant chemotherapy, at a hospital performing ≥16 RC/year. sLND and eLND were defined as removal of 4-11 and ≥12 lymph nodes based on the LEA trial. A propensity score (PS) was estimated for receipt of eLND, and the associations of LND type with overall survival (OS) were evaluated adjusting with inverse probability of treatment weights (IPW). RESULTS: A total of 2248 patients formed the study cohort, including 429 with sLND and 1813 with eLND. Baseline characteristics were well-balanced after PS adjustment. During a median follow-up of 37.5 months, eLND was associated with significantly improved 5-year OS compared to sLND (60% vs 48%; HR 0.72, 95%CI: 0.61-0.85, p<0.01; Figure 1). Effect estimates were consistent across all potential treatment effect modifiers, including cT stage, cN stage, and age (Figure 2). Results were robust in sensitivity analyses that modified the definitions for LND and relaxed the annual RC hospital volume requirement. CONCLUSIONS: In observational analyses designed to emulate a completed clinical trial, eLND was associated with improved OS compared to sLND among patients undergoing RC. Survival and effect estimates were similar to those in the LEA trial but statistically significant due to larger sample size. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e241 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alejandro Abello More articles by this author Sumedh Kaul More articles by this author Aaron Fleishman More articles by this author Joaquim Bellmunt More articles by this author Irving Kaplan More articles by this author Simon Kim More articles by this author Peter Chang More articles by this author Andrew Wagner More articles by this author Ruslan Korets More articles by this author Aria Olumi More articles by this author Boris Gershman More articles by this author Expand All Advertisement PDF downloadLoading ...

MP47-03 TRENDS IN SBRT FOR INOPERABLE RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023MP47-03 TRENDS IN SBRT FOR INOPERABLE RENAL CELL CARCINOMA Benjamin V. Stone, David-Dan Nguyen, Dejan K. Filipas, Muhieddine Labban, Edoardo Beatrici, Alexander P. Cole, Shawn Malone, Christopher J. D. Wallis, Quoc-Dien Trinh, Scott C. Morgan, and Soumyajit Roy Benjamin V. StoneBenjamin V. Stone More articles by this author , David-Dan NguyenDavid-Dan Nguyen More articles by this author , Dejan K. FilipasDejan K. Filipas More articles by this author , Muhieddine Labban Muhieddine Labban More articles by this author , Edoardo BeatriciEdoardo Beatrici More articles by this author , Alexander P. ColeAlexander P. Cole More articles by this author , Shawn MaloneShawn Malone More articles by this author , Christopher J. D. WallisChristopher J. D. Wallis More articles by this author , Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author , Scott C. MorganScott C. Morgan More articles by this author , and Soumyajit RoySoumyajit Roy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003293.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A growing body of evidence suggests that stereotactic body radiotherapy (SBRT) could be an appropriate local treatment strategy for patients with renal cell carcinoma (RCC) who refuse surgery or are medically inoperable, but the degree of uptake of SBRT remains understudied. METHODS: The National Cancer Database was utilized to identify all patients from 2004-2020 with non-metastatic RCC for whom surgery was not performed due to medical comorbidities, age, locally advanced disease, or patient refusal. We evaluated trends over time in the use of radiation to the primary tumor for these patients, and the modality of radiation used. Multivariable logistic regression was used to determine the predictors of SBRT adjusted for baseline demographic and clinical covariates. We used multivariable Cox regression to determine the adjusted association of SBRT with overall survival (OS). RESULTS: There were 10,810 patients with RCC from 2004-2020 who were deemed poor surgical candidates or refused surgery. The proportion receiving radiation to the primary tumor increased from 1.7% from 2004-2009 to 3.3% in 2020 (p=0.02), and the proportion treated with SBRT vs. EBRT increased from 51% in 2004-2009 to 65% in 2020. There was a small but statistically significant increase in the odds of SBRT over time (OR=1.05, 95% CI 1.01-1.09, p=0.008 for each year of diagnosis). Age 70-79, treatment at a non-academic center, treatment in New England (versus Atlantic region) and VA insurance were associated with use of SBRT, while cT2 disease was associated with lower use of SBRT versus cT1 disease (Table 1). SBRT (HR 0.52, 95% CI 0.39-0.71, p<0.001) was associated with a significant OS benefit on multivariable Cox regression analysis adjusted for age, race, ethnicity, treatment setting, cT stage, cN stage, histology, and systemic treatment (Table 2). CONCLUSIONS: Although overall utilization of SBRT is very low in RCC patients who are poor candidates for surgery or who refuse surgery, there seems to be an increasing trend of utilization over time. Use of SBRT was associated with superior OS compared to patients treated with EBRT. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e643 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Benjamin V. Stone More articles by this author David-Dan Nguyen More articles by this author Dejan K. Filipas More articles by this author Muhieddine Labban More articles by this author Edoardo Beatrici More articles by this author Alexander P. Cole More articles by this author Shawn Malone More articles by this author Christopher J. D. Wallis More articles by this author Quoc-Dien Trinh More articles by this author Scott C. Morgan More articles by this author Soumyajit Roy More articles by this author Expand All Advertisement PDF downloadLoading ...

MP46-04 THE IMPACT OF CUMULATIVE SMOKING STATUS ON PERIOPERATIVE MORBIDITY AFTER ROBOT-ASSISTED RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP46-04 THE IMPACT OF CUMULATIVE SMOKING STATUS ON PERIOPERATIVE MORBIDITY AFTER ROBOT-ASSISTED RADICAL CYSTECTOMY Pietro Piazza, Carlo Bravi, Adele Piro, Luca Sarchi, Marco Paciotti, Maria Peraire Lores, Eleonora Balestrazzi, Luigi Nocera, Melle, Belgium, Angelo Mottaran, Federico Piramide, Ruben De Groote, Geert De Naeyer, Frederiek D'hondt, Rui Farinha, Riccardo Schiavina, Eugenio Brunocilla, and Alexandre Mottrie Pietro PiazzaPietro Piazza More articles by this author , Carlo BraviCarlo Bravi More articles by this author , Adele PiroAdele Piro More articles by this author , Luca SarchiLuca Sarchi More articles by this author , Marco PaciottiMarco Paciotti More articles by this author , Maria Peraire LoresMaria Peraire Lores More articles by this author , Eleonora BalestrazziEleonora Balestrazzi More articles by this author , Luigi NoceraLuigi Nocera More articles by this author , Melle Melle More articles by this author , Belgium Belgium More articles by this author , Angelo MottaranAngelo Mottaran More articles by this author , Federico PiramideFederico Piramide More articles by this author , Ruben De GrooteRuben De Groote More articles by this author , Geert De NaeyerGeert De Naeyer More articles by this author , Frederiek D'hondtFrederiek D'hondt More articles by this author , Rui FarinhaRui Farinha More articles by this author , Riccardo SchiavinaRiccardo Schiavina More articles by this author , Eugenio BrunocillaEugenio Brunocilla More articles by this author , and Alexandre MottrieAlexandre Mottrie More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003292.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The objective of this study was to evaluate the impact of cumulative smoking exposure (pack/year) and of time since smoking cessation (>1 year) on perioperative morbidity after robot-assisted radical cystectomy (RARC) for muscle invasive bladder cancer (MIBC). METHODS: We retrospectively evaluated 328 patients treated with RARC for MIBC at OLV hospital (Aalst, Belgium) between 2015 and 2020. All procedures were performed by two highly experienced robotic surgeons. Perioperative morbidity was defined as any post-operative early (<90 days) complications and/or post-operative readmission. Multivariable logistic regressions were performed to explore the effect of smoking status (current vs. former vs. never smoker), cumulative smoking exposure (in pack-years, calculated by multiplying the number of years smoked with the average number of packs per day) and time since smoking cessation on perioperative morbidity after RARC. RESULTS: Overall, 133 (40%), 132 (40%) and 63 (20%) patients were never, former and current smokers respectively. Median age was 71 years (interquartile range [IQR]: 62, 78). No differences were recorded in terms of age, gender, and cT and cN stage (all p>0.05). No significant differences were recorded in terms of urinary diversion (UD, neobladder vs ileal conduit) or UD approach (extra-corporeal vs intra-corporeal). Current smokers had significantly longer smoking duration (43 vs. 30 years; p<0.001) and higher cumulative smoking exposure (35 vs. 30 pack/year; p=0.02) when compared with former smokers. Median time since smoking cessation for former smokers was 15 years (IQR: 8, 27). Overall, 69 (21%) patients were readmitted to the hospital without differences among the three groups. 38 current smokers (60%), 66 former smokers (50%) and 49 never smokers (37%) experienced early post-operative complications (p=0.005). 13 (24%) current smokers, 25 (17%) former smokers and 18 (13%) never smokers experienced more than one early complication. On multivariable analysis, former (odds ratio [OR]: 3.8; 95% confidence interval [CI]: 1.7, 9.3; p=0.002) and current (OR: 6.7; 95%CI: 2.8, 12; p<0.001) smokers had higher odds of perioperative morbidity as compared to patients who never smoked. CONCLUSIONS: Smoking status, time since smoking cessation and cumulative smoking exposure are significantly associated with perioperative morbidity after RARC. Further studies with longer follow-up are awaited to confirm these findings. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e631 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pietro Piazza More articles by this author Carlo Bravi More articles by this author Adele Piro More articles by this author Luca Sarchi More articles by this author Marco Paciotti More articles by this author Maria Peraire Lores More articles by this author Eleonora Balestrazzi More articles by this author Luigi Nocera More articles by this author Melle More articles by this author Belgium More articles by this author Angelo Mottaran More articles by this author Federico Piramide More articles by this author Ruben De Groote More articles by this author Geert De Naeyer More articles by this author Frederiek D'hondt More articles by this author Rui Farinha More articles by this author Riccardo Schiavina More articles by this author Eugenio Brunocilla More articles by this author Alexandre Mottrie More articles by this author Expand All Advertisement PDF downloadLoading ...

MP32-12 ROBOTIC VERSUS OPEN RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER

You have accessJournal of UrologyCME1 Apr 2023MP32-12 ROBOTIC VERSUS OPEN RADICAL CYSTECTOMY FOR UROTHELIAL CARCINOMA OF THE BLADDER Joseph Black, Sumedh Kaul, Aaron Fleishman, Ruslan Korets, Peter Chang, Andrew Wagner, Ma Boston, Simon Kim, Joaquim Bellmunt, Irving Kaplan, Aria Olumi, and Boris Gershman Joseph BlackJoseph Black More articles by this author , Sumedh KaulSumedh Kaul More articles by this author , Aaron FleishmanAaron Fleishman More articles by this author , Ruslan KoretsRuslan Korets More articles by this author , Peter ChangPeter Chang More articles by this author , Andrew WagnerAndrew Wagner More articles by this author , Ma BostonMa Boston More articles by this author , Simon KimSimon Kim More articles by this author , Joaquim BellmuntJoaquim Bellmunt More articles by this author , Irving KaplanIrving Kaplan More articles by this author , Aria OlumiAria Olumi More articles by this author , and Boris GershmanBoris Gershman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003265.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The comparative effectiveness of robotic-assisted (RARC) versus open radical cystectomy (ORC) in the management of urothelial carcinoma of the bladder (UCB) remains uncertain. Limited randomized trial evidence suggests similar perioperative outcomes and 2-year progression-free survival, but long-term survival outcomes and real-world data are lacking. We therefore evaluated the comparative effectiveness of RARC and ORC using a nationwide oncology dataset. METHODS: We conducted observational analyses designed to emulate the complete RAZOR trial using the NCDB. Specifically, we identified adults age 37-89 years with Charlson 0-1 diagnosed with cT1-4 cN0-1 cM0 UCB from 2010-2015 and treated with RARC or ORC with LND at a hospital performing an average of >10 RCs per year. We then examined the associations of surgical approach with perioperative outcomes and overall survival (OS) using propensity score methods with stabilized inverse probability of treatment weights (sIPW), with Cox models further adjusted for imbalanced pathologic features (pT and pN stage). RESULTS: A total of 3,493 patients were included in the cohort, of whom 2,492 (71%) underwent ORC and 1001 (29%) underwent RARC. Median follow-up was 29.5 months. After sIPW reweighting, pre-treatment baseline characteristics were well-balanced. After adjustment, RARC was associated with a statistically significant but clinically insignificant higher lymph node (LN) yield (median 20 vs 18 LNs; p<0.01) and shorter length of hospitalization (median 7 [IQR 5-8] vs 7 [IQR 6-10]; p<0.01), but there were no differences in positive surgical margins (8% vs 8%; p=0.64) or 30-day readmissions (10% vs 9%; p=0.80). After adjustment, there was no difference in OS between RARC and ORC (Figure 1; 5-year OS 57% vs 55%; p=0.28; HR 0.93, 95%CI 0.80-1.07). OS treatment effects were similar when examined across cT stage, cN stage, and age. CONCLUSIONS: In observational analyses designed to emulate the complete RAZOR trial, RARC was not associated with statistically significant differences in positive surgical margins, 30-day readmissions, or OS compared to ORC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e445 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joseph Black More articles by this author Sumedh Kaul More articles by this author Aaron Fleishman More articles by this author Ruslan Korets More articles by this author Peter Chang More articles by this author Andrew Wagner More articles by this author Ma Boston More articles by this author Simon Kim More articles by this author Joaquim Bellmunt More articles by this author Irving Kaplan More articles by this author Aria Olumi More articles by this author Boris Gershman More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract PD12-07: PD12-07 The effect of BMI on the pathological response after neoadjuvant systemic therapy in breast cancer patients: a nationwide retrospective study

Abstract Background: Neoadjuvant systemic therapy is increasingly applied in breast cancer patients to improve surgical and oncological outcomes. There is only limited data from clinical practice on the relevance of body mass index (BMI) on the pathologic complete response (pCR) rate following neoadjuvant systemic treatment (NST). We aimed to retrospectively analyze the impact of BMI on pCR after NST for Dutch breast cancer patients. Methods: Patients diagnosed with invasive breast cancer between 2019 and 2021 who were treated with NST followed by a surgical procedure, were selected from the Netherlands Cancer Registry (NCR). Patients were divided into three groups based on BMI: patients with underweight/normal weight (BMI&amp;lt; 25 kg/m2), patients with overweight (BMI 25-29.9 kg/m2) and patients with obesity (BMI&amp;gt;30 kg/m2). Patients with unknown BMI, ER/PR/HER2 or pCR status were excluded for analysis. The primary outcome was pCR after NST. The association between BMI and pCR was estimated using logistic regression models with the expression of odds ratios (ORs). Results: After applying in- and exclusion criteria, 4430 patients were included for analysis, statified into four molecular breast cancer subtypes; HR+/HER2- (n=2256), HR+/HER2- (n=722), HR-/HER2+ (n=405) and HR-/HER2- (n=1047). The predictors age, differentiation grade, histological type, clinical tumor (cT) and nodal (cN) stage and molecular breast cancer subtype were found siginificant for achieving pCR after NST. Multivariabele regression analysis identified differentiation grade, cT and cN stage and molecular subtype as independent predictors for pCR after NST. There was no association between pCR and (continuous or categorical) BMI. Above mentioned analyses performed by stratification according to molecular breast cancer subtype, also showed no statistically meaningful association between BMI and pCR. Conclusion: In this nationwide retrospective cohort study, evaluating 3340 patients with invasive breast cancer, we found no evidence of BMI being a predictive factor for achieving pCR following NST in neither the whole cohort, nor stratified according to molecular breast cancer subtype. Table 1. Multivariable regression analysis of the total cohort Citation Format: Britt Jansen, Anke Gielen, Mariette Agteroff, Marissa van Maaren, Sandra Beijer, Martine Moossdorff, Marjolein Smidt, Emily Postma. PD12-07 The effect of BMI on the pathological response after neoadjuvant systemic therapy in breast cancer patients: a nationwide retrospective study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD12-07.

Clinicopathological characteristics and treatment outcome of resectable gastric cancer patients with small para-aortic lymph node.

Resectable gastric cancer (GC) patients with small para-aortic lymph node (smaller than 10mm in diameter, sPAN) were seldom reported, and existing guidelines did not provide definite treatment recommendation for them. A total of 667 consecutive resectable GC patients were enrolled. 98 patients were in the sPAN group, and 569 patients without enlarged para-aortic lymph node were in the nPAN group. Standard D2 lymphadenectomy was performed. Neoadjuvant and adjuvant chemotherapy were administrated according to the cTNM and pTNM stage, respectively. Clinicopathological features and prognosis were compared between these two groups. The median size of sPAN was 6 (range, 2-9) mm and the distribution was prevalent in No. 16b1. cN stage (p=0.001) was significantly related to the presence of sPAN. sPAN was both independent risk factor for OS (p=0.031) and RFS (p=0.046) of all patients. The prognosis of patients with sPAN was significantly worse than that of patients with nPAN (OS: p=0.008; RFS: p=0.007). Preoperative CEA and CA19-9 were independent risk factors for prognosis of patients with sPAN. Furthermore, patients in the sPAN group with normal CEA and CA19-9 exhibited acceptable prognosis (5-year OS: 67%; RFS: 64%), while those with elevated CEA or CA19-9 suffered significantly poorer prognosis (5-year OS: 17%; RFS: 17%) than patients in the nPAN group (5-year OS: 64%; RFS 62%) (both p < 0.05). Standard D2 lymphadenectomy should be considered a valid approach for GC patients with sPAN associate to normal preoperative CEA and CA19-9 levels. Patients with sPAN associated to elevated CEA or CA19-9 levels could benefit from a multimodal approach: neoadjuvant chemotherapy; radical surgery with D2 plus lymph nodal dissection extended to No. 16 station.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

MRI-Based Radiomic Models Outperform Radiologists in Predicting Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

The 15%-27% of patients with locally advanced rectal cancer (LARC) achieved pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) and could avoid proctectomy. We aimed to investigate the effectiveness of treatment response prediction using MRI-based pre-, post-, and delta-radiomic features for LARC patients treated with nCRT and to compare these radiomic models with radiologists' visual assessment. A total of 126 patients with LARC who received nCRT before surgery were included and randomly divided into a training set (n=84) and a validation set (n=42). 250 radiomic features were extracted from T2-weighted images from pre- and post-nCRT MRI. Pearson correlation analysis and AONVA or Relief were used to identify radiomic descriptors associated with pCR. Five machine-learning classifiers were compared to construct radiomic models. The radiomic nomogram was built via multivariate logistic regression analysis. Two senior radiologists independently rated tumor regression grades and compared with radiomic models. Area under the curve (AUC) of the models and pooled observers were compared by using the DeLong test. The optimal pre-, post-, and delta-radiomic models yielded an AUC of 0.717 (95% CI: 0.639-0.795), 0.805 (95%CI: 0.736-0.874), and 0.724 (95%CI: 0.648-0.800), respectively. The radiomic nomogram based on pre-nCRT cN stage, pre-nCRT radscore, and post-nCRT radscore achieved an AUC of 0.852 (95%CI: 0.774-0.930), which was higher than the single radiomic models and pooled readers (all p < 0.05). The radiomic nomogram is an effective and invasive tool to predict pCR in LARC patients after nCRT, which outperforms radiologists.

Determinants of pathological complete response to neoadjuvant chemotherapy in breast cancer: A single-institution experience.

Neoadjuvant chemotherapy (NACT) is routinely used in all cases of locally advanced breast cancer and some cases of early breast cancer. We previously reported a pathological complete response (pCR) rate of 8.3%. With the increasing use of taxanes and human epidermal growth factor receptor 2 (HER2)-directed NACT, we conducted this study to understand the current pCR rate and its determinants. A prospective database of breast cancer patients who underwent NACT followed by surgery between January and December 2017 was evaluated. Of the 664 patients, 87.7% were cT3/T4, 91.6% were grade III, and 89.8% were node-positive at presentation (54.4% cN1, 35.4% cN2). The median age was 47 years; median pre-NACT clinical tumor size was 5.5 cm. Molecular subclassification was 30.3% hormone receptor positive (HR+) HER2-, 18.4% HR+HER2+, 14.9% HR-HER2+, and 31.6% triple negative (TN). Both anthracyclines and taxanes were given preoperatively in 31.2% patients whereas 58.5% of HER2 positive patients received HER2-targeted NACT. The overall pCR rate was 22.4% (149/664), 9.3% in HR+HER2-, 15.6% in HR+HER2+, 35.4% in HR-HER2+, and 33.4% in TN. On univariate analysis, duration of NACT ( P < 0.001), cN stage at presentation ( P = 0.022), HR status ( P < 0.001), and lymphovascular invasion ( P < 0.001) were associated with pCR. On logistic regression, HR negative status (Odds ratio [OR] 3.314, P < 0.001), longer duration of NACT (OR 2.332, P < 0.001), cN2 stage (OR 0.57, P = 0.012), and HER2 negativity (OR 1.583, P = 0.034) were significantly associated with pCR. Response to chemotherapy depends on molecular subtype and duration of NACT. A low rate of pCR in the HR+ subgroup of patients warrants reconsideration of neoadjuvant strategies.

Establishing and validating predictive nomograms for lateral pelvic lymph node metastasis in patients with rectal cancer based on radiologic factors and clinicopathologic characteristics

IntroductionIt is critical to accurately predict the occurrence of lateral pelvic lymph node (LPN) metastasis. Currently, verified predictive tools are unavailable. This study aims to establish nomograms for predicting LPN metastasis in patients with rectal cancer who received or did not receive neoadjuvant chemoradiotherapy (nCRT). Materials and methodsWe carried out a retrospective study of patients with rectal cancer and clinical LPN metastasis who underwent total mesorectal excision (TME) and LPN dissection (LPND) from January 2012 to December 2019 at 3 institutions. We collected and evaluated their clinicopathologic and radiologic features, and constructed nomograms based on the multivariable logistic regression models. ResultsA total of 472 eligible patients were enrolled into the non-nCRT cohort (n = 312) and the nCRT cohort (n = 160). We established nomograms using variables from the multivariable logistic regression models in both cohorts. In the non-nCRT cohort, the variables included LPN short diameter, cT stage, cN stage, histologic grade, and malignant features, and the C-index was 0.930 in the training cohort and 0.913 in the validation cohort. In the nCRT cohort, the variables included post-nCRT LPN short diameter, ycT stage, ycN stage, histologic grade, and post-nCRT malignant features, and the C-index was 0.836 in the training dataset and 0.827 in the validation dataset. The nomograms in both cohorts were moderately calibrated and well-validated. ConclusionsWe established nomograms for patients with rectal cancer that accurately predict LPN metastasis. The performance of the nomograms in both cohorts was high and well-validated.

Clinical Efficacy of Intraoperative Ultrasound for Prophylactic Lymphadenectomy of the Lateral Cervical Neck in Stage CN0 Papillary Thyroid Cancer: A Prospective Study

Background: To evaluate the clinical effectiveness of lateral cervical region (LCR) lymphadenectomy as a preventative procedure for stage CN0 papillary thyroid cancer (PTC).Methods: From December 2019 to October 2021, 108 patients with CN0 stage PTC hospitalized to our general surgery department were recruited. After analysis, the clinical data of these patients were separated into two groups: 57 cases were in the Surgical + lymphatic dissection group and 51 instances were in the surgical group. Total thyroidectomy with central node dissection (TTCD) was carried out on the surgical group, whereas intraoperative ultrasound (IOUS) for prophylactic LCR lymph nodes dissection was carried out on the basis of TTCD in the Surgical + lymphatic dissection group. The postoperative complications, cervical lymph node metastases and recurrent reoperation were analyzed in both groups.Results: In the Surgical + lymphatic dissection group, the rate of lymph node metastasis (LNM) identified by IOUS in the LCR of PTC was 29.82% (17/57). In the central group with >2 lymph node metastases compared to the central group with < 2 lymph node metastases, the rate of LCR LNM was considerably greater (20% vs. 43%). Between the two groups, there was no statistically significant difference in the frequency of postoperative complications (P > 0.05). At the 1-year postoperative follow-up, the recurrence rate in the surgical group was 13.73%, whereas there was no recurrence in the Surgical + lymphatic dissection group.Conclusions: The recurrence/reoperation rate of PTC in individuals with stage CN0 can be decreased by IOUS guided prophylactic lymph node dissection in the LCR.

OGC P20 Metabolic tumour and nodal response to neoadjuvant chemotherapy on FDG PET-CT as a predictor of pathological response and survival in patients undergoing surgical resection for locally advanced oesophageal adenocarcinoma

Abstract Background 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) is routinely used for staging of oesophageal cancer and has an emerging role in assessing response to neoadjuvant therapy. Several studies have demonstrated that a reduction in FDG avidity of the primary tumour and loco-regional lymph nodes following neoadjuvant chemotherapy predicts pathological response and survival in this patient group. However, no studies have evaluated the prognostic significance of metabolic parameters with respect to pathological response in lymph nodes. Change in primary tumour maximum standardised uptake value (SUVmax) is the most widely used FDG PET-CT parameter to define metabolic response, with various thresholds described. The most commonly utilised are a 35% reduction in SUVmax (MUNICON), and a 30% reduction in SUVmax (PERCIST). However, there is no consensus regarding the optimal classification; the MUNICON threshold was derived from only 40 patients and PERCIST is not tumour specific. The primary aim of this study was to evaluate the ability of FDG PET-CT to predict pathological response in the primary tumour (pTR) and lymph nodes (pNR) in patients with oesophageal adenocarcinoma undergoing neoadjuvant chemotherapy before surgery. Secondary aims were to assess the prognostic effect of metabolic and pathological response and evaluate the predictive ability of response classifications. Methods Cohort study of 75 patients with locally advanced oesophageal or oesophago-gastric junctional adenocarcinoma who underwent FDG-PET-CT before and after neoadjuvant chemotherapy, prior to surgical resection at Guy's and St Thomas’ NHS Foundation Trust, London, UK, between 2017–2020. SUV metrics related to the primary tumour and loco-regional lymph nodes were derived on pre- and post- treatment FDG PET-CT. pTR and pNR were evaluated using the Mandard classification. Patients with Mandard scores of 1–3 were classified as pathological responders and those with Mandard scores of 4–5 as non-responders. Clinicopathological characteristics were compared using the Chi-squared test. Receiver operator characteristic (ROC) analysis was performed and area under the curve (AUC) calculated to determine optimum SUVmax thresholds for metabolic response in the primary tumour (mTR) and lymph nodes (mNR). Survival curves were created using the Kaplan-Meier method, with subgroups compared using the log-rank test. Survival analysis was performed using Cox proportional hazards regression providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age (continuous), sex (male or female), chemotherapy regimen (ECX or FLOT), cT stage (cT1–2 or cT3–4), cN stage (cN0 or cN+), tumour grade (well / moderately differentiated or poorly differentiated) and presence of signet ring cells (yes or no). Results Mean age was 63 years with the majority male (86.7%). Almost two thirds received FLOT (48/75, 64.0%) with the remainder receiving ECX chemotherapy. There was discordance between pathological response in the primary tumour and lymph nodes in several patients, including 23.1% (6/26) who demonstrated a lymph node response in the absence of a response in the primary tumour. ROC analysis demonstrated an optimum tumour SUVmax decrease of 51.2% for predicting pTR. Using a pragmatic cut-off of 50% this provided better prediction of pTR (AUC 0.714, sensitivity 73.5%, specificity 69.2%, p&amp;lt;0.001) than PERCIST (AUC 0.631, sensitivity 87.8%, specificity 38.5%, p=0.008) and MUNICON (AUC 0.659, sensitivity 85.7%, specificity 46.2%, p=0.003) criteria. ROC analysis demonstrated an optimum nodal SUVmax decrease of 32.6% for predicting pNR or pathological node negativity. Using a pragmatic 30% SUVmax cut-off and excluding metabolically negative nodes, mNR demonstrated high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p=0.010) for predicting pNR. pTR, mTR, pNR and mNR were independent predictive factors for overall survival on adjusted analysis (pTR responder HR 0.10 95% CI 0.03–0.34; mTR responder HR 0.17 95% CI 0.06–0.48; pNR responder HR 0.17 95% CI 0.06–0.54; mNR responder HR 0.13 95% CI 0.02–0.66). Conclusions In this study metabolic response on FDG PET-CT after neoadjuvant chemotherapy was predictive of pathological response in both the primary tumour and lymph node metastases of patients with oesophageal adenocarcinoma. Patients who had a favourable metabolic or pathological response in the primary tumour or lymph nodes had improved survival compared to non-responders. It has been suggested that commonly utilised thresholds of SUVmax are not optimal for response assessment in this patient group. This is supported by the results of the present study which suggest a reduction in SUVmax of 50% in the primary tumour was not only a better predictor of pathologic response, but also tumour recurrence and survival compared with PERCIST and MUNICON criteria. No previous studies have evaluated the ability of FDG PET-CT to predict pathologic nodal response despite recent findings suggesting it is an independent predictor of survival and evidence of a discrepancy, in some patients, who demostrate a nodal response in the absence of a response in the primary tumour. The use of FDG PET-CT in assessing response to neoadjuvant chemotherapy remains an under researched area and further evaluation is needed to establish whether it could be used to tailor individualised treatment strategies.

Gross tumor volume of adenocarcinoma of esophagogastric junction corresponding to cT and cN stages measured with computed tomography to quantitatively determine resectabiliy: A case control study.

To determine whether gross tumor volume (GTV) of adenocarcinoma of esophagogastric junction (AEG) corresponding to cT and cN stages measured on CT could help quantitatively determine resectability. 343 consecutive patients with AEG, including 279 and 64 randomly enrolled in training cohort (TC) and validation cohort (VC), respectively, underwent preoperative contrast-enhanced CT. Univariate and multivariate analyses for TC were performed to determine factors associated with resectability. Receiver operating characteristic (ROC) analyses were to determine if GTV corresponding to cT and cN stages could help determine resectability. For VC, Cohen's Kappa tests were to assess performances of the ROC models. cT stage, cN stage and GTV were independently associated with resectability of AEG with odds ratios of 4.715, 4.534 and 1.107, respectively. For differentiating resectable and unresectable AEG, ROC analyses showed that cutoff GTV of 32.77 cm3 in stage cT1-4N0-3 with an area under the ROC curve (AUC) of 0.901. Particularly, cutoffs of 27.67 and 32.77 cm3 in stages cT3 and cT4 obtained AUC values of 0.860 and 0.890, respectively; and cutoffs of 27.09, 33.32 and 37.39 cm3 in stages cN1, cN2 and cN3 obtained AUC values of 0.852, 0.821 and 0.902, respectively. In VC, Cohen's Kappa tests verified that the ROC models had good performance in distinguishing between resectable and unresectable AEG (all Cohen's K values > 0.72). GTV, cT and cN stages could be independent determinants of resectability of AEG. And GTV corresponding to cT and cN stages can help quantitatively determine resectability.

CT is unreliable in locoregional staging of early colon cancer: A nationwide registry-based study.

The option to treat early colon cancer (CC) with local resection, as well as trials investigating neoadjuvant treatment, has increased the importance of identifying early-stage disease in the workup. Most CC patients are T- and N-staged preoperatively with CT, although its reliability in staging early CC remains elusive. The aim of this study was to investigate CT-staging accuracy in early CC by evaluating pT and pN stages in patients staged as cT1-2, and cT and cN stages in patients with pT1 tumors. Retrospective population-based cohort study on data from the nationwide Swedish colorectal cancer registry on all CC patients staged as cT1-2 and all patients with pT1 undergoing surgical resection 2009-2018. CT-acquired T- and N-stages were compared with final histopathology. Factors potentially influencing accuracy were analyzed with uni- and multivariate logistic regression. Computed tomography (CT) staged 4849 patients as cT1-2, whereas 2445 (50%) were pT3 and 453 (9%) pT4. Positive predictive value of the cT1-2 stage was 40%. Of 1401 pT1 patients, 624 (45%) were staged as cT1-2, 139 (10%) as cT3, 15 (1%) as cT4 and 623 (44%) as cTx. In all, 1474 (30%) of the cT1-2 patients were pN+, whereas CT staged 1062 (72%) as cN0. A total of 771 patients were staged as cN+, whereas 403 (52%) were pN0. Overall accuracy in determining N+ was 67%, with 26% sensitivity and 88% specificity. Positive and negative predictive values in determining N+ were 48% and 73%, respectively. This nationwide population-based study shows that CT-staging carries a substantial risk of understaging locally advanced tumors as cT1-2 and pT1 tumors as cTx, in addition to poor N-staging. Thus, CT obtained T- and N-staging should not be used for deciding treatment strategies in early CC.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial

Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P= 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P= 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P= 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P= 0.063), while the recurrence pattern was similar (P= 0.802). NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.