Trimodality Therapy Research Articles

P263 Patients with Muscle-Invasive Bladder Cancer (MIBC) unfit for Radical Cystectomy (RC): Trimodal Therapy (TMT)

P263 Patients with Muscle-Invasive Bladder Cancer (MIBC) unfit for Radical Cystectomy (RC): Trimodal Therapy (TMT)

Gliosarcoma: A Multi-Institutional Analysis on Clinical Outcomes and Prognostic Factors.

This study describes oncological outcomes and investigates prognostic factors for patients with gliosarcomas (GSM). Histopathologically confirmed GSM patients who underwent treatment at five European institutions were retrospectively analyzed. We analyzed 170 patients with a median clinical follow-up time of 9.2 months. The majority received surgery (94.1%), postoperative radiotherapy (pRT, 81.8%), and temozolomide (TMZ)-based postoperative chemotherapy (66.5%). The median overall survival (OS) and progression-free survival (PFS) were 12.3 and 6.6 months, respectively. In the multivariable Cox regression analysis (MVA), the following factors were significantly associated with OS: age per year (hazard ratio (HR): 1.03, p < 0.001), subtotal resection (STR) versus biopsy only (HR: 0.15, p = 0.018), gross total resection (GTR) versus biopsy only (HR: 0.13, p = 0.011), pRT versus no pRT (HR: 0.20, p < 0.001), postoperative TMZ-based chemotherapy versus no postoperative chemotherapy (HR: 0.44, p = 0.003), MGMT promoter non-methylated versus methylated (HR: 1.79, p = 0.05), and tumor diameter per cm (HR: 1.15, p = 0.046). For PFS, the following factors were significantly associated in the MVA: GTR versus biopsy only (HR: 0.19, p = 0.026), pRT versus no pRT (HR: 0.36, p = 0.006), postoperative TMZ-based chemotherapy vs. no postoperative chemotherapy (HR: 0.39, p < 0.001), MGMT promoter status unknown versus methylated (HR: 1.69, p = 0.034), and tumor diameter per cm (HR: 1.18, p = 0.016). Sex, primary or secondary GSM, and TP53 mutational status were not significantly associated with OS or PFS. Trimodal therapy comprising surgical resection, pRT and TMZ-based chemotherapy appears to have the most beneficial effect on survival in GSM patients. Smaller tumor size, younger age and methylated MGMT promoters are associated with improved survival. To our knowledge, this is the largest multi-institutional cohort study investigating outcomes and prognostic factors for GSM.

Survival and Treatment Patterns in Stage II to III Esophageal Cancer

Existing clinical trials favor neoadjuvant chemoradiation therapy (NCRT) followed by surgery alone for locally advanced esophageal cancer (EC) and perioperative chemotherapy as the preferred modality for esophageal adenocarcinoma (EAC). However, it is unclear whether these trial findings are reflected in the patterns of care and survival outcomes among patients in the clinical setting. To investigate survival outcomes in the clinical setting among patients with EC after various treatment modalities. This retrospective cohort study examined data from the National Cancer Database maintained by the American College of Surgeons and focused on patients with clinical stage II or III EC, excluding those with gastroesophageal junction cancer, who underwent trimodality therapy (NCRT followed by esophagectomy), definitive chemoradiation therapy (DCRT), radiotherapy (RT) alone, or perioperative chemotherapy from January 2006 to December 2020. Analyses were conducted from December 2023 to August 2024. Perioperative chemotherapy, trimodality therapy, DCRT, and single-modality RT. A Cox proportional hazards regression model was used to compare overall survival (OS) between treatment groups in the entire cohort, among patients with squamous cell carcinoma or adenocarcinoma, and among those older than 65 years. Landmark survival analysis at 6 months was performed to reduce survivorship bias. The study included 57 116 patients (median age, 64 [IQR, 57-72] years; 45 410 [79.5%] male); 21 619 patients (37.9%) received trimodality therapy, 32 493 (57.1%) received DCRT, 2692 (4.7%) received single-modality RT, and 312 (0.5%) received perioperative chemotherapy. In the overall study population, 37 698 patients (66.0%) had EAC, and of the 312 patients that received perioperative chemotherapy, 283 (90.7%) had EAC. In adjusted survival analysis, perioperative chemotherapy (adjusted hazard ratio [AHR], 0.33; 95% CI, 0.28-0.39; P <.001) and trimodality therapy (AHR, 0.45; 95% CI, 0.44-0.46; P < .001) were associated with improved OS compared with DCRT. In contrast, RT alone was associated with worse outcomes compared with DCRT (AHR, 1.37; 95% CI, 1.30-1.45; P < .001). The median OS for perioperative chemotherapy of 66.2 months (95% CI, 43.1-111.9 months; P < .001) was longer compared with that for DCRT alone (18.1 months; 95% CI, 17.8-18.4 months; P < .001). Trimodality therapy was associated with a median OS of 43.9 months (95% CI, 42.8-45.5 months; P < .001), which was shorter than that for perioperative chemotherapy but improved compared with DCRT and RT alone, which was associated with a median OS of 13.5 months (95% CI, 12.8-14.0 months; P < .001). In the subgroup of patients older than 65 years, those who received perioperative chemotherapy had longer median OS (56.7 months; 95% CI, 36.4-115.2 months; P < .001) compared with those receiving other treatment modalities (eg, trimodality therapy: 40.1 months; 95% CI, 38.1-42.0 months; P < .001). Patients who received RT alone had the worst median OS (13.6 months; 95% CI, 12.8-14.4 months; P < .001). In this cohort study of patients with stage II to III EC, trimodality therapy was associated with improved OS compared with DCRT or RT alone for locally advanced EC and perioperative chemotherapy was associated with improved OS for adenocarcinoma.

Cell membrane camouflaged Cu-doped mesoporous polydopamine for combined CT/PTT/CDT synergistic treatment of breast cancer

Currently, traditional monotherapy for cancer often results in indiscriminate attacks on the body, leading to the emergence of new health problems. To confront these challenges, multimodal combination therapy has become necessary. However, how to develop new smart nanomaterials through green synthesis methods, delivering drugs while simultaneously synergizing multimodal combination therapies for tumor treatment, remains a topic of great significance. In this study, a biomimetic composite nanomaterial (RM-Cu/P) composed of mesoporous polydopamine (MPDA) as the core and red blood cell membranes (RBCMs) as the shell was synthesized as a drug carrier to deliver doxorubicin (DOX) while achieving synergistic chemotherapy, photothermal and chemodynamic therapy (CT/PTT/CDT). Herein, the nanoparticles were extensively characterized to examine their morphological characteristics, elemental composition, and drug-carrying capacity. Notably, the coating of RBCM reduced the toxicity of the RM-Cu/P@DOX nanoparticles, improved their targeting ability and prolonged their circulation time in vivo. The Cu-doped nanoparticles were capable of initiating a Fenton-like reaction to generate reactive oxygen species (ROS) for CDT, while the photothermal conversion efficiency (η) reached 45.20 % under NIR laser irradiation. Subsequently, the particles were examined by in vivo and in vitro experimental studies in cytotoxicity, cellular uptake, ROS levels, lysosomal escape, and mouse tumor model to evaluate their potential application in antitumor. Compared with monotherapy, the RM-Cu/P@DOX nanoparticles had multiple-stimulation response properties under redox, pH, and NIR, which exhibited the advantage of combined trimodal therapy, resulting in remarkable synergistic antitumor efficacy. In conclusion, this innovative platform exhibited promising applications in smart drug delivery and synergistic treatment of cancer.

Patterns of Failure After Definitive Trimodality Therapy for Muscle-Invasive Bladder Cancer

BackgroundReal-world outcomes, especially patterns of failure, are limited for patients with muscle-invasive bladder cancer (MIBC) treated with trimodality therapy (TMT). We aim to evaluate patterns of failure after TMT for MIBC in a typical heterogeneous population. MethodsIn the national Veterans Affairs database, patients with urothelial histology, MIBC (T2-4a/N0-3/M0) who underwent definitive intent TMT between 2000-2018. Successful TMT was defined as ≥ 50% definitive radiation dose and ≥ 1 cycle chemotherapy. Endpoints of any recurrence, metastatic (nonbladder) recurrence (MR), and local (bladder) recurrence (LR) evaluated in multivariable Fine-Gray models. Times to recurrence calculated from radiation start date. ResultsIn 347 patients with MIBC treated with TMT, 65% of patients were deemed ineligible for surgery while 35% were surgically eligible but elected for TMT. Median follow-up time was 77 months. Median overall survival was 32.4 months (95% CI: 28.2-36.7). 154 (44%) patients had no recurrence. 130 (37%) patients developed MR, median time 9.9 months. 117 (34%) patients developed LR, median time 8.7 months. In multivariable models, lymph node positive (LN+) disease (HR:3.31, 95% CI: 1.45-7.55, P < .01) and pretreatment hydronephrosis (HR:1.62, 95% CI:1.11-2.36, P = .01) were associated with higher rates of MR. No patient, tumor, or treatment variables were associated with LR. ConclusionsAcross a multi-institutional and heterogeneous population, TMT is an effective treatment for many real-world patients with MIBC. However, a notable proportion of patients develop MR and/or LR which emphasizes the need for post-treatment surveillance and improved treatment pathways. Identified high risk features (LN+ disease, pretreatment hydronephrosis) and other markers should be further investigated to delineate the patients at high risk of TMT failure who therefore may potentially benefit from augmented treatment, such as additional systemic therapy.

Self-Reported Management of Inflammatory Breast Cancer Among the American Society of Breast Surgeons Membership: Consensus and Opportunities.

Inflammatory breast cancer (IBC) is rare and biologically aggressive. We sought to assess diagnostic and management strategies among the American Society of Breast Surgeons (ASBrS) membership. An anonymous survey was distributed to ASBrS members from March to May 2023. The survey included questions about respondents' demographics and information related to stage III and IV IBC management. Agreement was defined as a shared response by >80% of respondents. In areas of disagreement, responses were stratified by years in practice, fellowship training, and annual IBC patient volume. The survey was administered to 2337 members with 399 (17.1%) completing all questions and defining the study cohort. Distribution of years in practice was 26.0% 0-10 years, 26.6% 11-20 years and 47.4% > 20 years. Overall, 51.2% reported surgical oncology or breast fellowship training, 69.2% maintain a breast-only practice, and 73.5% treat < 5 IBC cases/year. Agreement was identified in diagnostic imaging, trimodal therapy, and mastectomy with wide skin excision for stage III IBC. Lack of agreement was identified in surgical management of the axilla; respondents with < 10 years in practice or fellowship training were more likely to perform axillary dissection for cN0-N2 stage III IBC. Locoregional management of stage IV IBC was variable. Among ASBrS members, there is consensus in diagnostic evaluation, treatment sequencing and surgical approach to the breast in stage III IBC. Differences exist in surgical management of the cN0-2 axilla with uptake of de-escalation strategies. Clinical trials are needed to evaluate oncologic safety of de-escalation in this high-risk population.

EP.08D.14 Long-Term Prognosis of Patients Undergoing Trimodality Therapy for Locally Advanced Non-Small-Cell Lung Cancer

EP.08D.14 Long-Term Prognosis of Patients Undergoing Trimodality Therapy for Locally Advanced Non-Small-Cell Lung Cancer

The impact of age on the efficacy of radiotherapy in pleural mesothelioma patients receiving trimodality therapy: a population-based study of the SEER database

The impact of age on the efficacy of radiotherapy in pleural mesothelioma patients receiving trimodality therapy: a population-based study of the SEER database

The Role of Maximal TURBT in Muscle-Invasive Bladder Cancer: Balancing Benefits in Bladder Preservation and Beyond.

Radical cystectomy with lymph node dissection and urinary diversion is the gold-standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC). However, in patients who refuse cystectomy, or in whom cystectomy carries a high risk, bladder-preserving therapies remain potential options. Bladder preservation therapies can include maximal debulking transurethral resection of bladder tumor (TURBT), concurrent chemoradiation therapy, followed by cystoscopy to assess response. At this time, maximal TURBT is recommended for patients prior to the initiation of chemoradiation therapy or in patients with residual bladder tumors after the completion of chemoradiation therapy. That being said, TURBT carries significant risks such as bladder perforation, bleeding, and infection, ultimately risking delayed systemic treatment. Hence, understanding its role within trimodal therapy is crucial to avoid undue suffering in patients. Herein, we review the current literature on the impact of debulking TURBT in non-metastatic MIBC.

Single-Atom Iridium Nanozyme-Based Persistent Luminescence Nanoparticles for Multimodal Imaging-Guided Combination Tumor Therapy.

Persistent luminescence nanoparticles (PLNPs) can achieve autofluorescence-free afterglow imaging, while near-infrared (NIR) emission realizes deep tissue imaging. Nanozymes integrate the merits of nanomaterials and enzyme-mimicking activities with simple preparation. Here PLNPs are prepared of Zn1.2Ga1.6Ge0.2O4:Cr0.0075 with NIR emission at 700 nm. The PLNPs are then incubated with IrCl3 solution, and the nanoparticles are collected and annealed at 750 °C to obtain iridium@PLNPs. Iridium is observed on the PLNPs at the atomic level as a single-atom nanozyme with peroxidase-like catalytic activity, photothermal conversion, and computed tomography (CT) contrast capability. After coating with exosome membrane (EM), the Ir@PLNPs@EM composite exhibits long-lasting NIR luminescence, peroxidase-like catalytic activity, photothermal conversion, and CT contrast capability, with the targeting capability and biocompatibility from EM. Thus, NIR afterglow/photothermal/CT trimodal imaging-guided photothermal-chemodynamic combination therapy is realized as validated with the in vitro and in vivo inhibition of tumor growth, while toxicity and side effects are avoided as drug-free treatment. This work offers a promising avenue for advanced single-atom nanozyme@PLNPs to promote the development of nanozymes and PLNPs for clinical applications.

The Role of Frailty in the Treatment of Locally Advanced Rectal Cancer.

Owing to the gradual aging of today's population, an increase in the prevalence of frailty syndrome has been noticed. This complex state of health, characterized by decreased resilience and tolerance with concurrent increased vulnerability to stressors and adverse health-related factors, has drawn researchers' attention in recent years. Rectal cancer, which constitutes ~30% of all colorectal cancers, is a disease noticeably related to the elderly. In its locally advanced form, it is conventionally treated with trimodal therapy-neoadjuvant chemoradiotherapy followed by total mesorectal excision and adjuvant chemotherapy. Despite its good clinical outcomes and improvement in rectal cancer local control, as evidenced by clinical trials, it remains unclear if all frail patients benefit from that approach since it may be associated with adverse side effects that cannot be handled by them. As old patients, and frail ones even more noticeably, are poorly represented in the clinical trials describing outcomes of the standard treatment, this article aims to review the current knowledge on the trimodal therapy of rectal cancer with an emphasis on novel approaches to rectal cancer that can be implemented for frail patients.

Abstract C037: Inflammatory breast cancer by metastatic status: Racial and ethnic and socioeconomic disparities in receipt of treatment

Abstract Background: Inflammatory breast cancer (IBC) is a relatively rare but aggressive type of breast cancer. Racial and ethnic minority patients are disproportionately affected by IBC and often face barriers to accessing cancer care and services. However, racial and ethnic disparities in receipt of treatment are not well defined among patients with IBC by metastatic status. Methods: We analyzed data from patients with IBC in the 2004-2020 U.S. National Cancer Database. Five treatment modalities were assessed: hormone therapy, chemotherapy, radiotherapy, surgery, and trimodal therapy. Metastatic status was dichotomous as “metastatic/non-metastatic.” Racial and ethnic groups included Asian or Pacific Islander, American Indian, Alaska Native, or Other, Black, Hispanic, and White. Separate logistic regression models were fit, adjusting for sociodemographic and clinicopathological characteristics, stratified by metastatic status. Adjusted odds ratios (aOR) and 95% CIs were calculated. Results: Of 33,376 patients with IBC (mean age 58 years [SD=14]), most (70.6%) identified as White, followed by 18.1% as Black, 7.0% as Hispanic, 2.5% as Asian or Pacific Islander, 1.8% as American Indian, Alaska Native, or Other; and 32.5% were metastatic. In the non-metastatic cohort, Black (72.7%; aOR 0.79, 95% CI: 0.63-0.98) or Asian or Pacific Islander (74.8%; aOR 0.59, 95% CI: 0.38-0.90) patients had lower odds of receiving hormone therapy than White patients (78.0%). Compared with White patients, Black patients had a lower likelihood of receiving chemotherapy (89.1% vs. 89.5%; aOR 0.67, 95% CI: 0.53-0.86), surgery (78.4% vs. 85.3%; aOR 0.65, 95% CI: 0.55-0.77), or trimodal therapy (81.5% vs. 87.3%; aOR 0.61, 95% CI: 0.49-0.76). American Indian, Alaska Native, or Other (65.0%; aOR 0.64, 95% CI: 0.42-0.97) and Black (63.6%; aOR 0.71, 95% CI: 0.61-0.82) patients had lower odds of receipt of radiotherapy than White patients (70.6%). In the metastatic cohort, Black patients had a lower likelihood of receiving hormone therapy (55.2% vs. 63.5%; aOR 0.61, 95% CI: 0.48-0.78), chemotherapy (78.7% vs. 78.2%; aOR 0.75, 95% CI: 0.60-0.95), surgery (28.2% vs. 35.1%; aOR 0.68, 95% CI: 0.56-0.82), or trimodal therapy (30.4% vs. 40.4%; aOR 0.63, 95% CI: 0.48-0.82) than White patients. There were no statistically significant differences in receipt of treatment between White and other racial and ethnic patients with metastatic IBC. Furthermore, we observed significantly differential rates of treatment receipts by socioeconomic factors including median household income quartile, insurance coverage, and facility type. Conclusions: In this study of a large U.S. national IBC patient cohort, racial and ethnic minority patients were less likely than White patients to have received treatment for IBC, with Black patients being the most affected. Our findings highlight racial and ethnic disparities and socioeconomic inequities in treatment receipts, suggesting the need for oncology programs to improve equitable care access and reduce these disparities in the IBC population. Citation Format: Jincong Q. Freeman, Jared H. Hara, Olasubomi J. Omoleye. Inflammatory breast cancer by metastatic status: Racial and ethnic and socioeconomic disparities in receipt of treatment [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C037.

As Aggregation-Induced Emission Meets with Noncovalent Conformational Locks: Subtly Regulating NIR-II Molecules for Multimodal Imaging-Navigated Synergistic Therapies.

Phototheranostics is growing into a sparking frontier in disease treatment. Developing single molecular species synchronously featured by powerful absorption capacity, superior second near-infrared (NIR-II) fluorescence and prominent photothermal conversion ability is highly desirable for phototheranostics, yet remains formidably challenging. In this work, we propose a molecular design philosophy that the integration of noncovalent conformational locks (NoCLs) with aggregation-induced emission (AIE) in a single formulation is able to boost multiple photophysical properties for efficient phototheranostics. The introduction of NoCLs skeleton with conformation-locking feature in the center of molecular architecture indeed elevates the structural planarity and rigidity, which simultaneously promotes the absorption capacity and bathochromic-shifts the emission wavelength centered in NIR-II region. Meanwhile, the AIE tendency mainly originated from flexibly propeller-like geometry at the ends of molecular architecture eventually endows the molecule with satisfactory emission intensity and photothermal conversion in aggregates. Consequently, by utilizing the optimized molecule, unprecedented performance on NIR-II fluorescence-photoacoustic-photothermal trimodal imaging-guided photothermal-chemo synergistic therapy is demonstrated by the precise tumor diagnosis and complete tumor ablation.

Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review

PurposeOptimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols.MethodsA systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted.ResultsOut of 200 identified publications, 43 studies (28 retrospective, 15 prospective) were selected, encompassing 7447 patients (study sizes from 24 to 728 patients). Recurrence rates in the urinary bladder varied between 14–52%; 3–16% were muscle-invasive while 11–36% were non-muscle invasive. Nodal recurrence occurred at 13–16% and distant metastases at 15–35%. After 5 and 10 years of follow-up, around 60–85% and 45–75% of patients could preserve their bladder, respectively. Various prognostic risk factors associated with relapse and inferior survival were proposed, including higher disease stage (> c/pT2), presence of extensive/multifocal carcinoma in situ (CIS), hydronephrosis, multifocality, histological subtypes, incomplete transurethral resection of bladder tumor (TURBT) and incomplete response to radio-chemotherapy. The analyzed follow-up guidelines varied slightly in terms of the number, timing, and types of investigations, but overall, the recommendations were similar.ConclusionRandomized prospective studies should focus on evaluating the impact of specific follow-up protocols on oncological and functional outcomes following trimodal treatment for muscle-invasive bladder cancer. It is crucial to evaluate personalized adaption of follow-up protocols based on established risk factors, as there is potential for improved patient outcomes and resource allocation.

Fabrication of a novel macrophage-targeted biomimetic delivery composite hydrogel with multiple-sensitive properties for tri-modal combination therapy of rheumatoid arthritis

In this study, a porous polydopamine (PDA) nanoparticle-decorated β-glucan microcapsules (GMs) nanoplatform (PDA/GMs) were developed with macrophage-targeted biomimetic features and a carriers-within-carriers structure. Indocyanine green (ICG) and catalase (CAT) were subsequently co-encapsulated within the PDA/GMs to create a multifunctional nanotherapeutic agent, termed CIPGs. Furthermore, CIPGs and sinomenine (SIN) were co-loaded within a thermo-sensitive hydrogel to design an injectable delivery system, termed CIPG/SH, with potential for multi-modal therapy of rheumatoid arthritis (RA). Photothermal studies indicated that the CIPGs hold excellent photothermal conversion ability and thermal stability, as they combined the photothermal performance of both PDA and ICG. Meanwhile, the CIPGs displayed favorable oxygen self-supplying and photodynamic performance. The CIPGs showed near-infrared (NIR)-induced phototoxicity, effectively inhibiting macrophage proliferation and displaying remarkable antibacterial activity. In vitro drug release from the prepared CIPG/SH showed a controlled release pattern. Animal experiments conducted on an RA mice model confirmed that the formulated CIPG/SH exhibited significant therapeutic effects. By integrating the biological advantages, photothermal/photodynamic performance of the CIPGs, and controlled drug release performance of the thermo-sensitive hydrogels in a single delivery system, the prepared injectable CIPG/SH represents a novel versatile delivery system with great potential for multi-modal combination targeting therapy in RA.

Adjuvant chemoradiotherapy plus pembrolizumab for locally advanced esophageal squamous cell carcinoma with high risk of recurrence following neoadjuvant chemoradiotherapy: a single-arm phase II study

BackgroundAdjuvant nivolumab reduces recurrence in patients with locoregional esophageal cancer who had pathological residual disease after neoadjuvant chemoradiotherapy and R0 resection. However, the efficacy of adjuvant anti-PD-1 therapy in patients at higher risk of recurrence remains unclear.MethodsThis phase II trial (ClinicalTrials.gov identifier: NCT03322267) enrolled patients with locally advanced esophageal squamous cell carcinoma (ESCC) received neoadjuvant chemoradiotherapy plus esophagectomy but still had various risk factors for recurrence, such as involved or close margins (≤ 1 mm), extranodal extension of the involved lymph nodes, and the ypN2-3 stage. Patients received adjuvant therapy composed of a course of cisplatin-based chemoradiotherapy and pembrolizumab (200 mg, IV every 3 weeks) for 18 cycles. The primary endpoint was 1-year relapse-free survival (RFS) rate.ResultsTwenty-five patients were enrolled. The risk factors were tumor margins of ≤ 1 mm (18 patients), extranodal extension of the involved lymph nodes (9 patients), and the ypN2-3 stage (9 patients). The median follow-up duration was 21.6 months (95% CI: 18.7–33.2). The rate of 1-year RFS was 60.0%. The median duration of RFS and overall survival was 14.3 (95% CI: 9.0–19.5) and 21.6 (95% CI: 0.0–45.5) months, respectively. Treatment-emergent adverse events of any grade and those of ≥ 3 grade occurred in 56% and 8% of all patients receiving cisplatin-based chemoradiotherapy and in 79.2% and 12.5% of those receiving pembrolizumab.ConclusionsAdjuvant chemoradiotherapy followed by pembrolizumab is feasible and may be associated with improved 1-year RFS rate in patients at high risk of recurrence after trimodality therapy for locally advanced ESCC.Trial registration number ClinicalTrials.gov (No. NCT03322267).

Bladder-Preserving Trimodality Treatment for High-Grade T1 Bladder Cancer: Results From Phase II Protocol NRG Oncology/RTOG 0926.

To investigate the use of radiation with radiosensitizing chemotherapy following repeated transurethral resection (trimodality therapy) as an alternative to radical cystectomy in T1 bladder cancer which has failed Bacillus Calmette-Guerin (BCG). Patients with recurrent T1 bladders who had failed BCG and were recommended to undergo cystectomy were treated with trimodality therapy. The primary end point was 3-year freedom from cystectomy. Secondary end points were distant metastasis at 3 and 5 years, local recurrence, disease-specific and overall survival (OS), and safety. This single-arm phase II study enrolled 37 patients. Efficacy and safety were evaluated in 34 patients after three exclusions. The median follow-up was 5.1 years. The 3-year freedom from cystectomy rate was 88% (lower one-sided 97.5% confidence limit [CI], 72%), meeting the primary study goal. OS at 3 and 5 years was 69% (95% CI, 54 to 85) and 56% (95% CI, 39 to 74), respectively. The distant metastasis rates at 3 and 5 years were 12% (95% CI, 4 to 26) and 19% (95% CI, 7 to 34), respectively. Eight patients died due to urothelial cancer, 12 exhibited local recurrence at 3 years (cumulative incidence: 32%; 95% CI, 17 to 48), 18 experienced grade 3 adverse events, mostly hematological, and one developed grade 4 neutropenia. Trimodality therapy is an effective potential alternative to radical cystectomy for recurrent high-grade T1 urothelial cancer of the bladder. At 3 years, 88% of the patients remained free of cystectomy.

Bladder sparing options for muscle-invasive bladder cancer.

This review critically evaluates the current state of bladder-sparing options in muscle-invasive bladder cancer (MIBC) and provides an overview of future directions in the field. Bladder-sparing treatments have emerged as viable alternatives to radical cystectomy (RC) for selected patients with MIBC, especially in those who are unfit for RC or elect bladder preservation. Numerous studies have assessed the efficacy of trimodal therapy (TMT), with outcomes comparable to RC in a subgroup of well selected patients. Combining immunotherapy with conventional treatments in bladder-sparing approaches can yield promising outcomes. Current research is making significant progress in optimizing treatment protocols by exploring new combinations of systemic therapy agents, innovative drug delivery methods, and biomarker-based approaches. Furthermore, clinical markers of response are being tested to ensure adequate response assessment. Bladder preservation promise to offer a viable alternative to RC for selected patients with MIBC with the potential to improve patient quality of life. Careful patient selection and ongoing research are essential to optimize patient selection, response assessment, and salvage strategies. As evidence continues to evolve, the role of bladder preservation in MIBC is likely to expand, providing patients with more treatment options tailored to their needs and preferences.

763. TEXTBOOK ONCOLOGIC OUTCOME FOLLOWING TRIMODALITY THERAPY FOR ESOPHAGEAL ADENOCARCINOMA

Abstract Background Although the concept of textbook oncologic outcome (TOO) as an emerging quality benchmark has been validated in the general surgical oncology literature, data regarding the frequency of achieving TOO and its impact on subsequent survival outcomes in patients with esophageal adenocarcinoma (EAC) who undergo trimodality therapy remain undefined. Methods Patients with adenocarcinoma of the esophagus/gastroesophageal junction (GEJ, Siewert I/II) who underwent neoadjuvant chemoradiation and esophagectomy at a single institution (2000-2022) were retrospectively identified. Patients undergoing salvage resection were excluded. TOO was defined according to a published consensus definition: length of stay (LOS) ≤14 days, R0, ≥20 resected lymph nodes, no anastomotic leak (any grade), no Clavien-Dindo (CD) grade ≥3 complications, no hospital or intensive care unit (ICU) readmission, and no reoperation. Multivariable logistic regression was used to identify clinicopathologic features associated with TOO. Multivariable Cox regression and landmark analyses were used to quantify the association between TOO and OS. Results Of 1138 patients, TOO was observed in 38.2% (435): 90.9% (1034) R0, 60.9% (693) ≥20 lymph nodes, 89.9% (1023) no anastomotic leak, and 98.4% (1120) no in-hospital mortality. Features independently associated with reduced odds of TOO included: cervical anastomosis (OR 0.50, P=0.001), preoperative delay ≥90 days after neoadjuvant therapy (OR 0.62, P=0.004), induction chemotherapy (OR 0.74, P=0.039), coronary artery disease (OR 0.67, P=0.043). Among patients who underwent esophagectomy &amp;lt;90 days after neoadjuvant therapy and survived ≥30 days, TOO was independently associated with improved OS (HR 0.80, P=0.018). TOO remained associated with improved OS using 90-day (P=0.014) and 120-day (P=0.037) landmarks. Conclusions Although TOO is difficult to achieve following trimodality therapy for EAC, it is strongly associated with improved long-term overall survival. As such, further efforts are warranted to explore the utility of TOO as a quality benchmark in EAC patients and to validate its impact across varying practice settings.

236. THE ROLE OF ADJUVANT THERAPY FOLLOWING NEOADJUVANT CHEMORADIOTHERAPY AND ESOPHAGECTOMY IN ESOPHAGEAL CANCER

Abstract Background The objective of this study was to assess the role of adjuvant therapy following neoadjuvant chemoradiotherapy and esophagectomy in esophageal squamous cell carcinoma (ESCC). Methods We conducted a retrospective analysis involving 506 ESCC patients who underwent trimodal therapy. The clinical significance of adjuvant therapy on overall survival and disease-free survival was evaluated using Kaplan–Meier curves with log-rank tests, the Cox regression model, and a forest plot displaying hazard ratios (HR) with 95% confidence intervals. Results Among the 506 patients who had clinically positive lymph nodes and no metastasis after neoadjuvant chemoradiotherapy and esophagectomy, those who received adjuvant therapy exhibited shorter post-resection overall survival (OS) and disease-free survival (DFS), with a statistically significant difference between the two groups (Log-Rank, OS: P = 0.002; DFS: P &amp;lt; 0.001). Adjuvant therapy was not identified as an independent prognostic factor for OS (HR: 1.249; 95% CI: 0.869-1.796; P = 0.230), but it was a significantly unfavorable independent prognostic factor for DFS (HR: 1.868; 95% CI: 0.349-2.586; P &amp;lt; 0.001). Conclusion Adjuvant therapy is associated with poorer overall survival (OS) and disease-free survival (DFS) outcomes in ESCC patients with ypTNM stage I and II on final pathology following neoadjuvant chemoradiotherapy and esophagectomy. However, there was no significant difference observed in patients with ypTNM stage III or IV. Therefore, it is not recommended to undergo postoperative adjuvant therapy for patients with ypTNM stage I and II ESCC. However, for patients with ypTNM stage III and IV ESCC, further research is needed to explore adjuvant treatment strategies.