Clinical Stage T2 Research Articles

Added Value of Systemic Inflammation Markers in Predicting Clinical Stage T1 Renal Cell Carcinoma Pathologically Upstaged to T3a.

ObjectivesWe aimed to determine preoperative risk factors associated with pathologic T3a (pT3a) upstaging of clinical T1 (cT1) renal cell carcinomas (RCCs) and develop a novel model capable of accurately identifying those patients at high risk of harboring occult pT3a characteristics.MethodsA retrospective analysis of 1324 cT1 RCC patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) was performed. The study cohort was divided into training and testing datasets in a 70:30 ratio for further analysis. Univariable and multivariable logistic regression analyses were performed to identify predictors associated with cT1 to pT3a upstaging and subsequently, those significant risk factors were used to construct models. We used the area under the curve (AUC) to determine the model with the highest discrimination power. Decision curve analyses (DCAs) were applied to evaluate clinical net benefit associated with using the predictive models.ResultsThe rates of upstaging were 6.1% (n = 81), 5.8% (n = 54) and 6.8% (n = 27) in the total population, training cohort and validation cohort, respectively. Tumor size, clinical T stage, R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior) nephrometry score, lymphocyte to monocyte ratio (LMR), prognostic nutrition index (PNI) and albumin to globulin ratio (AGR) were significantly associated with pT3a upstaging. The model that consisted of R.E.N.A.L. score, LMR, AGR and PNI achieved the highest AUC of 0.70 in the validation cohort and yielded the highest net benefit. In the subpopulation with complete serum lipid profile, the inclusion of low-density lipoprotein cholesterol (LDL-C) and Castelli risk index-I (CRI-I) significantly improved the discrimination of model (AUC = 0.86).ConclusionsOur finding highlights the importance of systemic inflammation response markers and serum lipid parameters in predicting pT3a upstaging. Our model had relatively good discrimination in predicting occult pT3a disease among patients with cT1 renal lesions, and the use of the model may be greatly beneficial to urologists in risk stratification and management decisions.

Enhanced pathologic tumor response with two cycles of neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV-negative head and neck squamous cell carcinoma (HNSCC).

6008 Background: We reported that one cycle of neoadjuvant pembrolizumab induced pathologic tumor response in >10% (pTR-any) and in >50% (pTR-2) of the resection bed in 44% and 22% of patients (pts) with surgically resectable HPV-negative, Stage III/IV HNSCC ( Clin Cancer Res 2020). We hypothesized that two cycles of neoadjuvant pembrolizumab would induce pTR-2 in 50% of pts. Increasing the pathologic response rate may favorably impact clinical outcomes. Methods: Multi-institutional phase 2 trial where pts with locally advanced, HPV-negative HNSCC received two cycles of pembrolizumab (200 mg), given 42 and 21 days prior to surgery. Resected tumor was analyzed by two independent pathologists for pTR (tumor necrosis and/or giant cell/histiocytic reaction to keratinous debris) in the resection bed (primary tumor and/or lymph nodes). Additional definitions: pTR-1 (>10-49%) and major pathologic response ( > 90%). The primary endpoint was pTR-2. A sample size of 26 pts was needed to detect a significantly higher pTR-2 rate of 50%, with 80% power using a one-sided alpha level of 0.05. Pts were followed for serious adverse events (AEs) for 30 days after surgery and for AEs of clinical interest for 90 days following the last dose of pembrolizumab. Pts underwent baseline blood collection and tumor biopsies to match with blood and surgical specimens obtained post-pembrolizumab. Planned correlatives included PD-L1 expression, immune function, and molecular signatures of activation in the pre- and post-treatment blood and tumor tissue. Results: Characteristics of 29 enrolled and treated pts were median age 62 (30-82) yrs, smoking history 62% (18 pts); clinical stage T2 (n = 6), T3 (n = 5), T4 (n = 18) and N0/1 (n = 17), N2 (n = 12). All treated patients received two cycles of neoadjuvant pembrolizumab, which was tolerated well with only one (3%) grade 3 AE (rash) and no grade 4 AEs. The primary endpoint was evaluable in 25 pts, and not evaluable in 4 pts (one pt withdrew before surgery and in three pts, pTR review was pending). pTR-2 occurred in 44% (11 of 25 pts), and 4 (16%) of these pts had a major pathologic response including 1 (4%) pathologic CR at the primary site. Conclusions: Two (vs one) cycles of neoadjuvant pembrolizumab resulted in a two-fold increase in the frequency of pTR-2 (44% vs 22%). These data imply that the frequency of pTR to neoadjuvant pembrolizumab can be improved by increasing the number of cycles and the treatment interval. Clinical trial information: NCT02296684.

Survival outcomes of breast cancer patients with brain metastases: Single center experience from Northern India.

e13003 Background: Brain metastasis (BM) is a poor prognostic factor for survival among breast cancer (BC) patients. Very few studies reported in the literature have challenged this premise, suggesting that time to the occurrence of brain metastasis and the survival times following brain metastasis differ significantly between BC subtypes. The purpose of this study was to evaluate the clinico-pathological characteristics associated with brain metastasis free survival (BMFS), survival after brain metastases (SABM) and overall survival among Indian women with BC and BM. Methods: Among 621 patients treated for metastatic BC from 2015 to 2018 at All India Institute of Medical Sciences-New Delhi, 79 (12.7%) patients were identified to have BM. Of these ten individuals have presented with BM at the time of presentation. Survival analysis and Cox proportional hazards models were fitted to explore clinco-pathological factors that are associated with survival outcomes in these individuals. Results: Median age of the sample is 42 years (range:22-64). Triple negative breast cancers (TNBC) accounted for 25.3% and HER2 positive were 49.4% in our sample. Median time for the occurrence of BM from cancer diagnosis was 20.5 months (95% CI:14.7-26.2) in the overall sample, while among TNBC and HER2 positive tumors was 14.1 and 20.6 months respectively. In Cox multivariable model, T4stage [Hazard Ratio (HR) (95%CI): 2.4(1.1-5.3)], having a metastatic disease other than to brain at the time of presentation [HR(95%CI): 2.8(1.5-5.4)] and TNBC [HR(95%CI): 2.7(1.1-6.7)], was observed to be significantly associated with BMFS. Median SABM was 7.9 months (95% CI 5.2–16.2) and the median overall survival from the cancer diagnosis was 32.4 months (95% CI 23.4–40.8). Adjusted for age, only the presence of multiple brain lesions (>2) was significantly associated with SABM [HR (95%CI): 2.4(1.1-5.2)]. However, TNBC [HR (95%CI): 2.9(1.2-7.4)]and baseline metastatic disease [HR (95%CI): 2.2(1.2-4.2)] were significantly associated with overall survival following cancer diagnosis in these individuals. HER2 positivity was not associated with BMFS or SABM in this cohort. Conclusions: In this single-institutional study, clinical T4 stage, TNBC subtype and baseline metastatic disease have shown to be significantly associated with BMFS and overall survival. These results suggest that women in Indian population with these baseline clinico-pathological characteristics at the diagnosis of breast of cancer should be frequently monitored for BM.

The national impact of the COVID-19 pandemic on U.S. prostate cancer community care.

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]

Use of brain radiotherapy as part of first course of treatment for NSCLC with de novo brain metastasis.

9118 Background: Loco-regional management of brain metastases from non-small cell lung cancer (NSCLC) are surgery and/or brain radiotherapy, either whole brain (WBRT) or stereotactic (SRS). We used a national registry to evaluate trends in the use of brain radiotherapy as part of the first course of management in patients diagnosed with de novo brain metastasis. Methods: We retrospectively analyzed the National Cancer Database (NCDB) to identify patients with NSCLC and de novo brain metastasis diagnosed from 2004-2016. We described the socio-demographic and clinical characteristics of this population, then used chi-squared testing to evaluate for an association between these variables and the use of brain radiotherapy (either SRS or WBRT). Significant variables (p < 0.05) were included in a multiple logistic regression model. Results: Of n = 41,454 patients with NSCLC and de novo brain metastasis, n = 27,949 (67.4%) received either SRS or WBRT as part of their first course of treatment, while n = 13,505 (32.6%) did not receive primary brain radiation. Of those that did not receive radiation: n = 9,927 (73.5%) were < 70 years old while n = 3,578 (26.5%) were ≥70. N = 11,081 (82.7%) were White, n = 1,550 (11.6%) were Black and n = 768 (5.7%) were Asian. Variables significantly associated with the use of primary brain radiotherapy at the multivariate level were: treatment facility type (p = 0.004), tumor histology (p < 0.001), clinical T-staging (p < 0.001), and clinical N-staging (p < 0.001). Age, sex, race, comorbidity, grade, insurance status, and setting (metro vs. rural vs. urban) were not significantly associated with the use of radiotherapy. Compared to patients treated at community cancer programs (CPs), those treated at comprehensive community CPs (OR 1.152, 95% CI 1.027-1.291, p = 0.015) and academic CPs (OR 1.242, 95% CI 1.104-1.398, p < 0.001) were more likely to receive primary brain radiotherapy. Patients with squamous NSCLC were less likely (OR 0.680, 95% CI 0.619-0.747, p < 0.001) to receive brain radiotherapy compared to those with adenocarcinoma. Finally, patients with advanced T-staging (p < 0.001) and N-staging (p < 0.001) were less likely (OR < 1) to receive brain radiotherapy as part of the first course of treatment. Conclusions: While insurance status and setting were not significantly associated with the use of brain radiotherapy, facility type was. Further research is needed to evaluate whether this is a true disparity in medical practice, or the differences can be explained by characteristics of the patient population undocumented by the NCDB (e.g. severity of brain metastasis). Additionally, patients with larger primary tumors were less likely to receive brain radiation as part of the first course of treatment, which may reflect the need for local therapy prior to treating metastatic sites.

Pathologic upstaging in resected pancreatic adenocarcinoma: Risk factors and impact on survival.

Clinical and pathologic staging determine treatment of pancreatic cancer. Clinical stage has been shown to underestimate final pathologic stage in pancreatic cancer, resulting in upstaging. National Cancer Database was used to identify clinical stage I pancreatic adenocarcinoma. Univariate, multivariable logistic regression, and Cox proportional hazard ratio were used to determine differences between upstaged and stage concordant patients. Upstaging was seen in 80.2% of patients. Factors found to be significantly associated with upstaging included pancreatic head tumors (OR2.56), high-grade histology (OR1.74), elevated Ca 19-9 (OR2.09), and clinical stage T2 (OR1.99). Upstaging was associated with a 45% increased risk of mortality compared to stage concordant disease (HR1.44, p < .001). A majority of clinical stage I pancreatic cancer is upstaged after resection. Factors including tumor location, grade, Ca 19-9, and tumor size can help identify those at high risk for upstaging.

Risk factors for local recurrence and long term survival after minimally invasive intersphincteric resection for very low rectal cancer: Multivariate analysis in 161 patients

IntroductionIntersphincteric resection (ISR) is the ultimate anal-sparing technique as an alternative to abdominoperineal resection in selected patients. Oncological safety is still debated. This study analyses long-term oncological results and evaluates risk factors for local recurrence (LR) and overall survival (OS) after minimally-invasive ISR. Materials and methodsRetrospective single-center data were collected from a prospectively maintained colorectal database. A total of 161 patients underwent ISR between 2008 and 2018. OS and local recurrence-free survival (LRFS) were assessed using Kaplan-Meier analysis (log-rank test). Risk factors for OS and LRFS were assessed with Cox-regression analysis. ResultsMedian follow-up was 55 months. LR occurred in 18 patients. OS and LRFS rates at 1, 3, and 5 years were 96%, 91%, and 80% and 96%, 89%, and 87%, respectively. Tumor size (p = 0.035) and clinical T-stage (p = 0.029) were risk factors for LRFS on univariate analysis. On multivariate analysis, tumor size (HR 2.546 (95% CI: 0.976–6.637); p = 0.056) and clinical T-stage (HR 3.296 (95% CI: 0.941–11.549); p = 0.062) were not significant. Preoperative CEA (p < 0.001), pathological T-stage (p = 0.033), pathological N-stage (p = 0.016) and adjuvant treatment (p = 0.008) were prognostic factors for OS on univariate analysis. Preoperative CEA (HR 4.453 (95% CI: 2.015–9.838); p < 0.001) was a prognostic factor on multivariate analysis. ConclusionsThis study confirms the oncological safety of minimally-invasive ISR for locally advanced low-lying rectal tumors when performed in experienced centers. Despite not a risk factor for LR, tumor size and, locally advanced T-stage with anterior involvement should be carefully evaluated for optimal surgical strategy. Preoperative CEA is a prognostic factor for OS.

Abstract S02-02: The impact of resuming the breast cancer screening program in the Netherlands on breast cancer incidence and stage after its discontinuation due to the COVID-19 pandemic

Abstract Introduction: The burden of the COVID-19 pandemic forced the Dutch health care services to discontinue their national screening programs on 16 March 2020 (week 12). For breast cancer, the program invites women aged 50–74 years for biennial screening mammography. From mid-June 2020 (week 25) the breast cancer screening program was resumed, albeit with reduced capacity (max 60%). We aimed to investigate the impact of resuming the screening program on incidence, tumor-, and T-stage of screen- and non-screen-detected ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) in the Netherlands. Methods: Women, 50-74 years of age, diagnosed with DCIS or IBC in weeks 2–35 of 2018, 2019 and 2020 were selected from the Netherlands Cancer Registry. Weekly incidence of screen- and non-screen-detected tumors was calculated and expressed per 1 million women aged 50-74 years living in the Netherlands. Weeks 2-35 were divided in seven periods, representing separate phases of the pandemic. For each period, incidence of screen- and non-screen-detected tumors was stratified by clinical tumor stage (TNM) and clinical T-stage. Incidence in each period of 2020 was compared with the incidence in the same period of 2018/2019 (averaged). Results: In weeks 2-35, 7,250 patients were diagnosed in 2018, 7,299 in 2019, and 5,300 in 2020. During weeks 2-12 2020 the weekly average incidence of screen-detected tumors was 42/1 million women aged 50-74. In week 13 incidence dropped to 19, and was almost zero during weeks 14-25. Incidence increased to 4 in week 26, when the screening was gradually restarted, and increased to an weekly average of 24 tumors/1 million in weeks 30-35, when screening had restarted in most of the Netherlands. During weeks 14-16, 17-25, 26-29, and 30-35 2020 incidence of screen-detected DCIS, stage I-II tumors and T0-2 tumors was lower than in the same period of 2018/2019. Distribution of tumor- and T-stage in newly diagnosed tumors did not differ between the periods (24% DCIS, 57% stage I, 18% stage II, 1% stage III, 1% stage IV; 24% T0, 59% T1, 15% T2, 2% T3, 0% T4). During weeks 2-11 2020 the weekly average incidence of non-screen-detected tumors was 38/1 million women aged 50-74. Incidence dropped to 16 in week 14, and increased to an average of 37 tumors per week in weeks 17-35. During weeks 17-25, 26-29, and 30-35 the incidence and distribution of non-screen-detected DCIS, stage I-IV and T0-4 tumors was comparable with 2018/2019 (weekly incidence (distribution): 3 DCIS (9%), 15 stage I (40%), 13 stage II (36%), 3 stage III (7%), 3 stage IV (8%); 3 T0 (9%), 17 T1 (45%), 12 T2 (34%), 3 T3 (8%), 2 T4 (5%)). Conclusion: The temporary suspension of the breast cancer screening program reduced the incidence of breast cancer. After resuming screening the incidence did not raise above the incidence in 2018/2019, therefore it is expected that the incidence will rise during the next months. The results to date did not show a shift towards a higher tumor stage or T-stage. Citation Format: Anouk H. Eijkelboom, Linda de Munck, Marc B.I. Lobbes, Jelle Wesseling, Carla H. van Gils, Pieter J. Westenend, Cristina Guerrero Paez, Ruud M. Pijnappel, Helena M. Verkooijen, Mireille J.M. Broeders, Sabine Siesling. The impact of resuming the breast cancer screening program in the Netherlands on breast cancer incidence and stage after its discontinuation due to the COVID-19 pandemic [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S02-02.

Effect of optimal neoadjuvant chemotherapy on oncological outcomes of locally advanced bladder cancer with laparoscopic radical cystectomy: A matched‐pair analysis in a multicenter cohort

To assess the effect of optimal neoadjuvant chemotherapy of at least three cycles of cisplatin-based regimen on oncological outcomes of clinical stageT3 or higher bladder cancer treated with laparoscopic radical cystectomy. Laparoscopic radical cystectomies carried out at 10 institutions were included in this retrospective study. The outcomes of patients who received optimal neoadjuvant chemotherapy and those who did not receive neoadjuvant chemotherapy were compared using propensity score matching in clinical stageT3-4 or T2 cohorts, separately. Of the 455 patients screened, matched pairs of 54 patients in the clinical T3-4 cohort and 68 patients in the clinical T2 cohort were finally analyzed. In the cT3-4 cohort, the 5-year overall survival (78% vs 41%; P=0.014), cancer-specific survival (81% vs 44%; P=0.008) and recurrence-free survival (71% vs 53%; P=0.049) were significantly higher in the optimal neoadjuvant chemotherapy group than in the no neoadjuvant chemotherapy group; no significant survival difference was shown between the two groups in the cT2 cohort. In the cT3-4 cohort, the incidence of local recurrence (4% vs 26%; P=0.025) and abdominal or intrapelvic recurrence, including peritoneal carcinomatosis (7% vs 30%; P=0.038), was significantly lower in the optimal neoadjuvant chemotherapy group. Administration of optimal neoadjuvant chemotherapy has a significant survival benefit. It decreases the incidence of local and atypical recurrence patterns in patients with clinical stageT3 or higher locally advanced bladder cancer undergoing laparoscopic radical cystectomy.

Can normalized carcinoembryonic antigen following neoadjuvant chemoradiation predict tumour recurrence after curative resection for locally advanced rectal cancer?

The aim of this work was to evaluate whether normalized carcinoembryonic antigen (CEA) following neoadjuvant chemoradiation predicts the prognosis following curative resection in locally advanced rectal cancer. Patients who underwent neoadjuvant chemoradiation and curative resection for locally advanced rectal cancer between 2010 and 2015 were divided into three groups: Group A (n=119, normal-to-normal): normal CEA before and after neoadjuvant chemoradiation; Group B (n=37, high-to-normal): elevated CEA before and normal CEA after neoadjuvant chemoradiation; Group C (n=36, high-to-high): elevated CEA before and after neoadjuvant chemoradiation. Overall and disease-free survival were compared. Univariate and multivariate analyses identified potential predictors for recurrence. One hundred and ninety two patients [median age 59 years (range 31-87), 65.1% male] were identified: 54.7% had low rectal cancer: 12.5% were clinical stage T4 and 70.3% were clinically node positive; 21.9% achieved complete pathological response; 24.5% had abdominoperineal resection (APR); and 70.3% underwent adjuvant chemotherapy following curative resection. Significantly more patients in Group C underwent APR (p=0.0209), had advanced pathological T stage (P=0.0065) and a higher prevalence of perineural invasion (p=0.0042). Overall and disease-free survival were significantly higher for Group A than for Group C [hazard ratio (HR)=4.32, 95% CI=1.66-11.21, p=0.0026 and HR=2.68, 95% CI=1.33-5.40, p=0.0057, respectively]. No significant difference was noted between Groups A and B for overall (p=0.0591) or disease-free (p=0.2834) survival. Another risk factor associated with recurrence and death was clinical T4 stage; nodal positivity was a risk factor only for recurrence. Elevated CEA after neoadjuvant chemoradiation and clinical stage T4 disease were unfavourable predictors for overall and disease-free survival. Normalized CEA during neoadjuvant chemoradiation may serve as a prognosticator, although pretreatment CEA may significantly affect survival.

CRBP-TS - evaluation of a home-based training and health care program for colorectal, breast, and prostate cancer using telemonitoring and self-management: study protocol for a randomized controlled trial

BackgroundPhysical training is recommended in various national and international guidelines for patients with cancer. Observational studies have shown that physical activity leads to reduced recurrence and mortality rates by 20–40% in colorectal, breast, and prostate cancer. Despite existing evidence, a systematic care structure is still lacking. The primary aim of this study is to implement and evaluate an online training platform to strengthen physical performance and patient empowerment after cancer surgery.MethodsThe evaluation will be conducted as a prospective multicenter randomized controlled trial with three subgroups (colorectal-, breast-, and prostate cancer). Each group will include 100 patients (total 300 patients including dropouts; clinical stages T1–3 and/or N+; M0 after surgery intervention) and the primary endpoint (13% increase in the maximal oxygen consumption during exercise) will be examined. The intervention group will receive a 6-month home-based online training (2–3 times per week strength-endurance training using video presentations), bidirectional activity feedback information, online communication, and online counseling. The control group (usual care) will be advised lifestyle improvement. In-hospital testing will be performed before, during, and after the intervention. In addition to cardiopulmonary capacity, tumor specific diagnostics (liquid biopsy, depression and fatigue assessment, metabolic and endothelial screening) will be applied.DiscussionDue to the increasing incidence of cancer, associated with considerable mortality, morbidity and impaired quality of life, there is an imperative requirement for improved cancer care, of which structured physical training may become an integral component.Trial registrationDRKS-ID: DRKS00020499; Registered 17 March 2020.

Is Neoadjuvant Treatment Justified in Clinical T1 Pancreatic Ductal Adenocarcinoma?

Introduction: Studies on neoadjuvant treatment have been actively conducted in patients with resectable pancreatic cancer. However, neoadjuvant treatment effectiveness, especially in clinical T1 stage patients, still needs to be determined. We comparatively evaluated the oncologic benefit of preoperative neoadjuvant treatment in clinical T1 stage pancreatic cancer. Methods: Data from two centers were included in the comparative analysis, with overall and recurrence-free survival as primary outcomes, between January 2010 and December 2017. Results: In total, 45 patients were retrospectively reviewed in this study. Two patients in the neoadjuvant group were excluded because of distant metastasis during neoadjuvant treatment. Finally, 43 patients underwent a pancreatectomy for clinical T1 pancreatic cancer, of whom, 35 and 8 patients underwent upfront surgery and neoadjuvant treatment, respectively. Overall survival was similar in the two study groups (5-year overall survival rate: neoadjuvant group, 75%; upfront surgery group, 43.9%, p = 0.066). Conclusions: In our study on patients with clinical T1 stage pancreatic cancer, no significant differences were reported in the oncological outcome in the neoadjuvant therapy group. Large-scale prospective studies are needed to determine the survival benefits of neoadjuvant treatment for early-stage pancreatic cancer.

The effect of maximum tumor diameter on disease control in intermediate and high-risk prostate cancer patients treated with brachytherapy boost.

252 Background: Larger maximum tumor diameter (MTD) has been associated with worse prostate cancer outcomes for those undergoing surgery as well as salvage radiation. MTD is also an important consideration for patients weighing active surveillance. However, the impact of MTD in intermediate and high-risk prostate cancer treated with external beam radiotherapy (EBRT) and brachytherapy boost is unknown. We set out to evaluate MTD of the dominant nodule on MRI as a prognostic factor in patients treated with EBRT and brachytherapy boost for localized prostate cancer. Methods: Patients with prostate cancer treated with EBRT and brachytherapy boost were identified from an institutional database. In patients with a pretreatment MRI, data on MTD were retrospectively collected. Clinical data including age, ADT use, pretreatment PSA, International Society of Urologic Pathology (ISUP) group, clinical T-stage, and presence of adverse pathology on imaging (either seminal vesicle invasion or extraprostatic extension) were also collected. Multivariable and univariable cox proportional hazards models for biochemical failure (BF) and distant metastasis (DM) were produced in patients with MTD grouped by receiver operating characteristic (ROC) cutpoint. Cumulative hazard functions for BF and DM were compared with log-rank test and stratified by ISUP group. Results: Of 191 patients treated with EBRT and brachytherapy boost, 113 had pretreatment MRI and available MTD measurement. Median follow up was 40 months (interquartile range 23-66 months) and median MTD was 17 mm (interquartile range 13-22mm). Increasing MTD was associated with higher T stage and increased ADT use. ROC cutpoint optimization identified MTD of 24mm to be the optimal cut-point for both BF and DM. On univariate log-rank analysis, patients with MTD &gt; 24mm had higher 5-year BF (31% vs 4%, p = 0.004) and DM (21% vs 4%, p = 0.002) than those with MTD≤24. Stepwise multivariable cox model for BF (P = 0.130, HR 1.08, 95% CI 0.98-1.21) and DM (P = 0.115, HR 1.09, 95% CI 0.98-1.23), MTD did not demonstrate statistical significance when controlling for clinical t-stage, adverse pathologic features on imaging, ISUP group, and ADT use. However, in patients with ISUP group 4-5 disease, MTD &gt; 24 was independently associated with increased risk of DM (P = 0.032, HR 1.18, 95% CI 1.01-1.37). Conclusions: This is the first study to evaluate MTD on MRI as a prognostic factor in the setting of brachytherapy boost. These results demonstrate that for patients treated with EBRT and brachytherapy boost, MTD is independently associated with risk for metastasis in patients with ISUP grade 4 and 5 disease. Although these results require further validation, this suggests a possible role for MTD as a factor in risk assessment models and clinical decision-making.

Temporal trends and predictors in diagnosing pathologic node-positive prostate cancer in clinically node-negative patients.

128 Background: The management of men with pathologically node positive (pN+) prostate cancer (PCa) is controversial. Here, we describe the temporal patterns and predictors of incidental pN+ PCa men with clinically node negative (cN0) PCa. Methods: We performed a retrospective analysis of men with nonmetastatic, cN0, PCa from the National Cancer Database from 2010 to 2017. Clinical factors included in analysis were pretreatment PSA, pre-surgical International Society of Urological Pathology (ISUP) grade group (GG), clinical T-stage, margin status, and number of nodes sampled. Patient demographic factors included in analysis were age, comorbidity index, race, insurance status, and treatment facility type. We performed univariable and multivariable logistic regression to evaluate temporal trends in the rates of cN0,pN+ prostate cancer diagnosed over time. Two-level hierarchical logistic regression was used to identify covariates associated with pN+ disease. Patients were clustered within treatment facilities to account for individual facility practice patterns. Results: We identified 304,234 men with cN0 PCa who underwent radical prostatectomy (RP) between 2010 and 2017. Within this group 10,919 (3.59%) were found to have pN+ disease. During this period, the annual rate of pN+ PCa increased from 2.02% (n=822) in 2010 to 5.12% (n=2,072) in 2017 (p&lt;0.001). On multivariable logistic regression, ISUP GG was most strongly associated with detection of pN+ PCa. Compared to ISUP GG1, GG2 (OR 3.5, p &lt;0.001), GG3 (OR 8.8, p &lt;0.001), GG4 (OR 12.6, p &lt;0.001) and GG 5 (OR 26.5, p &lt;0.001 ) were all significantly associated with pN+ PCa. Over the study period, the rates of pN+ identification increased from 5.5% to 9.4% in men with GG4, and from 13.4% to 19.5% in men with GG5 (p &lt;0.001). Between 2010 and 2017, the rates of RP in GG4 and GG5 similarly increased by 12% and 16%, respectively (p &lt;0.001). Other significant covariates are depicted in Table. 22% of the total variance was explained by inter-facility variation. Conclusions: The proportion of men with cN0 found to have pN+ PCa is increasing over time, with pN+ incidentally found in nearly 1 in 10 men with GG4 and 1 in 5 men with GG5 PCa. GG4 and GG5 are the strongest independent predictors of pN+ disease, while controlling for clinical and demographic factors. As incidental pN+ results in upstaging, often requiring adjuvant treatment with radiation and systemic therapies, these data are useful for informing discussions prior to RP. [Table: see text]

Patterns of care and treatment outcomes in locoregional squamous cell carcinoma of the prostate.

260 Background: Primary pure prostate squamous cell carcinoma (PSCC) is a rare, aggressive disease accounting for less than 0.5-1% of prostate cancer diagnoses. PSCC is a distinct entity from adenocarcinoma with historically poor outcomes, often presenting in younger patients with lower urinary tract symptoms and normal PSA. There are currently no established treatment guidelines. Case reports are limited but describe multiple treatment approaches including various combinations of surgery, platinum and non-platinum-based chemotherapy, radiotherapy and androgen deprivation therapy, with selected reports showing longer survival times with a combined modality approach. Methods: Seeking to identify practice patterns and treatment outcomes, we performed a retrospective analysis of the United States National Cancer Database to identify 66 males with locoregional, nonmetastatic primary pure squamous cell carcinoma of the prostate and treated with surgery, chemotherapy, and/or radiotherapy between 2004 and 2015. Clinical factors in analysis included pretreatment PSA, clinical T-stage, histology, treatment modality and demographic factors including age, comorbidity index, race, insurance status and treatment facility type. Patients were stratified into treatment groups consisting of local therapy alone (n = 40, 60%), local therapy and chemotherapy (n = 13, 20%), chemotherapy alone (n = 7, 11%), and observation (n = 6, 9%). Survival analysis was estimated using the Kaplan-Meier method and analyzed with log-rank testing. A Cox proportional hazards model was used to evaluate the association between patient characteristics and survival. Univariable and multivariable logistic regression was performed to identify covariates associated with receipt of each treatment modality. Results: With an overall median follow-up of 21.9 months, median survival was 19.7 months for patients treated with local therapy alone, 10.9 months with chemotherapy alone, and 36.5 months with combined local therapy and chemotherapy. Overall survival was not statistically significant between treatment groups. Statistically significant predictors of death included age (HR 1.1, 95% CI [1.03-1.17]) and clinical stage ≥T3a (HR 4.05, 95% CI [1.35-12.2]). Statistically significant predictors of receipt of chemotherapy were clinical stage T3a or greater (OR 34.6, 95% CI [2.65-364]) and age (OR 0.91, 95% CI [0.82-99]). Conclusions: This analysis represents the largest reported cohort analysis of locoregional pure PSCC. Unfortunately, due to the rarity of this disease, prospective or randomized trials to determine the optimal treatment strategy are not feasible. Despite limitations in sample size, and in the absence of prospective data, this analysis suggests the addition of chemotherapy to local therapy is a reasonable treatment approach in appropriately selected patients and may result in improved survival.

Abstract PS1-17: Comparing survival differences between breast-conserving therapy and mastectomy in patients with early-stage breast cancer undergoing upfront surgery

Abstract Background: Over the last decade, patients with early-stage breast cancer have been undergoing total mastectomy (TM) with increasing frequency. Our center reported that local recurrence rates with breast conserving therapy (BCT) declined throughout the 27-year period: from 7.1% for patients treated during 1970–1984 to 1.3% for patients treated during 1994–1996. More recently, several groups have published slightly improved survival rates in patients undergoing BCT compared with TM. The aim of this study was to evaluate trends in TM rates and compare overall survival (OS), distant metastasis-free survival (DMFS), local-regional recurrence (LRR) and disease-specific survival (DSS) between BCT and TM in patients with early-stage breast cancer undergoing upfront surgery. Methods: We identified women with clinical stage T1–2, N0–1, M0 breast cancer who underwent surgery as first treatment modality from 1/1/2000 to 12/31/2014 at our center. TM rates and survival outcomes were evaluated. Because the decision for surgery for those patients was not random, differences in patient, tumor and treatment characteristics with respect to surgery types were adjusted using inverse probability weighting (IPW) based on propensity scores. Variables in the model included age at diagnosis, clinical tumor T category, clinical nodal category, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) status and year of surgery, and a multinomial logit model was used for surgery treatment assignment and a Gamma model was used for the time to censor. IPW models were used to adjust for impact of surgery types on survival outcomes. Similar analysis was used in 6 subsets: Stage I &amp; hormone receptor (HR)+/HER2-, Stage I &amp; HER2+, Stage I &amp;triple negative breast cancer (TNBC), Stage II &amp; HR+/HER2-, Stage II &amp; HER2+, Stage II &amp; TNBC. Patients undergoing TM with RT were excluded from subset analysis due to small sample size. Results: A total of 8,256 patients were included, of them, 4701 (56.9%) underwent BCT, 2862 (34.7%) underwent TM without RT and 693 (8.4%) underwent TM+RT. Patients who underwent TM were younger and were more likely to have larger tumors, positive lymph nodes, higher grade, and HER2-positive tumors. TM rates increased in patients &amp;lt;=50 years old from 2006-2013. At a median follow-up time of 6.1 years, multivariable Cox model showed that patients who underwent BCT had improved OS (HR: 0.8,95%CI: 0.7-0.99, P=0.02) and had a similar DSS, DMFS, and LRR compared to patients who underwent TM without RT. After IPW adjusting, patients undergoing BCT had a slightly worse DSS (RR: 1.2, 95%CI: 1.02-1.4, P=0.03) and similar OS, DMFS and LRR compared to patients underwent TM without RT in the whole cohort. In subset analyses, after IPW adjusting, there were no survival differences in OS, DSS, and DMFS between TM without RT and BCT. Patients with TNBC undergoing BCT had a lower LRR compared to TM (RR: 0.4, 95% CI: 0.3-0.6, P&amp;lt;0.001) regardless of clinical stage. Conclusions: In whole cohort, after IPW adjusting, patients undergoing BCT had a slightly worse DSS compared to patients underwent TM without RT, and those differences in DSS have disappeared in the subset analysis. LRR was lower in patients with TNBC breast cancer undergoing BCT although there as a similar OS, DSS and DMFS compared with TM in subset analysis. These contemporary data may help physicians in surgical decision making for patients who are candidates for either TM or BCT. Table 1. Results from multivariable Cox models for factors associated with survival outcomes and IPW adjusted models for factors associated with survival outcomesCox ModelIPW adjusting modelsFactorsHRP95%CIRRP95% CIOSSurgery typeTM without RTBCT0.80.020.70.991.01.00.9-1.1TM with RT1.00.960.81.31.10.60.9-1.3DSSSurgery typeTM without RTRefBCT1.10.40.81.51.20.031.02-1.4TM with RT1.70.0051.22.61.30.021.04-1.6DMFSSurgery typeTM without RTRefBCT1.10.40.91.41.00.50.9-1.2TM with RT1.70.0021.22.40.90.70.7-1.2 LRRSurgery typeTM without RTRefBCT1.30.11.01.71.00.70.7-1.2TM with RT0.40.020.20.90.80.10.6-1.1Subsets IPW adjusted models for factors associated with LRRBCT vs. TM without RTStage I &amp; HR+/HER2-No. of patientsTM without RT/BCTRRP95% CIStage I &amp; HER2+1469/29451.00.90.8-1.3Stage I &amp; TNBC199/2850.70.30.3-1.5Stage II &amp; HR+/HER2-128/3170.4&amp;lt;0.0010.3-0.6Stage II &amp; HER2+690/7451.10.70.7-1.8Stage II &amp; TNBC102/1080.90.50.5-1.4Stage I &amp; HR+/HER2-110/1570.50.0480.3-0.99HER2 – human epidermal growth factor receptor 2; HR – hormone receptor; TNBC – triple negative breast cancer Citation Format: Min Yi, Mariana Chavez Mac Gregor, Benjamin Smith, Abigail S Caudle, Sarah M DeSnyder, Henry M Kuerer, Kelly K Hunt. Comparing survival differences between breast-conserving therapy and mastectomy in patients with early-stage breast cancer undergoing upfront surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-17.

Abstract PS1-14: Impact of axillary dissection and patterns of care in patients with ypN1 triple negative breast cancer receiving regional nodal irradiation

Abstract Background: The benefit of axillary lymph node dissection (ALND) in patients with pN1 disease on sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy for invasive breast cancer in patients receiving regional nodal irradiation (RNI) is unclear, even in patients with high risk histologic features such as triple negative disease. We sought to determine any association of ALND with improved survival, as well as patterns of care in this cohort using the National Cancer Database (NCDB). Methods: The NCDB was queried for women ages 18-75 with cT1-3N1 and ypT0-T3N1M0 breast cancer that underwent definitive surgical resection with axillary staging followed by adjuvant regional nodal irradiation, with triple negative receptor status. Only patients who were treated from 2012 - 2015 were included for appropriate coding of the extent of axillary surgery. Overall survival was estimated using the Kaplan-Meier method and Cox proportional hazards models. An analysis of the number of lymph nodes removed, rate of RNI utilization, and rate of ALND was performed using the Wilcoxon rank-sum test, proportions of RNI utilization compared using the Chi-squared test, and correlation of these to year of diagnosis was evaluated with the Pearson correlation coefficient. Results: A total of 572 women were identified that met inclusion criteria. The median age was 53 (range 24-75) years. 67 (11.7%) of women had SLNB alone and 505 (88.3%) had ALND with or without SLNB. Four year OS was 66.7% in patients undergoing ALND compared to 70.6% in those that had SLNB alone (p = 0.47). Charlson-Deyo comorbidity index (CDCC) (p = 0.01) and clinical T3 stage (p = 0.03) were significantly associated with survival. After adjusting for age, histology, clinical and pathologic T-stage, and CDCC, there was no significant relationship between receipt of ALND and overall survival (OS), however CDCC (p = 0.01) and cT3 or pT3 (p = 0.02 and p =0.01) remained significantly associated with OS. The mean number of lymph nodes sampled from 2012 to 2015 increased from 11.68 to 13.46 (p = 0.07). The rate of RNI increased from 55.6% in 2012 of patients to 58.4% in 2015 (p = 0.6). The rate of ALND increased from 83.9% in 2012 to 90.8% in 2015 (p = 0.2). Pearson correlation coefficients between mean number of lymph nodes sampled, rate of RNI, and rate of ALND were 0.83. 0.13, and 0.95 respectively. Conclusions: There was no difference in overall survival between patients with cT1-3N1M0 and ypT0-3N1M0 triple negative breast cancer receiving SLNB compared to ALND with adjuvant RNI, even when adjusting for tumor size and comorbidities, which remained significant risk factors. There was a trend towards an increase in the mean number of lymph nodes sampled and increased utilization of ALND, though these failed to reach statistical significance. We await the results of the Alliance 011202 randomized trial to provide prospective guidance of the utility of ALND in this high risk subgroup. Table 1. Baseline Characteristics For Triple-Negative PatientsSLNB (n=67)ALND (n=505)Median Age (Years)5353Histology (n, %)Ductal61 (91%)452 (90%)Lobular2 (3%)15 (3%)Other4 (6%)38 (7%)T-Stage (n,%)cT111 (16%)73 (15%)cT234 (51%)290 (57%)cT322 (33%)142 (28%)CDCC (n,%)054 (81%)441 (87%)19 (13%)51 (10%)24 (6%)8 (2%)30 (0%)5 (1%)Mean CDCC0.250.16Facility Type (n,%)Community5 (7%)36 (7%)Comprehensive Community27 (40%)171 (34%)Academic/Research13 (19%)160 (32%)Integrated Network13 (19%)72 (14%)Other/Unknown9 (14%)66 (13%)Lymphovascular Invasion (%)32.84%32.48%Median Tumor Size (cm)3.63.3Median Nodes Examined412Median Nodes Positive12 Citation Format: Michael Kharouta, Nicholas Damico, Megan Miller, Eleanor Harris, Janice Lyons. Impact of axillary dissection and patterns of care in patients with ypN1 triple negative breast cancer receiving regional nodal irradiation [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-14.

Abstract PS12-06: Phase II randomized trial of fulvestrant with or without enzalutamide in ER+/Her2- primary breast cancer (BC)

Abstract Background: Almost all ER+ breast cancers express androgen receptor (AR), but its function is uncertain. AR expression is associated with more indolent tumors, however high AR expression relative to ER is associated with endocrine resistance, and in the absence of estradiol or if ER function is blocked, preclinical data would suggest that AR can take over to signal cell survival and proliferation. This non-blinded randomized phase II trial of neoadjuvant fulvestrant with or without enzalutamide was performed in women with T2 or greater ER+/Her2- primary breast cancer. Methods: Eligible patients were women with ECOG 0-2, ER+/Her2- primary breast cancer cT2 or greater. A total of 4 months of therapy was given (fulvestrant 500 mg IM weeks 1, 3, 5, 9, and 13). Patients were randomized to receive enzalutamide 160 mg po daily on a continual basis for 16 weeks. Stratification factors were clinical node status (N0 vs N1/2) and T-stage (T2 vs T3/4). Surgery was planned for week 17. Fresh tumor biopsies were required at study entry and at ~4 weeks on therapy. Tissue, both fresh frozen and FFPE, was also obtained at time of surgery. The PEPI score at time of surgery was the primary endpoint for efficacy. The statistical design were parallel phase II trials with the experimental arm designed as a Simon 2-stage. The expectation for the control arm was a PEPI score of 0 in 16% and 32% for the combination arm. Additional enrollment of 12 patients would ensue if 4 or more achieved a PEPI score of 0 within the first 22 patients enrolled onto the combination arm. 27 patients would be enrolled into the fulvestrant alone arm. Results: The Simon 2-stage criteria were met and the trial continues to accrue up to 11 more evaluable patients. Thus far, 58 patients were consented of whom 50 were treated. Median age was 61.5 years (45-83); PS 0 (0-2). Among the 46 patients with information on AEs, there are 25 patients with Grade 2 AEs, including 5 with fatigue, 3 with headache, and 2 with hot flashes. There are 5 patients with grade 3 AEs including abdominal pain, gallbladder obstruction, ALT elevation, hyperglycemia, and hypertension. We also have 2 patients with grade 4 AEs , chest pain-cardiac and cardiac disorder-other. There is no grade 5 event. Paired samples at baseline and at 4 weeks are collected so far from 49 patients. 42 patients have completed surgery, while two patients have not undergone surgery. Conclusions: The combination of fulvestrant plus enzalutamide had manageable side effects. The trial is now in its extended stage since PEPI score = 0 was achieved in at least 4 of the first 22 patients on the combination arm. Extensive molecular studies of paired fresh biopsies from pretreatment and at 4 weeks are underway. These analyses and correlations with clinical outcome will be described. Citation Format: Anthony D Elias, Monica Fournier, Gregory A Vidal, Sharon Sams, Nicole Spoelsta, Peter Kabos, Jennifer R Diamond, Elena Shagisultanova, Anosheh Afghahi, Jose Mayordomo, Julia Wulfkuhle, Emanuel Petricoin, Lisa Carter, Kathryn Zolman, Stephanie Armstead, Alyse Winchester, Tessa McSpadden, Gloria Crawford, Virginia Borges, Dexiang Gao, Jennifer Richer. Phase II randomized trial of fulvestrant with or without enzalutamide in ER+/Her2- primary breast cancer (BC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-06.

Abstract OT-19-01: Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer

Abstract Background: Breast conserving therapy is an established option for early stage breast cancer. Shorter postoperative radiotherapy (RT) regimens have similar efficacy in lower risk breast cancer, including hypofractionated whole breast RT and Accelerated Partial Breast Irradiation (APBI). Despite similar efficacy results for APBI, RAPID trial showed worse cosmetic outcomes for patients receiving APBI compared to whole breast RT. Larger postoperative lumpectomy cavity volumes and the used dose regimen could have had an impact on cosmesis. There are only few published preoperative APBI pilot studies with different dosimetric schemes treating smaller RT target volumes that would potentially translate into less toxicity. Our study is designed to evaluate the safety and feasibility of preoperative ablative RT in patients with early stage breast cancer. An array of ancillary imaging, blood and tissue biomarker collection is also planned in order to study the radiation response in breast cancer. Trial Design: This phase I study uses a modification of the standard 3+3 Phase I design to identify the recommended phase 2 dose of preoperative SABER for treatment of selected breast cancer patients. Participants will be treated with assigned dose level of preoperative SABER, once a day, for 5 fractions given on non-consecutive days, over a period of 2 weeks. The tested dose levels are: Level I=35 Gy (7 Gy x 5), Level II (starting dose)= 40 Gy (8 Gy x 5), Level III=45 Gy (9 Gy x 5), Level IV=50 Gy (10 Gy x 5). Standard partial mastectomy and axillary surgery will be performed 4-6 weeks after preoperative SABER. Adjuvant systemic therapy will be per standard of care. Exploratory studies will be performed pre/post RT and postoperative, including multiparametric breast MRI, biomarkers in blood (CTC’s, SNPs, cytokines, CRP) and tissue (assessment of radiation response, expression of PD-L1, PD1, TILs). Cosmesis and QoL assessment will be performed at scheduled 1, 6, 12, 24 months follow-up. Eligibility criteria: Women, 50 or older, clinical stage T1 unifocal, N0, ER/PR+/HER2 negative, ECOG 0-1, able to undergo MRI with contrast are eligible. Specific Aims: Aim 1. To identify the recommended phase II dose of preoperative SABER; Aims 2.a) to determine the safety, tolerability, Dose Limiting Toxicity (DLT) and toxicity profile of delivering SABER; b) to determine the rate of complete pathological response after preoperative SABER; c) To assess cosmetic results (by MD and patient’s assessment) and QoL after SABER and standard partial mastectomy/axillary surgery. Exploratory aims: a) to determine biomarkers in blood and tissue, and multiparametric MRI radiographic changes and associate them with toxicity and radiation tumor response; b) to assess locoregional recurrence, disease-free survival, and overall survival; c) to assess sentinel lymph node biopsy identification rates after SABER. Statistical Methods: In this novel phase I study, escalation to the next higher dose level will occur only if 0 or only 1 out of 6 patients has DLT. Present accrual and target accrual: A total of 12 to 18 evaluable patients will be enrolled. Expected enrollment period is 3 years and time to complete the study is about 5 years. Open for accrual in 06/2020. Clinical trial information: NCT04360330 Citation Format: Cristiane Takita, Isildinha M. Reis, Radka Stoyanova, John C. Ford, Brian Marples, Jose Net, Monica Yepes, Carmen Gomez, Susan Kesmodel. Phase I study to evaluate the safety and feasibility of preoperative ablative radiotherapy (SABER) for selected early stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-19-01.

Association of total neoadjuvant therapy with favorable clinical outcomes in patients with locally advanced esophageal and gastroesophageal junction adenocarcinomas (LA-GEJ CA).

231 Background: Both peri-operative chemotherapy and neoadjuvant chemoradiation have been shown to improve outcomes in patients (pts) with LA-GEJ CA compared to surgery alone. Rates of post-operative chemotherapy delivery remain suboptimal. Total neo-adjuvant therapy (TNT) in LA-GEJ CA - induction chemotherapy (IC) followed by concurrent chemoradiation (CRT) - may improve systematic delivery of neoadjuvant therapy and result in favorable clinical outcomes. Methods: We retrospectively reviewed medical records of 135 pts with LA-GEJ CA at our institution between 2/2007 and 11/2019; pertinent clinical data were abstracted with Institutional Review Board approval. Patients treated with IC and curative-intent CRT with ≥40 Gy dose of radiation for adenocarcinoma were included in this analysis (N = 59). Doublet or triplet IC regimens utilizing 5-Flurouracil(5-FU), Cisplatin/Oxaliplatin and Docetaxel were commonly administered while combinations of Carboplatin +Paclitaxel or 5-FU + Oxaliplatin were used in CRT. Clinical complete response (CCR) was defined as metabolic imaging and endoscopic biopsies negative for residual malignancy after completion of TNT. Patients were followed from diagnosis to recurrence and overall survival. Survival probabilities were estimated using the Kaplan-Meier method and compared between groups using a log-rank test. Results: Out of 59 evaluable pts, 69% were clinical stage T3, 71% were node positive. 37 pts (63%) underwent surgery, R0 resection rate was 89% (33/37), pathologic complete response (pCR) rate was 19% (7/37). Among the pts who did not undergo surgery, 41% (9/22) opted to forego surgery since they attained a CCR. For the entire cohort, median Disease-Free Survival (mDFS), median Overall Survival (mOS), and 3-yr OS were 2.4 yrs, 4.7 yrs, and 67% respectively. Pts who did not undergo surgery had a mDFS, mOS, and 3-yr OS of 1.5 yrs, 4.2 yrs, and 59% respectively. Median DFS, mOS, and 3-yr OS of patients who underwent surgery were 3.5 yrs, 5.8 yrs and 72% respectively. Patients who achieved a CCR and opted to forego surgery (N = 9) had a 3 -yr DFS of 42% vs 83% for pts (N = 7) who demonstrated a pCR after curative intent tri-modality therapy. (P = 0.0099) Interestingly, the same group that achieved CCR and opted out of surgery had 3yr OS of 89% vs 83% of those who demonstrated a pCR (p = 0.0042). Conclusions: TNT for pts with LA-GEJ CA is associated with high rates of R0 resection as well as excellent DFS and OS compared to historical controls, warranting prospective evaluation. The remarkable DFS and OS in patients who opted to forego surgery due to achieving CCR is reflective of the local and systemic control rendered by this approach. Careful characterization and close longitudinal follow-up of patients who achieve CCR may help identify a subgroup of LA-GEJ CA pts who may benefit from surgery sparing approaches.