Nonmetastatic Rectal Adenocarcinoma Research Articles

Association of Surgical Approaches and Outcomes in Total Mesorectal Excision and Margin Status for Rectal Cancer

IntroductionDespite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer. MethodsPatients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected from the US Rectal Cancer Consortium database (2007-2017). Quasi-Poisson regression analysis with backward selection was used to investigate the relationship between the surgical approach and outcomes of interest. ResultsAmong the 664 patients included in the study, the distribution of surgical approaches was as follows: 351 (52.9%) underwent TME via the open approach, 159 (23.9%) via the robotic approach, and 154 (23.2%) via the laparoscopic approach. There were no significant differences in baseline demographics among the three cohorts. The laparoscopic cohort had fewer patients with low rectal cancer (<6 cm from the anal verge) than the robotic and open cohorts (Lap 28.6% versus Rob 59.1% versus Open 45.6%, P = 0.015). Patients who underwent Rob and Lap TME had lower intraoperative blood loss compared with the Open approach (Rob 200 mL [Q1, Q3: 100.0, 300.0] versus Lap 150 mL [Q1, Q3: 75.0, 250.0] versus Open 300 mL [Q1, Q3: 150.0, 600.0], P < 0.001). There was no difference in the operative time (Rob 243 min [Q1, Q3: 203.8, 300.2] versus Lap 241 min [Q1, Q3: 186, 336] versus Open 226 min [Q1, Q3: 178, 315.8], P = 0.309) between the three approaches. Postoperative length of stay was shorter with robotic and laparoscopic approach compared to open approach (Rob 5.0 d [Q1, Q3: 4, 8.2] versus Lap 5 d [Q1, Q3: 4, 8] versus Open 7.0 d [Q1, Q3: 5, 9], P < 0.001). There was no statistically significant difference in the quality of TME between the robotic, laparoscopic, and open approaches (79.2%, 64.9%, and 64.7%, respectively; P = 0.46). The margin positivity rate, a composite of circumferential margin and distal margin, was higher with the robotic and open approaches than with the laparoscopic approach (Rob 8.2% versus Open 6.6% versus Lap 1.9%, P = 0.17), Rob versus Lap (odds ratio 0.21; 95% confidence interval 0.05, 0.83) and Rob versus Open (odds ratio 0.5; 95% confidence interval 0.22, 1.12). There was no difference in long-term survival, including overall survival and recurrence-free survival, between patients who underwent robotic, laparoscopic, or open TME (Figure 1). ConclusionsIn patients undergoing surgery with curative intent for rectal cancer, we did not observe a difference in the quality of TME between the robotic, laparoscopic, or open approaches. Robotic and open TME compared to laparoscopic TME were associated with higher margin positivity rates in our study. This was likely due to the higher percentage of low rectal cancers in the robotic and open cohorts. We also reported no significant differences in overall survival and recurrence-free survival between the aforementioned surgical techniques.

Reporting of Circumferential Resection Margin in Rectal Cancer Surgery

Circumferential resection margin (CRM) in rectal cancer surgery is a major prognostic indicator associated with local recurrence and overall survival. Facility rates of CRM positivity have recently been established as a new quality measure by the Commission on Cancer (CoC); however, the completeness of CRM status reporting is not well characterized. To describe the changes in CRM reporting and factors associated with low rates of reporting. A retrospective cohort study was conducted using data from the National Cancer Database between January 2010 and December 2019. Data were analyzed between October 1, 2021, and February 1, 2022. Data from the National Cancer Database included patients diagnosed with nonmetastatic rectal adenocarcinoma receiving surgical treatment at CoC-accredited facilities throughout the US. Patient, tumor, and facility-level factors. Facilities were divided by surgical volume, safety-net status, and CoC facility type. Circumferential resection margin missingness rates. A total of 110 571 patients (59.3% men) with rectal adenocarcinoma who underwent curative-intent surgery at 1307 CoC-accredited hospitals were included for analysis. Reporting of CRM improved over the study period, with a mean (SE) missing 12.0% (0.32%) decreased from 16.3% (0.36%). Academic facilities had a higher missingness than other facility types (14.3% vs 10.5%-12.7%; P < .001). Mean (SE) rates of missingness were similar between hospitals of varying volume (lowest quartile: 12.2% [0.93%] vs highest quartile: 12.4% [0.53%]; P = .96). Cases in which fewer than 12 lymph nodes were removed had higher rates of missingness (18.1% vs 11.4%; P < .001). Increased odds of CRM missingness were noted with T category (odds ratio [OR], 1.50; 95% CI, 1.35-1.65) and N category (OR, 2.00; 95% CI, 1.82-2.20). Black race was associated with missingness (OR, 1.13; 95% CI, 1.06-1.14). Although CRM positivity reporting has improved over the last decade, the findings of this study suggest there is substantial room for improvement as it becomes a quality standard. Missingness appears to be associated with poor performance on other quality metrics and facility type. This measure appears to be ideal for targeted institution-level feedback to improve quality of care nationally.

Is there an increase in elective utilization of non-operative management for rectal cancer?

e15533 Background: There is growing evidence for the efficacy of a watch-and-wait or nonoperative management (NOM) strategy following chemoradiation with or without total neoadjuvant therapy for rectal cancer as an approach to organ preservation. Consequently, there has been growing interest and acceptance of this approach among both patients and providers. This study aims to analyze the use of the NOM strategy for patients with non-metastatic rectal cancer over the past decade and the patient and facility-level factors associated with its utilization. Methods: We performed an observational cohort study identifying patients from the National Cancer Database diagnosed between 2010-2020 with invasive, non-metastatic rectal adenocarcinoma. Patients who received chemotherapy and radiation without surgery were categorized as having received NOM. All other patients who received curative-intent surgery with or without chemotherapy and radiation were classified as the standard of care (SOC) cohort. Utilization of NOM was analyzed over time. Logistic regression analysis was utilized to identify patient and facility-level factors associated with NOM. Results: In total, 107,786 patients were included for analysis, of which 14,870 (13.8%) received NOM over the study period and 92,916 (86.2%) received SOC. The use of NOM steadily increased over the study period, from 10.3% in 2010 to 20.7% in 2020. Compared to SOC, NOM was associated with patients who were Black (16.9% vs 13.6% White, p &lt; 0.001), had Medicaid or no insurance (15.3% vs 13.4% Private/Medicare insurance, p &lt; 0.001), were older than 75 years (18.9% vs 12.8% younger than 75, p &lt; 0.001), and had high Charlson-Deyo comorbidity score (16.2% vs 14.0% no comorbidities, p &lt; 0.001). Facility factors associated with greater use of NOM included treatment at community cancer programs (OR 1.44, 95% CI 1.35-1.54, p &lt; 0.001) compared to treatment at comprehensive cancer centers. Facilities stratified by incident rectal cancer patient volume demonstrated an inverse relationship with NOM management, with low volume institutions having the highest NOM rate (p &lt; 0.001). Subgroup analysis of patients &lt; 75 years old, with private insurance, and without co-morbidities treated at institutions in the top quartile of volume showed NOM rates to similarly increase over the study period, from 6.4% to 13.7% (p &lt; 0.001). Conclusions: The use of the NOM strategy for patients with non-metastatic rectal cancer has increased over the past decade. While traditionally an approach for patients who were poor surgical candidates, the increasing trend for NOM among younger patients with fewer comorbidities and private insurance suggests that there is growing interest in elective NOM over the past decade. Ongoing prospective studies of NOM will shed light regarding the long-term efficacy of this approach compared to traditional surgical SOC.

Organ preservation and total neoadjuvant therapy for rectal cancer: Investigating long course chemoradiation versus short course radiation therapy.

3617 Background: The efficacy of long course chemoradiation (LCRT) vs. short course radiation therapy (SCRT) relative to organ preservation (OP) in rectal cancer (RC) is unknown. We compared OP rates between SCRT and LCRT total neoadjuvant therapy (TNT) strategies. Methods: During the COVID-19 pandemic we established an institutional SCRT mandate with no exceptions. For comparison, we identified RC patients treated with LCRT immediately before and after the mandate period. After completion of TNT, patients were restaged by clinical exam, endoscopy, and MRI. A watch and wait (WW) approach was recommended for patients with a clinical complete response (cCR), defined by the MSK regression schema. Total mesorectal excision (TME) was recommended for non-cCR patients. OP was defined as remaining TME-free with no evidence of disease in the pelvis. We performed survival analysis for: local regrowth rate, OP, disease-free survival (DFS), and overall survival (OS). The validated low anterior resection syndrome (LARS) questionnaire (LARS-Q) was used to determine percentage of patients with major LARS. Results: We identified 332 consecutive patients with non-metastatic rectal adenocarcinoma treated with TNT (Jan. 2018-Jan. 2021). Patient and tumor characteristics were similar in the LCRT (n = 256) and SCRT (n = 76) cohorts. No significant differences in high-risk features were noted. Most patients had clinical stage III disease (82% in LCRT vs. 83% in SCRT). Induction chemotherapy followed by consolidative radiation was the most common treatment order (78% (LCRT) vs. 70% (SCRT)). The median interval from end of TNT to clinical restaging was 8 weeks (LCRT) and 9 weeks (SCRT). The cCR rate was 46% in both cohorts. Among patients with a cCR, the likelihood of WW management was similar (98% (LCRT) vs. 94% (SCRT)). From start of TNT, the median follow-up was 32 and 28 months respectively for LCRT and SCRT. The 2-year OS (95% vs. 92%), DFS (78% vs 70%), and distant recurrence (20% vs. 21%) rates were similar. Among all patients, the 2-year OP rate was 40% (95% CI 35-47%) for LCRT and 29% (95% CI 20-42%) with SCRT. In those patients managed by WW, the 2-year local regrowth rate was 20% (95% CI 12-27%) with LCRT vs. 36% (95% CI 16-52%) with SCRT. Percentage of patients reporting major LARS symptoms were similar among WW patients post TNT: baseline (23% (LCRT) vs. 18% (SCRT)), 6-months (41% (LCRT) vs. 42% (SCRT)), and 12-months (25% (LCRT) vs. 15% (SCRT)). Conclusions: In this nonrandomized comparison, while cCR rates were similar, we observed a numerically higher local regrowth rate with SCRT-TNT than with LCRT-TNT. Rate of major-LARS symptoms were similar with LCRT-TNT than with SCRT-TNT. The ongoing ACO/ARO/AIO-18.1 trial, hypothesizing that LCRT-TNT will increase OP rates relative to SCRT-TNT, will definitively address this question.

Concordance between clinical and pathologic assessment of T and N stages of rectal adenocarcinoma patients who underwent surgery without neoadjuvant therapy: A National Cancer Database analysis.

Clinical assessment of T and N stages in rectal cancer is important to guide decision-making. The present study aimed to assess the accuracy of the clinical T and N staging of rectal cancer compared to the pathological staging and their overall agreement in a large cohort of patients. This retrospective study used data from the National Cancer Database (NCDB) between 2004 and 2017. Patients with non-metastatic rectal adenocarcinoma who did not receive neoadjuvant therapy were reviewed and the clinical T and N stages were compared to their pathologic counterparts. The overall concordance between clinical and pathologic assessments was calculated using Kappa coefficient. The study included 8929 patients (57.3% male) with a mean age of 64 years. Clinical T stage and N stage were identical to pathologic stages in 70.3% and 77.6% of patients, respectively. Sensitivity and specificity of the clinical assessment of N stage was 35.2% and 95.5%, respectively. Concordance between the clinical and pathologic stages was moderate for the T stage (kappa=0.575) and fair for the N stage (kappa=0.346). Pathologic T4 stage (OR: 2.12, p<0.0001), poorly differentiated adenocarcinoma (OR: 1.45, p=0.026), lymphovascular invasion (OR: 4.5, p<0.001), and longer time from diagnosis to first treatment (OR=0.996, p=0.046) were the independent predictors of N stage discrepancy. There was a moderate agreement between the clinical and pathologic T stages and a fair agreement between the clinical and pathologic N stages. The clinical assessment of the N stage was highly specific yet had low sensitivity.

Outcomes of laparoscopic versus robotic-assisted resection of T4 rectal cancer: propensity score-matched analysis of a national cancer database.

T4 rectal cancer is a challenging condition owing to the highly invasive nature of the tumour that may compromise R0 resection. The present study aimed to assess the outcomes of laparoscopic versus robotic-assisted resection of non-metastatic T4 rectal adenocarcinoma. This was a retrospective propensity score-matched analysis using the National Cancer Database between 2010 and 2019. Patients with pathological T4 non-metastatic rectal adenocarcinoma who underwent laparoscopic or robotic-assisted resection were compared and a propensity score-matched analysis was performed in a 1:1 manner. The main outcome measures were conversion to open surgery, mortality, readmission, resection margins, and overall survival. After propensity score matching, 235 patients were included in each group. There were 260 (55.3 per cent) men and 210 (44.7 per cent) women, with a mean (s.d.) age of 61 (13.2) years. Patients in the robotic group had a statistically significantly lower conversion rate (8.9 per cent versus 17.9 per cent; P = 0.006), shorter median duration of hospital stay (5 versus 6 days; P = 0.007), higher overall survival rate (56.2 per cent versus 43.4 per cent; P = 0.007), and a longer median survival (60.8 versus 43.2; P = 0.025). There were no significant differences between the two groups with regard to positive resection margins, examined lymph nodes, 30-day and 90-day mortality rates, and 30-day readmission rate. Robotic resections of T4 rectal cancer were associated with a significantly lower conversion rate and shorter duration of hospital stay than laparoscopic resections. The two approaches were comparable with regard to positive resection margins, short-term mortality, and readmission.

Factors associated with refusing surgery versus planned nonoperative management for rectal cancer

BackgroundIncreasingly, patients with rectal cancer receive nonoperative management. A growing body of retrospective evidence supporting the safety of this approach has likely contributed to its growing popularity. However, patients may also undergo nonoperative management because of refusal of surgical resection. We hypothesize that patients who refuse surgery are more likely to be from groups who traditionally face barriers accessing care. MethodsWe used the National Cancer Database (2006–2017) to analyze patients with nonmetastatic rectal adenocarcinoma who underwent nonoperative management following radiation. We identified 2 groups: (1) planned nonoperative management and (2) nonoperative management because of refusal of surgery. We performed logistic regression to compare the groups along patient, socioeconomic, and facility-level factors. ResultsIn total, 9,613 and 2,039 patients were included in the planned nonoperative management and refused nonoperative management groups, respectively. Of the total study cohort (ie, planned nonoperative management + refused nonoperative management), 21% of these patients diagnosed in 2017 underwent refused nonoperative management, versus 12% in 2006. Patients who were Black (adjusted odds ratio 1.47, 95% confidence interval 1.26–1.71) or Asian/Pacific Islander (adjusted odds ratio 1.51, 95% confidence interval 1.18–1.92), age ≥65 years (adjusted odds ratio 1.55, 95% confidence interval 1.37–1.77), with more advanced disease stage (stage III adjusted odds ratio 1.30, 95% confidence interval 1.10–1.53), and government insurance (adjusted odds ratio 1.19, 95% confidence interval 1.04–1.36) were associated with increased utilization of refused nonoperative management. Conversely, lower education (adjusted odds ratio 0.62, 95% confidence interval 0.50–0.76) and female sex (adjusted odds ratio 0.88, 95% confidence interval 0.79–0.97) were associated with planned nonoperative management. ConclusionOur findings suggest that the refused nonoperative management group is demographically distinct. Outreach efforts to better understand the rationale behind patient decision making in rectal cancer will be paramount to ensuring appropriate implementation of nonoperative management.

Minimally invasive, 'en-bloc' seminal vesicle excision for locally advanced rectal adenocarcinoma: surgical technique and short-term outcomes.

Isolated seminal vesicle invasion is a rare occurrence in patients with locally advanced rectal cancers. This study describes the surgical technique and the perioperative outcomes of minimally invasive 'en-bloc' seminal vesicle excision, preserving the bladder and the prostate. A retrospective review of 23 consecutive patients who underwent minimally invasive, en-bloc resection of seminal vesicles for locally advanced, non-metastatic rectal adenocarcinoma between May 2016 and November 2021. Perioperative outcomes and short-term oncological outcomes were defined. Eighteen patients underwent a laparoscopic procedure while five received a robotic resection. All patients received preoperative radiation with or without consolidation chemotherapy. The median age was 42 years (range 20-64 years) and the median hospital stay was 8 days (range 3-19 days), respectively. Serious complications (Clavien-Dindo ≥ IIIb) were seen in six patients (26.1%). Two patients (8.7%) had an involved circumferential resection margin. At a median follow up of 19 months (range 2-52 months), four patients developed recurrences. The 2-year overall and disease-free survival was 84.4% and 73.6%, respectively. Minimally invasive, en-bloc resection of one or both seminal vesicles for locally advanced rectal adenocarcinoma, is feasible in a select group of patients with acceptable morbidity and short-term outcomes.

High dose chemoradiotherapy increases chance of organ preservation with satisfactory functional outcome for rectal cancer

BackgroundHigh dose chemoradiotherapy offers a curative chance for patients with rectal cancer that are unfit or unwilling to undergo surgical resection, yet its long-term survival and functional outcomes have been rarely investigated.MethodsPatients with non-metastatic rectal adenocarcinoma who received pelvic radiation for curative intent from April 2006 to July 2017 were retrospectively investigated. Survival rates were analyzed using the Kaplan–Meier method. Quality of life and functional outcomes were evaluated using the EORTC quality of life questionnaire.ResultsA total of 57 patients were included, with a median age of 59.0 (range, 29–84) years. The numbers of patients who were diagnosed as stage I, II and III were 5 (8.8%), 16 (28.1%) and 36 (63.2%), respectively. 53 (93.0%) patients had tumor located within 5 cm from the anal verge. All patients received fluorouracil-based concurrent chemoradiotherapy with a median radiation dose of 80 (range, 60–86) Gy. All kinds of grade 3–4 adverse events occurred in 18 (31.6%) patients. 42 (73.7%) patients achieved a clinical complete response after chemoradiotherapy. After a median follow-up of 43.5 (range 14.9–163.2) months, 12 (21.1%) patients had local progression and 11 (19.3%) developed distant metastasis. The 3-year local recurrence-free survival and distant metastasis-free survival were 77.3% (95% CI, 65.7–88.8%) and 79.2% (95% CI, 68.2–90.2%), while the 3-year progression-free survival, cancer-specific survival, overall survival were 61.9% (95% CI, 48.8–75.0%), 93.1% (95% CI, 85.8–100.0%) and 91.4% (95% CI, 83.6–99.2%), respectively. For patients who had tumor located within 3 cm from the anal verge, the sphincter preservation rate was 85.3% at last follow-up. Long-term adverse events mainly were anal blood loss. 21 patients completed the quality-of-life questionnaire and had a score of the global health status of 78.57 ± 17.59. Of them, 95.2% reported no urinary incontinence and 85.7% reported no fecal incontinence.ConclusionsHigh dose chemoradiation demonstrated promising survival outcomes with acceptable short-term and long-term side effects, and satisfying long-term functional outcomes and quality of life. It could be considered as a non-invasive alternative for rectal cancer patients who refuse surgery.

Construction of a predictive model for clinical survival in male patients with non-metastatic rectal adenocarcinoma

BackgroundNo clinical prediction model is available for non-metastatic rectal adenocarcinoma in males. Based on demographic and clinicopathological characteristics, we constructed a survival prediction model for the study population. MethodsAt a ratio of 7:3, 3450 eligible patients were divided into training and validation sets. Optimal cutoff values were calculated using X-tile software. Cox proportional hazards regression was used to find prognostic factors for cancer-specific survival (CSS) and overall survival (OS). Corresponding nomogram prognostic models were also constructed based on predictors.The validity, discriminative ability, predictability, and clinical usefulness of the model were analyzed and assessed. ResultsWe identified predictors of survival in the target population and successfully constructed nomograms. In the nomogram prediction model for OS and CSS, the C-index was 0.724 and 0.735, respectively, for the training group and 0.754 and 0.760, respectively, for the validation group. In the validation group, the area under the curve (AUC) of the receiver operating characteristic curve for OS and CSS nomograms was 0.768 and 0.769, respectively, for the 3-year survival rate and 0.755 and 0.747, respectively, for the 5-year survival rate. Kaplan–Meier Survival Curves showed excellent risk discrimination performance of the nomogram (P < 0.05) Calibration curves, time-dependent AUC and decision curve analysis showed that the prediction model constructed in this study had excellent clinical prediction and decision ability and performed better than the TNM staging system. ConclusionOur nomogram is helpful to evaluate the prognosis of non-metastatic male patients with rectal adenocarcinoma and has guiding significance for clinical treatment.

A PROSPECTIVE COMPARATIVE STUDY ON LOCALLY ADVANCED RECTAL CARCINOMA TREATED WITH PRE-OPERATIVE SHORT-COURSE RADIOTHERAPY VERSUS LONG-COURSE RADIOTHERAPY WITH CONCOMITANT CHEMOTHERAPY

Objective: In locally advanced non-metastatic rectal carcinoma, pre-operative radiotherapy is an acceptable alternative over post-operative radiation to improve locoregional control after radical surgery. There are two regimens of pre-operative radiotherapy – short-course radiotherapy (25 Gy/5 fractions/1 week) and long-course chemoradiotherapy (CRT) (50.4 Gy/28 fractions/5.5 weeks). Our study aimed to compare the pathological response, margin negative surgery rates, and treatment-related acute toxicities between these two approaches. Methods: Patients with histologically proven locally advanced, non-metastatic rectal adenocarcinoma were randomized into study group and control group – the study group received short-course radiotherapy (25 Gy/5 fractions/1 week) followed by surgery after 7–10 days of completion of radiotherapy and the control group received long-course radiotherapy (50.4 Gy/28 fractions/5.5 weeks) with concurrent capecitabine followed by surgery after 4–6 weeks of completion of radiotherapy. Histopathology reports were studied in both groups for the determination of pathological response of tumor and surgical margin status. All patients received adjuvant chemotherapy for 6 months with oxaliplatin and capecitabine. For the assessment of treatment-related acute toxicities, patients were examined during the entire course of treatment. Results: Overall pathological response (complete response+partial response) was 81.25% in the study arm and 86.66% in the control arm. Complete response rate was 15% in the study arm and 25% in the control arm. Margin negative surgery rates were higher in long-course CRT than short-course radiotherapy (90% vs. 82%), but it was statistically insignificant. Radiation-induced acute skin reactions (less than Grade 2) were significantly higher in long-course CRT arm (p=0.003). Conclusion: There is no significant difference between pre-operative short-course radiotherapy and long-course concomitant CRT in terms of efficacy and acute toxicity profile. Thus, with our limited resources and huge patient load, short-course radiotherapy can be used as an acceptable alternative to long-course CRT.

Nonmetastatic ypt0 rectal cancer after neoadjuvant treatment and total mesorectal excision: Lessons from a retrospective multicentric cohort of 383 patients

BackgroundA better understanding of pathological features and oncological survival in ypT0 rectal cancer after neoadjuvant chemoradiotherapy is required to improve patient selection criteria for rectal-preserving approach by local excision. Our aim was to define risk of lymph node metastasis and oncological outcomes in ypT0 rectal cancer after chemoradiotherapy and total mesorectal excision. MethodsAll consecutive patients who underwent total mesorectal excision for a nonmetastatic rectal adenocarcinoma classified ypT0 after neoadjuvant chemoradiotherapy, with or without locoregional lymph node involvement (ypN+ or ypN-), in 14 French academic centers between 2002 and 2015 were included. Data were collected retrospectively. Overall and disease-free survival were explored. ResultsAmong the 383 ypT0 patients, 6% were ypN+ (23/283). Before chemoradiotherapy, 86% (327/380) were staged cT3-T4 and 41% (156/378) were staged cN+. The risk of ypN+ did not differ between cT3-T4 and cT1-T2 patients (P = .345) or between cN+ and cN- patients (P = .384). After a median follow-up of 61.1 months, we observed 95% confidence interval (92%–97%) of 5-year overall survival and 93% confidence interval (91%–96%) of 5-year disease-free survival. In Cox multivariate analysis, overall survival was altered by intra-abdominal septic complications (hazard ratio = 2.53, confidence interval [1.11–5.78], P = .028). Regarding disease-free survival, ypN+ status and administration of adjuvant chemotherapy were associated with a reduced disease-free survival (P = .001 for both). cT3/T4 staging and cN+ staging did not modify overall survival (P = .332 and P = .450) nor disease-free survival (P = .862 and P = .124). ConclusionThe risk of lymph node metastasis and the oncological survival do not depend on the initial cT or cN staging in cases of ypT0 complete rectal tumor regression.

Dosimetry Evaluation of Locally Advanced Rectal Adenocarcinoma Treated With Short-Course Radiotherapy and Sequential Multi-Agent Chemotherapy With Non-Operative Intent

Short course radiotherapy (SCRT) followed by chemotherapy (CH) with non-operative intent is a promising treatment option for rectal adenocarcinoma. We evaluated the incidence, severity, and dosimetric predictors of acute and late toxicities for patients treated with SCRT-CH undergoing non-operative management.From January 2018 to May 2019, 90 patients with newly diagnosed, non-metastatic rectal adenocarcinoma were treated with SCRT-CH. 42 patients with cCR have not required surgical intervention to date and were included in this analysis. Patients received 25 Gy /5 fx to the pelvis with an optional primary boost to 30 Gy. Patients were evaluated every 3 months for recurrence and toxicity. Treatment plans were assessed for mean dose, max dose, V125%, V105%, V100%, V80% for the following structures: PTV, anal canal, rectum, large bowel, small bowel, and entire bowel. Toxicities were graded per CTCAEv5.0. Patients with clinically significant toxicity were compared to those without by the Mann-Whitney U test. The difference was statistically significant at the p < 0.05 level.Of the 42 patients evaluated, the average age was 61.9 years (range 24-85) and 23 (54.8%) were male. Four patients (9.5%) developed grade 3 acute gastrointestinal toxicities. The grade 3 toxicities of colitis, diarrhea, and ileus occurred during CH. One grade 3 rectal pain occurred shortly after completion of SCRT. Dosimetric parameters are reported in Table 1 below; there were no statistically significant differences (P > 0.05) in the evaluated dosimetric variables between patients with and without clinically significant toxicity. No late grade 3 or greater GI toxicities were present at last follow-up.In this dosimetric evaluation of SCRT-CH and non-operative management for rectal adenocarcinoma no dosimetric variables were associated with grade 3 or greater toxicities. These data can provide the foundation for future studies, including evaluating dose escalation, in SCRT-CH non-operative treatment.

Clinical outcomes following definitive treatment of young-onset, locally advanced rectal cancer: A single institution experience.

e15601 Background: We evaluated demographic, treatment, and survival outcomes of adults age 18 to 49 years treated at our institution with long course chemoradiotherapy (CRT) followed by total mesorectal excision (TME) for locally advanced rectal cancer. Additionally, we compared outcomes between those age &lt; 45 vs. &gt; 45 years. Methods: The records of 219 patients diagnosed with non-metastatic, clinical T3, T4, or node positive rectal adenocarcinoma and treated between April 2000 and November 2017 were reviewed for age, sex, and presenting symptoms; clinical stage and microsatellite stable (MSS)/DNA mismatch repair (MMR) proficiency status; treatments delivered and sequence; pathologic response to pre-operative therapies; and the development of locoregional recurrence (LRR), distant metastasis (DM), and secondary pelvic malignancy. The Kaplan-Meier method and Log-Rank test were used to calculate and compare disease-free survival (DFS) and overall survival (OS) rates from the date of TME. Results: The median age at diagnosis was 44 years (range 19-49) and there was no sex predominance. Rectal bleeding was the most common presenting symptom (91%), with a median time to diagnosis of 5 months. Clinical tumor/nodal categories were T1-2 in 4%, T3 in 87%, T4 in 7%, N0 in 17%, and N1–2 in 80% of patients. MSS/MMR proficient disease was identified in 95% of tumors with status reported (n = 170). CRT followed by TME and post-operative chemotherapy was the most frequent treatment sequence (n = 196), with capecitabine (n = 176) and FOLFOX (n = 115) as the predominant concurrent and post-operative chemotherapies, respectively. Pathologic complete response at both primary and nodal sites occurred in 15% of all cases and 16% of MSS/MMR proficient cases. There was no difference in sex, tumor category, nodal category, MSS/MMR proficiency status, or pathologic complete response, by age ( &lt; 45 years [n = 111] vs. &gt; 45 years [n = 108]). At a median DFS follow-up time of 5.0 years, there were 11 LRR, 40 DM (including 11 DM detected prior to/at time of TME), and 1 synchronous presentation of LRR and DM. The 5-year rate of DFS was 70.4% for age &lt; 45 years and 85.3% for age &gt; 45 years ( P = 0.02). At an OS median follow-up time of 7.5 years, there were 38 deaths. The 5-year rate of OS was 87.7% for age &lt; 45 years and 94.4% for age &gt; 45 years ( P = 0.126). Two patients developed non-rectal pelvic malignancies. Conclusions: The outcomes reported here from one of the largest single-institution series for young-onset, locally advanced rectal cancer could serve as a benchmark to evaluate newer treatment approaches. Rectal bleeding was the leading presenting symptom, with approximately half-year delay from development of symptoms to diagnosis. Most tumors were MSS/MMR proficient. At 5 years’ follow-up time, the DFS rate was lower for patients age &lt; 45 years when compared to those &gt; 45 years. Secondary pelvic malignancies were a rare occurrence.

Comparing outcomes for non-metastatic rectal cancer in academic vs. community centers: A propensity-matched analysis of the National Cancer Database

BackgroundLittle is known regarding the impact of hospital academic status on outcomes following rectal cancer surgery. We compare these outcomes for nonmetastatic rectal adenocarcinoma at academic versus community institutions. MethodsThe National Cancer Database (2010–2016) was queried for patients with nonmetastatic rectal adenocarcinoma who underwent resection. Propensity score matching was performed across facility cohorts to balance confounding covariates. Kaplan-Meier estimation and Cox-proportional hazards regression were used to analyze survival, other short and long-term outcomes were analyzed by way of logistic regression. ResultsAfter matching, 15,096 patients were included per cohort. Academic centers were associated with significantly decreased odds of conversion and positive margins with significantly increased odds of ≥12 regional nodes examined. Academic programs also had decreased odds of 30 and 90-day mortality and decreased 5-year mortality hazard. After matching for facility volume, no significant differences in outcomes between centers was seen. ConclusionsNo difference between academic and community centers in outcomes following surgery for non-metastatic rectal cancer was seen after matching for facility procedural volume.

Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial

PurposeShort-course radiation therapy (SCRT) and nonoperative management are emerging paradigms for rectal cancer treatment. This clinical trial is the first to evaluate SCRT followed by chemotherapy as a nonoperative treatment modality. MethodsPatients with nonmetastatic rectal adenocarcinoma were treated on the single-arm, Nonoperative Radiation Management of Adenocarcinoma of the Lower Rectum study of SCRT followed by chemotherapy. Patients received 25 Gy in 5 fractions to the pelvis followed by FOLFOX ×8 or CAPOX ×5 cycles. Patients with clinical complete response (cCR) underwent nonoperative surveillance. The primary end point was cCR at 1 year. Secondary end points included safety profile and anorectal function. ResultsFrom June 2016 to March 2019, 19 patients were treated (21% stage I, 32% stage II, and 47% stage III disease). At a median follow-up of 27.7 months for living patients, the 1-year cCR rate was 68%. Eighteen of 19 patients are alive without evidence of disease. Patients with cCR versus without had improved 2-year disease-free survival (93% vs 67%; P = .006), distant metastasis-free survival (100% vs 67%; P = .03), and overall survival (100% vs 67%; P = .03). Involved versus uninvolved circumferential resection margin on magnetic resonance imaging was associated with less initial cCR (40% vs 93%; P = .04). Anorectal function by Functional Assessment of Cancer Therapy-Colorectal cancer score at 1 year was not different than baseline. There were no severe late effects. ConclusionsTreatment with SCRT and chemotherapy resulted in high cCR rate, intact anorectal function, and no severe late effects.NCT02641691.

Complete Clinical Response after Short-course Radiation and Sequential Multi-agent Chemotherapy for Non-operative Treatment of Rectal Adenocarcinoma

Recent data show promise of short-course radiation (SCR) plus total neoadjuvant chemotherapy for rectal cancer. We evaluated the complete clinical response (cCR) rate and toxicity in patients who were treated with SCR followed by multi-agent chemotherapy (CH) and non-operative intent. From January 2018 to May 2019, 90 patients with newly diagnosed, non-metastatic rectal adenocarcinoma were treated with SCR-CH and non-operative intent at our institution. Patients received 25 Gy/5 fx to the pelvis with an optional primary boost to 30 Gy. Involved extra-mesorectal pelvic lymph nodes were boosted to 35 Gy. CH was initiated after RT. CR was assessed after CH by digital rectal examination, MRI pelvis, and endoscopy. Patients with a cCR were followed with these assessments every 3 months. Patients with a partial CR received surgery. Follow-up was calculated from CH completion. GI toxicity was graded per CTCAE v5. Of the 90 patients [median age 61 (range 25-91)], 86 (96%) had locally advanced disease (T3/4 or node positive) and median tumor size 4.6 cm (range 1.5-11 cm). The median distance from anal verge was 7 cm (range 0-13 cm). All patients completed prescribed RT. Five patients received CH ≤5 cycles due to poor tolerance. Among patients who completed CH ≥6 cycles, the initial cCR rate was 51% (43/85) overall and 49% (40/81) for patients with locally advanced disease. Median follow-up was 9.7 mos (range 0.7-21 mos) for living patients, and 44% (37/85) patients had continued cCR at last follow up. For patients with primaries ≤2 cm from anal verge, 6 (6/20, 30%) patients had an initial cCR and 5 (25%) patients had a continued cCR at last follow up. Among non-operative patients, 18 (49%) had no late GI toxicities and 0 had late G3/4 GI toxicities. In the 42 patients with a partial CR, 60% underwent low anterior resection, 29% underwent abdominoperineal resection, and 9.5% underwent transanal excision or proctectomy. Seven of 85 patients had local regrowth at a median of 8.5 mos (range 2.3-12 mos) after SCR-CH. Six cases occurred in non-operative patients requiring salvage surgery at a median of 6.0 (range 4.8-15) mos after completion of SCR-CH. Four (4/90, 4.4%) patients developed metastatic disease, all of whom had an initial partial CR and had undergone surgery. Our preliminary data show that SCR-CH can result in cCR and organ preservation in patients with locally advanced and/or low-lying rectal cancer with acceptable GI toxicity. Further follow-up is required to evaluate the durability of response and toxicity.Abstract 96; TablecT StageT212 (13%)T360 (67%)T418 (20%)cN StageN022 (24%)N127 (30%)N241 (46%)Group StageI5 (6%)II17 (19%)IIIA5 (6%)IIIB41 (45%)IIIC22 (24%)RT (Gy/fx)25/574 (82%)30/56 (7%)35/510 (11%)CH Cycles5 or fewer5 (6%)6-851 (56%)9-129 (10%)12 or more25 (28%)CH AgentsFOLFOX/mFOLFOX79 (88%)CAPOX7 (8%)Other4 (4%) Open table in a new tab

Nonoperative Management versus Surgery in Patients with Complete Endoscopic Response to Neoadjuvant Therapy for Rectal Cancer

There is increasing evidence that surgery can be avoided in patients with complete endoscopic response (CER) to neoadjuvant therapy (NAT) for rectal adenocarcinoma. We compare nonoperative management to surgery in such a cohort of patients from an integrated healthcare system with the hypothesis that surgery can be avoided without compromising outcomes. We retrospectively reviewed records of surgery eligible patients completing neoadjuvant chemoradiation (nCRT) for nonmetastatic rectal adenocarcinoma at our institution from January 2015 through January 2019. Treatment consisted of external beam radiotherapy to 50-54 Gy with concurrent 5FU-based chemotherapy. Additional systemic treatment was administered at the discretion of the treatment team. CER was defined as negative digital rectal exam (DRE) and negative endoscopy (flat mucosa or scar without stricture or ulceration) at the end of NAT. Patients with CER and refusing surgery underwent strict surveillance with DRE and endoscopy. MRI was frequently incorporated into surveillance. The primary endpoint was 36-month non-regrowth recurrence rate. Non-regrowth recurrence was defined as any non-luminal intrapelvic or distant metastatic recurrence. Within the study period, 464 patients completed nCRT. Median follow-up for the entire cohort was 36 months. CER to NAT was achieved in 95 patients (20%), 42 of whom had surgery, and 53 of whom were observed. Nonoperative patients were older (median age 64 vs 57 years), were less likely to have nodal involvement (45% vs 79%), had lower tumors (median distance from the anal verge 4 vs 8 cm), and were less likely to receive additional systemic therapy (59% vs 88%). Abdominoperineal resection (APR) was anticipated in 26 (49%) nonoperative patients. In the surgery group, 21 patients (50%) had pathologic complete response. In the nonoperative group, 6 patients (11%) had local regrowth (36-month actuarial rate 15%), and all patients were locally salvageable at the time of regrowth. The 36-month rate of non-regrowth recurrence was similar between groups (surgery 8% vs observation 15%, p = 0.38). There were 5 deaths in nonoperative patients (3 non-rectal cancer deaths, 2 rectal cancer deaths). There were no deaths in surgery patients. Overall survival at 36 months favored the surgical group (100% vs 88%, p = 0.03), however rectal cancer-specific survival at 36-months was similar between groups (100% vs 95%, p = 0.16). Observation is a feasible strategy that may improve quality of life without compromising disease outcomes in carefully selected patients with CER to NAT for rectal adenocarcinoma, as most patients with local regrowth are able to be salvaged. Further studies are needed to determine the effect of nonoperative management on non-salvageable recurrences in this group of patients.

Novel use of the Bakri balloon to minimize empty pelvis syndrome following laparoscopic total pelvic exenteration.

Pelvic exenteration is the only surgical option for locally advanced pelvic malignancies infiltrating the surrounding organs. The resultant pelvic void after the procedure is responsible for a number of complications, collectively termed empty pelvis syndrome (EPS). We aim to show how EPS can be minimized by presenting a case series demonstrating the surgical technique of laparoscopic total pelvic exenteration with bilateral pelvic node dissection along with a novel use of the Bakri balloon. This is a case series of three successive patients undergoing laparoscopic total pelvic exenteration for locally advanced primary, nonmetastatic rectal adenocarcinoma over a period of 1month in a specialized colorectal unit at a tertiary cancer centre. The Bakri balloon was deployed in all three patients and retained for variable time intervals postoperatively. Features of EPS were prospectively documented. In the first patient, the Bakri balloon was completely deflated and removed on postoperative day (POD) 5. The patient developed subacute intestinal obstruction which resolved with conservative management by POD 12. In the second and third patients, the Bakri balloon was deflated in a sequential manner, beginning on POD 8, until it was finally removed on POD 11. Neither of these patients had any abdominal complaints. A postoperative CT scan of both these patients showed the small bowel loops clearly above the pelvic inlet. The Bakri balloon is a simple, safe and cost-effective method to reduce the complications of EPS following laparoscopic total pelvic exenteration. A prospective study is ongoing to objectively quantify the benefits of this technique.

Association of obesity with postoperative outcomes after proctectomy

BackgroundPrior efforts evaluating obesity as a risk factor for postoperative complications following proctectomy have been limited by sample size and uniform outcome classification. MethodsThe ACS NSQIP was queried for patients with non-metastatic rectal adenocarcinoma who underwent elective proctectomy. After stratification by BMI classification, multivariable modeling was used to identify the effect of BMI class on adjusted risk of 30-day outcomes controlling for patient, procedure, and tumor factors. ResultsOf 2241 patients identified, 33.4% had a normal BMI, 33.5% were overweight, 21.1% were obese, and 12.0% were morbidly obese. Increased risk of superficial surgical site infection (SSI) was observed in obese (OR 2.42, 95%CI:[1.36–4.29]) and morbidly obese (OR 3.29, 95%CI:[1.77–6.11]) patients when compared to normal BMI. Morbid obesity was associated with increased risk of any complication (OR 1.44, 95%CI:[1.05–1.96]). BMI class was not associated with risk adjusted odds of anastomotic leak. ConclusionsMorbid obesity is independently associated with an increased composite odds risk of short-term morbidity following elective proctectomy for cancer primarily due to increased risk of superficial SSI.