Advanced Primary Rectal Cancer Research Articles

Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

A novel classification of posterior pelvic exenteration to assess prognosis in female patients with locally advanced primary rectal cancer: a retrospective cohort study from China PelvEx collaborative

PurposeSurgical techniques and the prognosis of posterior pelvic exenteration for locally advanced primary rectal cancer in female patients pose challenges that need to be addressed. Therefore, we investigated the short-term and survival outcomes of posterior pelvic exenteration in female patients using a novel Peking classification.MethodsWe retrospectively analysed a prospective database from China PelvEx Collaborative across three tertiary referral centres. A total of 172 patients who underwent combined resection for locally advanced primary rectal cancer were classified based on four subtypes (PPE-I [64/172], PPE-II [68/172], PPE-III [21/172], and PPE-IV [19/172]) according to the Peking classification; perioperative characteristics and short-term and oncological outcomes were analysed.ResultsDifferences were significant among the four groups regarding colorectal reconstruction (p < 0.001), perineal reconstruction (p < 0.001), in-hospital complications (p < 0.05), and urinary retention (p < 0.05). The R0 resection rates for PPE-I, PPE-II, PPE-III, and PPE-IV were 90.6%, 89.7%, 90.5%, and 89.5%, respectively. The 5-year overall survival rates of the PPE-I, PPE-II, PPE-III, and PPE-IV groups were 73.4%, 68.8%, 54.7%, and 37.3%, respectively. Correspondingly, their 5-year disease-free survival rates were 76.0%, 62.5%, 57.7%, and 43.1%, respectively. Notably, the PPE-IV group demonstrated the lowest 5-year overall survival rate (p < 0.001) and 5-year disease-free survival rate (p < 0.001).ConclusionThe Peking classification can aid in determining suitable surgical techniques and conducting prognostic assessments in female patients with locally advanced primary rectal cancer.

ASO Visual Abstract: Navigation-Assisted Surgery for Locally Advanced Primary and Recurrent Rectal Cancer.

ASO Visual Abstract: Navigation-Assisted Surgery for Locally Advanced Primary and Recurrent Rectal Cancer.

Transanal Minimally Invasive Surgical Approach to Total Pelvic Exenteration.

Total pelvic exenteration, a surgical procedure for patients with highly advanced primary and recurrent rectal cancer, is technically demanding. We report the utility of a transanal minimally invasive surgical approach to total pelvic exenteration. A 2-team approach with a laparoscopic transabdominal approach and transanal minimally invasive surgery was adopted. During the transabdominal approach in the pelvis, dissection was performed to remove the pelvic organs and visceral branches of the internal iliac vessels. The dissection goal via the transabdominal approach is the levator ani. During the transperineal approach, dissection is performed along the levator ani, and the tendinous arch of the levator ani is penetrated at the lateral side to achieve rendezvous between the 2 approaches. The levator ani is then dissected circumferentially, with identification of the internal pudendal vessels passing through the levator ani at the 4 o'clock and 8 o'clock positions, known as Alcock's canal. The anterior wall of Alcock's canal is formed by the coccygeus muscle and sacrospinous ligament, which are dissected by the transperineal approach to open Alcock's canal, thus obtaining a clear view of the internal pudendal vessels. On the anterior side, the urethra is divided with a laparoscopic linear stapler via the transperineal approach. Eight patients with rectal cancer underwent this procedure. The median (range) blood loss was 200 (120-1520) mL and operating time was 467 (321-833) minutes. Reoperation was performed in 1 internal hernia case; however, there were no mortalities, and there were no cases with severe complications or conversion to open surgery. When performing total pelvic exenteration, transanal minimally invasive surgery offers direct visualization behind the tumor from the anal side and shows the deep pelvic structures, including the retroperitoneal space of the pelvic sidewall.

Navigation-Assisted Surgery for Locally Advanced Primary and Recurrent Rectal Cancer

BackgroundIn some surgical disciplines, navigation-assisted surgery has become standard of care, but in rectal cancer, indications for navigation and the utility of different technologies remain undetermined.MethodsThe NAVI-LARRC prospective study (NCT 04512937; IDEAL Stage 2a) evaluated feasibility of navigation in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC). Included patients had advanced tumours with high risk of incomplete (R1/R2) resection, and navigation was considered likely to improve the probability of complete resection (R0). Tumours were classified according to pelvic compartmental involvement, as suggested by the Royal Marsden group. The BrainlabTM navigation platform was used for preoperative segmentation of tumour and pelvic anatomy, and for intraoperative navigation with optical tracking. R0 resection rates, surgeons’ experiences, and adherence to the preoperative resection plan were assessed.ResultsSeventeen patients with tumours involving the posterior/lateral compartments underwent navigation-assisted procedures. Fifteen patients required abdominosacral resection, and 3 had resection of the sciatic nerve. R0 resection was obtained in 6/8 (75%) LARC and 6/9 (69%) LRRC cases. Preoperative segmentation was time-consuming (median 3.5 h), but intraoperative navigation was accurate. Surgeons reported navigation to be feasible, and adherence to the resection plan was satisfactory.ConclusionsNavigation-assisted surgery using optical tracking was feasible. The preoperative planning was time-consuming, but intraoperative navigation was accurate and resulted in acceptable R0 resection rates. Selected patients are likely to benefit from navigation-assisted surgery.

Laparoscopic posterior pelvic exenteration is safe and feasible for locally advanced primary rectal cancer in female patients: a comparative study from China PelvEx collaborative.

Posterior pelvic exenteration (PPE) for locally advanced rectal cancer is a technical and challenging procedure. The safety and feasibility of laparoscopic PPE remain to be determined. This study aims to compare short-term and survival outcomes of laparoscopic PPE (LPPE) with open PPE (OPPE) in female patients. From January 2015 to December 2020, data from 105 female patients who underwent PPE at three institutions were retrospectively analyzed. The short-term and oncological outcomes between LPPE and OPPE were compared. A total of 54 cases with LPPE and 51 cases with OPPE were enrolled. The operative time (240 vs. 295min, p = 0.009), blood loss (100 vs. 300ml, p < 0.001), surgical site infection (SSI) rate (20.4% vs. 58.8%, p = 0.003), urinary retention rate (3.7% vs. 17.6%, p = 0.020), and postoperative hospital stay (10 vs. 13days, p = 0.009) were significantly lower in the LPPE group. The two groups showed no significant differences in the local recurrence rate (p = 0.296), 3-year overall survival (p = 0.129), or 3-year disease-free survival (p = 0.082). A higher CEA level (HR1.02, p = 0.002), poor tumor differentiation (HR3.05, p = 0.004), and (y)pT4b stage (HR2.35, p = 0.035) were independent risk factors for disease-free survival. LPPE is safe and feasible for locally advanced rectal cancers and shows lower operative time and blood loss, fewer SSI complications, and better preservation of bladder function without compromising oncological outcomes.

Surgical, survival and quality of life outcomes in over 1000 pelvic exenterations: lessons learned from a large Australian case series

To determine surgical, survival and quality of life outcomes across different tumour streams and lessons learned over 28 years. Consecutive patients undergoing pelvic exenteration at a single, high volume, referral hospital, between 1994 and 2022 were included. Patients were grouped according to their tumour type at presentation as follows, advanced primary rectal cancer, other advanced primary malignancy, locally recurrent rectal cancer, other locally recurrent malignancy and non-malignant indications. The main outcomes included, resection margins, postoperative morbidity, long-term overall survival, and quality of life outcomes. Non-parametric statistics and survival analyses were performed to compare outcomes between groups. Of the 1023 pelvic exenterations performed, 981 (95.9%) unique patients were included. Most patients underwent pelvic exenteration due to locally recurrent rectal cancer (N= 321, 32.7%) or advanced primary rectal cancer (N= 286, 29.2%). The rates of clear surgical margins (89.2%; P< 0.001) and 30-days mortality were higher in the advanced primary rectal cancer group (3.2%; P= 0.025). The 5-year overall survival rates were 66.3% in advanced primary rectal cancer and 44.6% in locally recurrent rectal cancer. Quality of life outcomes differed across groups at baseline, but generally had good trajectories thereafter. International benchmarking revelled excellent comparative outcomes. The results of this study demonstrate excellent outcomes overall, but significant differences in surgical, survival and quality of life outcomes across patients undergoing pelvic exenteration due to different tumour streams. The data reported in this manuscript can be utilized by other centres as benchmarking as well as proving both subjective and objective outcome details to support informed decision-making for patients.

An international, multicenter study of robotic versus open multi-visceral resections for locally advanced primary rectal cancer

An international, multicenter study of robotic versus open multi-visceral resections for locally advanced primary rectal cancer

SP9.2.1 Postoperative outcomes in patients undergoing Total Pelvic Clearance for locally advanced Primary and Recurrent Rectal Cancer: A Systematic Review to assess Perioperative Mortality, Rate of R0 Resection and 5Year Overall Mortality

Abstract Introduction The outcomes of complex surgical procedures such as Total pelvic clearance (TPC) have improved due to advances in technology, improvements in surgical technique and experience. Majority of Reviews include older studies diluting the benefits and outcomes. Secondly, very few studies mention all important outcomes in one leading to non-uniformity in reporting of data. Lastly, there was further need of updating the previous reviews, the last one published a decade earlier, hence, the review of Perioperative Mortality, rates of R0 resection and 5-year overall survival were carried out in patients undergoing TPC for primary or recurrent rectal cancer in a systematic manner. Methods Literature searches were performed in three databases: MEDLINE, PUBMED and Cochrane Library. Each study was evaluated with regards to its design and statistical methodology. The quality assessment of studies was carried out in this review as per the SIGN grading system. Publication bias was assessed by drawing funnel plots for each outcome. Each outcome was further analysed by creating Forrest plot using fixed effect model. Results A total of 1632 articles were identified through electronic databases. A total of 21 articles were finally included which met the inclusion and exclusion criteria. Out of 963 resections carried out, perioperative mortality was 3.4%. Overall R0 rection rates were 72.4%. Out of total 374 patients, overall, 5-year survival rate was 42%. Conclusion TPC is safe in experienced hands at specialist centres experienced in dealing with such cases with acceptable outcomes outlined above.

Updated systematic review of the approach to pelvic exenteration for locally advanced primary rectal cancer

ObjectivesTo review the evidence regarding surgical advances in the management of primary locally advanced rectal cancer. BackgroundThe management of rectal cancer has evolved significantly in recent decades, with improved (neo)adjuvant treatment strategies and enhanced perioperative protocols. Centralization of care for complex, advanced cases has enabled surgeons in these units to undertake more ambitious surgical procedures. MethodsA Pubmed, Ovid, Embase and Cochrane database search was conducted according to the predetermined search strategy. The review protocol was prospectively registered with PROSPERO (CRD42021245582). Results14 studies were identified which reported on the outcomes of 3,188 patients who underwent pelvic exenteration (PE) for primary rectal cancer. 50% of patients had neoadjuvant radiotherapy. 24.2% underwent flap reconstruction, 9.4% required a bony resection and 34 patients underwent a major vascular excision. 73.9% achieved R0 resection, with 33.1% experiencing a major complication. Median length of hospital stay ranged from 13 to 19 days. 1.6% of patients died within 30 days of their operation. Five-year overall survival (OS) rates ranged 29%–78%. LimitationsThe studies included in our review were mostly single-centre observational studies published prior to the introduction of modern neoadjuvant treatment regimens. It was not possible to perform a meta-analysis on the basis that most were non-randomized, non-comparative studies. ConclusionsPelvic exenteration offers patients with locally advanced rectal cancer the chance of long-term survival with acceptable levels of morbidity. Increased experience facilitates more radical procedures, with the introduction of new platforms and/or reconstructive options.

Pragmatic use of short-course radiotherapy, chemotherapy and surgery for stage IV rectal cancer with locally advanced or symptomatic primary tumours.

We assessed management of patients with de novo metastatic rectal cancer, referred for radiotherapy to the rectum, who were candidates for short-course radiotherapy (SCRT) and chemotherapy, followed by resection of all disease. We assessed surgical outcomes, overall survival (OS) and progression-free survival (PFS). Retrospective review of patients meeting criteria: (i) treatment with SCRT to rectum; (ii) locally advanced primary rectal cancer; and (iii) resectable distant metastases at diagnosis. Data were collected from charts, correspondence and electronic patient records. OS and PFS were calculated using the Kaplan-Meier method. Between 2016 and 2020, 48 patients with stage IV rectal cancer at diagnosis were treated with SCRT. Only 15 patients (31%) had resectable metastatic disease and were intended for SCRT (25 Gy/5#), then chemotherapy, followed by resection of all sites of disease and are included in our study. 12 of the 15 surgical candidates (80%) had rectal surgery as planned, and 11 of the 15 (73%) had resection of the rectal primary and all metastatic disease. One patient had a pathological complete response (pCR), and 50% of surgical patients had a Mandard TRG of 1 or 2. Median PFS and OS for the 15 surgical candidates were 12.6 and 25.2 months, respectively, with a median FU of 21.2 months. For this cohort of patients, our treatment paradigm is pragmatic and results in excellent pathological response. However, the effectiveness of this approach should be the subject of future prospective studies.

Outcomes of metastasectomy and pelvic exenteration for patients with metastatic advanced primary or recurrent rectal cancer.

ANZ Journal of SurgeryVolume 91, Issue 3 p. 231-232 PERSPECTIVE Outcomes of metastasectomy and pelvic exenteration for patients with metastatic advanced primary or recurrent rectal cancer Michelle Z. Chen MBBS (UNSW), MS (USYD), FRACS, Michelle Z. Chen MBBS (UNSW), MS (USYD), FRACS Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, AustraliaSearch for more papers by this authorKirk K. S. Austin BSc, MB, BCh, BAO, AFRCSI, FRACS, Kirk K. S. Austin BSc, MB, BCh, BAO, AFRCSI, FRACS Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, Australia Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, AustraliaSearch for more papers by this authorMichael J. Solomon MB, BCh, BAO MSc, DMedSc (USYD), DMed (NUI), FRACS, FRCSI, FASCRS, Michael J. Solomon MB, BCh, BAO MSc, DMedSc (USYD), DMed (NUI), FRACS, FRCSI, FASCRS professor.solomon@sydney.edu.au orcid.org/0000-0002-5602-6045 Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, Australia Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia The Institute of Academic Surgery at RPA, Sydney Local Health District, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, AustraliaSearch for more papers by this authorKilian G. M. Brown BBiomed, MBBS, MPhil, Kilian G. M. Brown BBiomed, MBBS, MPhil Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, Australia The Institute of Academic Surgery at RPA, Sydney Local Health District, Sydney, New South Wales, AustraliaSearch for more papers by this authorDaniel Steffens BPhty (Hons), PhD, Daniel Steffens BPhty (Hons), PhD orcid.org/0000-0002-9715-860X Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, Australia The Institute of Academic Surgery at RPA, Sydney Local Health District, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, AustraliaSearch for more papers by this author Michelle Z. Chen MBBS (UNSW), MS (USYD), FRACS, Michelle Z. Chen MBBS (UNSW), MS (USYD), FRACS Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, AustraliaSearch for more papers by this authorKirk K. S. Austin BSc, MB, BCh, BAO, AFRCSI, FRACS, Kirk K. S. Austin BSc, MB, BCh, BAO, AFRCSI, FRACS Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, Australia Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, AustraliaSearch for more papers by this authorMichael J. Solomon MB, BCh, BAO MSc, DMedSc (USYD), DMed (NUI), FRACS, FRCSI, FASCRS, Michael J. Solomon MB, BCh, BAO MSc, DMedSc (USYD), DMed (NUI), FRACS, FRCSI, FASCRS professor.solomon@sydney.edu.au orcid.org/0000-0002-5602-6045 Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, Australia Department of Colorectal Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia The Institute of Academic Surgery at RPA, Sydney Local Health District, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, AustraliaSearch for more papers by this authorKilian G. M. Brown BBiomed, MBBS, MPhil, Kilian G. M. Brown BBiomed, MBBS, MPhil Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, Australia The Institute of Academic Surgery at RPA, Sydney Local Health District, Sydney, New South Wales, AustraliaSearch for more papers by this authorDaniel Steffens BPhty (Hons), PhD, Daniel Steffens BPhty (Hons), PhD orcid.org/0000-0002-9715-860X Surgical Outcomes Research Centre, University of Sydney & Sydney Local Health District, Sydney, New South Wales, Australia The Institute of Academic Surgery at RPA, Sydney Local Health District, Sydney, New South Wales, Australia Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, AustraliaSearch for more papers by this author First published: 19 March 2021 https://doi.org/10.1111/ans.16294Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume91, Issue3March 2021Pages 231-232 RelatedInformation

Translational research of VOLTAGE-A: Efficacy predictors of preoperative chemoradiotherapy and consolidation nivolumab in patients with both microsatellite stable and microsatellite instability-high locally advanced rectal cancer.

100 Background: In VOLTAGE-A, chemoradiotherapy (CRT; 50.4Gy with capecitabine, 1,650mg/m2) followed by five cycles of consolidation nivolumab (nivo) (240mg q2 weeks) showed 30% pathological complete response [pCR; AJCC tumor regression grade (TRG) 0] and 38% major pathological responses (AJCC TRG 0-1) in patients with microsatellite stable (MSS) locally advanced primary rectal cancer (LARC). In addition, 60% pCR was observed in patients with microsatellite instability-high (MSI-H) LARC. In this study, we aimed to determine the predictive biomarkers for efficacy of sequential preoperative CRT and consolidation nivo. Methods: Serial tumor biopsies were performed at four time points:pre-CRT; post-CRT; post-3 cycles of nivo; and pre-surgery. We analyzed the immune status of the patients by flow cytometry using the collected tumor-infiltrating lymphocytes (TILs) dissociated from tumor samples. Whole exome and RNA sequencing analyses were conducted using the extracted DNA and RNA from tumor, respectively. The PD-L1 status of tumor samples was also evaluated by in vitro diagnostic immunohistochemistry staining. Results: Of the 38 MSS patients whose PD-L1 tumor proportion score (TPS) was analyzable in pre-CRT samples, the pCR rates were 67% (6/9) and 17% (5/29) in positive (≥1%) and negative PD-L1 status (p = 0.009), respectively. Among the 24 MSS patients whose samples were serially collected, the pCR rates according to CD8+ T cells/effector regulatory T cells (CD8/eTreg) ratio in TILs of pre-CRT samples ≥2.5 and &lt; 2.5 were 78% (7/9) and 13% (2/15), respectively (p = 0.003). The CD8/eTreg ratio in TILs was consistently high in patients with pCR during the study treatments. Ki-67 and PD-1 expression by CD8+ T cells in TILs was significantly high in pre-CRT samples from patients TRG 0-1. Conversely, in patients with TRG 2-3, CTLA-4 expression by both CD4+ T cells and CD8+ T cells in TILs was significantly high after five cycles of nivo, suggesting the potential resistance mechanisms of nivo monotherapy. Of the 21 MSS patients whose consensus molecular subtype (CMS) was analyzable, those with CMS1 and CMS3 tumors achieved 100% (2/2) and 60% (4/6) TRG 0-1, respectively. In contrast, patients with CMS2 and CMS4 tumors achieved 43% (3/7) and 29% (2/7) TRG 0-1, respectively. The tumor mutational burden (TMB) of pre-CRT samples in five MSI-H patients was higher than that in the 24 MSS patients (median: 13.2 vs. 0.99 mutation/Mbp, p &lt; 0.0001). Among MSS patients, TMB was higher in patients with TRG 0-1 than in patients with TRG 2-3 (median: 1.45 vs. 0.84 mutation/Mbp, p = 0.016). Conclusions: Positive PD-L1 TPS; high CD8/eTreg ratio; Ki-67, PD-1, and CTLA-4 expression by CD8+ T cells in TILs; CMS 1 or 3; and high TMB can be good predictors of efficacy of preoperative CRT followed by nivo. Clinical trial information: NCT02948348.

Total Pelvic Exenteration, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy for Rectal Cancer with Associate Peritoneal Metastases: Surgical Strategies to Optimize Safety.

Simple SummaryCytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment for patients with peritoneal carcinomatosis. Pelvic exenteration is an established treatment option for locally advanced pelvic malignancy. Based on the argument that high-risk complications arise from each procedure, the majority of researchers do not recommend performing a CRS/HIPEC with pelvis exenteration. Herein, we critically analyzed the data from 16 patients treated by these two procedures for 15 rectal and one appendiceal adenocarcinomas. Clear resection (R0) margins were achieved in 81.2% of cases. The median hospital stay was 46 days (26–129), and nine patients (56.2%) experienced severe complications that led to death in two cases (12.5%). Survival rates were not clarified, since the follow-up is ongoing. Pelvis exenteration associated with CRS/HIPEC may be a reasonable procedure in selected patients at expert centers. Pelvic involvement should not be considered a definitive contraindication for CRS/HIPEC if a R0 resection could be achieved. However, the morbidity and the mortality are high with this combination of treatment, and further research is needed to assess the oncologic benefit and quality of life before such a radical approach can be recommended.Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for patients with peritoneal carcinomatosis. Total pelvic exenteration (TPE) is an established treatment option for locally advanced pelvic malignancy. These two procedures have high mortality and morbidity, and therefore, their combination is not currently recommended. Herein, we reported our experience on TPE associated with CRS/HIPEC with a critical analysis for rectal cancer with associate peritoneal metastases. Methods: From March 2006 to August 2020, 319 patients underwent a CRS/HIPEC in our hospital. Among them, 16 (12 men and four women) underwent an associated TPE. The primary endpoints were perioperative morbidity and mortality. Results: There was locally recurrent rectal cancer in nine cases, six locally advanced primary rectal cancer, and a recurrent appendiceal adenocarcinoma. The median Peritoneal Cancer Index (PCI) was 8. (4–16). Mean duration of the surgical procedure was 596 min (420–840). Complete cytoreduction (CC0) was achieved in all patients, while clear resection (R0) margins on the resected pelvic organs were achieved in 81.2% of cases. The median hospital stay was 46 days (26–129), and nine patients (56.2%) experienced severe complications (grade III to V) that led to death in two cases (12.5%). The total reoperation rate for patients was 6/16 (37.5%) and 3/16 (18.75%) with percutaneous radiological-guided drainage. Conclusions: In summary, TPE/extended TPE (ETPE) associated with CRS/HIPEC may be a reasonable procedure in selected patients at expert centers. Pelvic involvement should not be considered a definitive contraindication for CRS/HIPEC in patients with resectable peritoneal surface diseases if a R0 resection could be achieved on all sites. However, the morbidity and the mortality are high with this combination of treatment, and further research is needed to assess the oncologic benefit and quality of life before such a radical approach can be recommended.

Pelvic exenteration for locally advanced and local recurrent primary rectal cancer: a 5 years Asian retrospective cohort study and lessons to learn

Background: Locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC) were deemed incurable, but with surgical advancement, pelvic exenteration has emerged as a curative option. Although colorectal cancer cases are common, pelvic exenterations are limited to several centres in Malaysia. The study aimed to determine the outcomes of pelvic exenteration from the centre in terms of complete resection, local recurrence rate, mortality rate and complications rate.Methods: Retrospective data collection was done for pelvic exenteration surgeries of LARC and LRRC from year 2014 till 2018 in a Malaysian tertiary referral centre. Demographic data, types of pelvic exenteration, postoperative complications, postoperative histopathology for complete resection (R0) and local recurrence were collected from the hospital medical records.Results: From 2014 till 2018, 51 cases of pelvic exenteration were done, with a mean age of 55.8±12.4 years and predominance of male gender (55%). Thirty-four cases (66.7%) completed the exenteration. A mere 24 cases (47.1%) had complete preoperative imaging of computed tomography (CT scan), pelvic magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET/CT) scan. R0 resection was achieved in 23 cases (67.6%). Complications were found in 44.8% of patients including anastomotic leak, collection, surgical site infection or cardiac/lung complications. The 30-days postoperative mortality rate is 3.9%. The six-months local recurrence rate was 5.8% and one-year local recurrence rate was 7.8%.Conclusion: Pelvic MRI and PET-CT scan is suggested to be compulsory for all pelvic exenteration candidates to ensure a good outcome. Multidisciplinary team approach is needed preoperatively to discuss the feasibility of pelvic exenteration to optimise the outcomes of this surgery.

Pelvic exenteration combined with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for advanced primary or recurrent colorectal cancer with peritoneal metastases.

The aim was to report early outcomes of six patients who underwent combined pelvic exenteration (PE), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced or recurrent colorectal cancer with colorectal peritoneal metastases at a single centre. The literature contains limited data on the safety and oncological outcomes of patients who undergo this combined procedure. Six patients who underwent combined PE, CRS and HIPEC at Royal Prince Alfred Hospital, Sydney, between January 2017 and February 2020 were identified and included. Data were extracted from prospectively maintained databases. Three patients underwent surgery for advanced primary rectal cancer, while two patients had recurrent sigmoid cancer and one had recurrent rectal cancer. All patients had synchronous peritoneal metastases. Two patients required total PE and two patients had a central (bladder-sparing) PE. The median peritoneal carcinomatosis index was 6 (range 3-12) and all patients underwent a complete cytoreduction. The median operating time was 702min (range 485-900) and the median blood loss was 1650ml (range 700-12,000). The median length of intensive care unit and hospital stay was 4.5 and 25days, respectively. There was no inpatient, 30-day or 90-day mortality. Three patients (50%) experienced a major (Clavien-Dindo III/IV) complication. At a median follow-up of 11.5months (range 2-18months), two patients died with recurrent disease, one patient was alive with recurrence, while three patients remain alive and disease-free. Of the three patients who developed recurrent disease, one had isolated pelvic recurrence, one had pelvic and peritoneal recurrences and one had bone metastases. Early results from this initial experience with simultaneous PE, CRS and HIPEC suggest that this combined procedure is safe and feasible; however, the long-term oncological and quality of life outcomes require further investigation.

Surgical outcomes of hybrid hand-assisted laparoscopic pelvic exenteration for locally advanced rectal cancer: Initial experience.

Hybrid hand-assisted laparoscopic surgery (HALS) combines better visualization of laparoscopic surgery with the advantages of open surgery. The aim of this study was to describe important technical considerations of HALS and to assess the feasibility of hybrid HALS pelvic exenteration (PE) for primary advanced rectal cancer. From May 2012 to August 2018, we retrospectively analyzed 11 patients who underwent PE for primary advanced rectal cancer (< 10 cm from the anal verge). Patients were divided into the open PE group (n = 5) and the hybrid HALS PE group (n = 6). There was no significant difference in patient characteristics between the two groups, and all included patients were male. Tumor invasion to adjacent organs was mostly anterior invasion. In addition, four patients (66%) in the hybrid HALS PE group and two (40%) in the open PE group received neoadjuvant therapy (P = .3). Compared to open surgery, hybrid HALS has the advantages of less bleeding and less invasion, and can achieve the same results in the short-term. It was a reasonable procedure which was easy and safe dissection of internal iliac vessels and dorsal vein complex. Thus, hybrid HALS may become a useful approach for PE.

Association of Image-Guided Navigation With Complete Resection Rate in Patients With Locally Advanced Primary and Recurrent Rectal Cancer

The percentage of tumor-positive surgical resection margin rates in patients treated for locally advanced primary or recurrent rectal cancer is high. Image-guided navigation may improve complete resection rates. To ascertain whether image-guided navigation during rectal cancer resection improves complete resection rates compared with surgical procedures without navigation. This prospective single-center nonrandomized controlled trial was conducted at the Netherlands Cancer Institute-Antoni van Leeuwenhoek in Amsterdam, the Netherlands. The prospective or navigation cohort included adult patients with locally advanced primary or recurrent rectal cancer who underwent resection with image-guided navigation between February 1, 2016, and September 30, 2019, at the tertiary referral hospital. Clinical results of this cohort were compared with results of the historical cohort, which was composed of adult patients who received rectal cancer resection without image-guided navigation between January 1, 2009, and December 31, 2015. Rectal cancer resection with image-guided navigation. The primary end point was the complete resection rate, measured by the amount of tumor-negative resection margin rates. Secondary outcomes were safety and usability of the system. Safety was evaluated by the number of navigation system-associated surgical adverse events. Usability was assessed from responses to a questionnaire completed by the participating surgeons after each procedure. In total, 33 patients with locally advanced or recurrent rectal cancer were included (23 men [69.7%]; median [interquartile range] age at start of treatment, 61 [55.0-69.0] years). With image-guided navigation, a radical resection (R0) was achieved in 13 of 14 patients (92.9%; 95% CI, 66.1%-99.8%) after primary resection of locally advanced tumors and in 15 of 19 patients (78.9%; 95% CI, 54.4%-94.0%) after resection of recurrent rectal cancer. No navigation system-associated complications occurred before or during surgical procedures. In the historical cohort, 142 patients who underwent resection without image-guided navigation were included (95 men [66.9%]; median [interquartile range] age at start of treatment, 64 [55.0-70.0] years). In these patients, an R0 resection was accomplished in 85 of 101 patients (84.2%) with locally advanced rectal cancer and in 20 of 41 patients (48.8%) with recurrent rectal cancer. A significant difference was found between the navigation and historical cohorts after recurrent rectal cancer resection (21.1% vs 51.2%; P = .047). For locally advanced primary tumor resection, the difference was not significant (7.1% vs 15.8%; P = .69). Surgeons stated in completed questionnaires that the navigation system improved decisiveness and helped with tumor localization. Findings of this study suggest that image-guided navigation used during rectal cancer resection is safe and intuitive and may improve tumor-free resection margin rates in recurrent rectal cancer. Netherlands Trial Register Identifier: NTR7184.

Clinical Advantage of Image-Guided Navigation for Locally Advanced Primary and Recurrent Rectal Cancer

Clinical Advantage of Image-Guided Navigation for Locally Advanced Primary and Recurrent Rectal Cancer

Translational research of voltage-A1: Efficacy predictors of preoperative chemoradiotherapy and subsequent nivolumab monotherapy in patients with microsatellite-stable locally advanced rectal cancer.

4073 Background: In VOLTAGE-A1, after 5 cycles of nivolumab (240 mg q2 weeks) plus radical surgery following chemoradiotherapy (CRT; 50.4 Gy with capecitabine 1,650 mg/m2), a major pathologic response is observed in 38% (AJCC tumor regression grade 0-1) of 37 patients with microsatellite-stable locally advanced primary rectal cancer. Here, biomarkers for predicting the efficacy of this treatment were investigated. Methods: Serial tumor biopsies and blood collections were performed at 4 time points; before CRT, after CRT, after 3 cycles of nivolumab, and before surgery. Tumor-infiltrating lymphocytes (TILs) and DNA/RNA were extracted from tumor samples, and peripheral blood mononuclear cells (PBMCs) were extracted from blood samples. We analyzed the immune status of the patients by flow cytometry using the collected TILs and PBMCs. Whole exome and RNA sequencing analyses were conducted using the extracted DNA and RNA, respectively. The PD-L1 status of tumor samples was also evaluated by in vitro diagnostic immunohistochemistry staining. Results: Among the 24 patients whose samples were serially collected, 11 (46%) were AJCC grade 0-1 and 13 were 2-3. Before CRT, effector regulatory T (eTreg) cells in TILs were higher in patients with AJCC grade 2-3, and both the CD8+ T cell/eTreg cell ratio in TILs and PD-L1-positive tumor cells (≥1%) were higher in patients with AJCC grade 0-1 (p = 0.047, p = 0.083, respectively). Ki67 expression by CD8+ T cells in TILs was higher before CRT in patients with AJCC grade 0-1 (p = 0.037) and increased after CRT in all patients. Patients with consensus molecular subtype (CMS) 1 and CMS3 achieved AJCC grade 0-1 at rates of 100% (2/2) and 60% (4/6), respectively. In contrast, patients with CMS2 and CMS4 achieved AJCC grade 0-1 at rates of 43% (3/7) and 29% (2/7), respectively. The tumor mutation burden of pre-CRT samples was significantly higher in patients with AJCC grade 0-1 (median 1.45/MB) than in patients with AJCC grade 2-3 (0.84/MB) (p = 0.016). Conclusions: A higher CD8+ T cell/eTreg cell ratio, PD-L1-positive, Ki67 expression by CD8+ T cells in TILs, CMS1 or 3, and higher tumor mutation burden are good predictors of the efficacy of the sequential combination of CRT and nivolumab. Further results will be reported in the meeting. Clinical trial information: NCT02948348 .