Locally Advanced Colon Cancer Research Articles

Preoperative Strategies for Locally Advanced Colon Cancer.

Neoadjuvant chemotherapy is safe for patients with locally advanced colon cancer (LACC). The FOxTROT trial demonstrated a reduction in residual and recurrent cancer at 2 years with neoadjuvant chemotherapy for patients with cT3-4 LACC. Preoperative chemotherapy should be avoided, if possible, for patients with dMMR LACC, as over 50% of dMMR cancers have no pathologic response. Early universal testing of MMR status is critical to selecting the appropriate neoadjuvant therapy. Concerns about CT staging of LACC have limited uptake of neoadjuvant chemotherapy, as approximately 25% of patients with cT3-T4 cancer on CT have low-risk stage II disease. Development of CT criteria for malignant nodes should reduce the risk of over-staging. A multidisciplinary approach is needed to identify patients for neoadjuvant therapy. Neoadjuvant immunotherapy is safe and results in dramatic pathologic responses in patients with dMMR LACC. Longer follow-up is needed to determine if the exceptionally high pathologic response rates observed will translate into long-term remission. Remarkably, neoadjuvant immunotherapy has been found to cause major pathologic responses in a subset of patients with pMMR LACC, indicating the potential to cure more patients with this common cancer. Patients with cT4 LACC, whether stage II or III, have a substantial risk of recurrence despite adjuvant fluoropyrimidine plus oxaliplatin chemotherapy. We recommend neoadjuvant systemic therapy for all patients with cT4b LACC (dMMR and pMMR). Features of T4b disease are routinely reported by radiology. We use three cycles of FOLFOX chemotherapy for patients with cT4b pMMR LACC, due to the high rate of compliance and improvement in residual and recurrent disease. Patients with cT4b dMMR LACC should receive neoadjuvant immunotherapy, if there are no contraindications. Clinical trials of neoadjuvant therapy for LACC are of great interest and should provide training for radiologists to identify eligible patients. Results are anticipated from multiple ongoing trials of neoadjuvant chemotherapy, immunotherapy, and targeted therapy for pMMR LACC and immunotherapy for dMMR LACC.

Study protocol of short-course radiotherapy combined with CAPOX and PD-1 inhibitor for locally advanced colon cancer: a randomised, prospective, multicentre, phase II trial (TORCH-C)

IntroductionThe preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1...

A randomized phase II study comparing preoperative mFOLFOX6 versus FOLFOXIRI for locally advanced colon cancer: JCOG2006.

The prognosis of locally advanced colon cancer (LACC) with surgical resection followed only by adjuvant chemotherapyis poor. Preoperative chemotherapy for LACC patients with risk factorssuch as cT4bN+ or cT3-4aN2-3has attracted attention. Here, the authorsdescribe the rationale and design of JCOG2006, a randomized phase II study comparing preoperative chemotherapy with mFOLFOX6 versus FOLFOXIRI for LACC. Their efficacy and safety areevaluatedand a determination ofwhich is the more promising treatment will beconducted in a subsequent phase III trial. A total of 86patients will be accrued from 44 institutions over 2years. The primary end point is the proportion of patientswith a Tumor Regression Score of 0-2, and secondary end points include overall survival, response rateand adverse events. Clinical Trial Registration: jRCTs031210365 (https://jrct.niph.go.jp/).

The FOxTROT platform: Clinical trials and exploratory research for personalization of neoadjuvant (NA) therapy in locally advanced colon cancer (LACC)—ISRCTN83842641.

TPS3636 Background: The FOxTROT1 trial demonstrated a significant reduction in 2-year (yr) recurrence with 6 weeks (wks) of oxaliplatin and fluoropyrimidine (OxFp) NA chemotherapy (NAC) in patients (pts) with LACC, establishing NAC as a new therapeutic option. The ongoing FOxTROT platform will refine and personalize NA therapy in LACC. FOxTROT2 is testing NAC in older pts and those with frailty, who are poorly represented in clinical trials. FOxTROT3 is assessing intensified NAC with modified FOLFOXIRI (mFOLFOXIRI; 5-fluorouracil, oxaliplatin, irinotecan) in fit pts. The FOxTROT platform will also test targeted treatments with established safety and efficacy in defined molecular subgroups. FOxTROT4 is investigating the efficacy and safety of NA encorafenib and cetuximab in BRAF-mutant pMMR LACC. Other arms in setup are shown in Table. Methods: FOxTROT platform trials are international, multicenter, open-label, phase II/III RCTs. Pts with resectable, cT3-4 N0-2 M0, biopsy-proven colon adenocarcinoma are eligible for recruitment. Pts whose age or frailty precludes mFOLFOXIRI can be considered for FOxTROT2. Pts suitable for mFOLFOXIRI can be considered for FOxTROT3. BRAF-mutant pMMR pts can be considered for FOxTROT4. Pts are randomized 2:1 between intervention and control arms. FOxTROT2 randomizes between 6 wks OxFp NAC (choice of 100% or 80% dose) vs proceeding straight to surgery. Adjuvant chemotherapy (AC) is per physician choice. Primary outcome is 3-yr DFS. 759 pts will be recruited over 5 yrs. FOxTROT3: 6 wks mFOLFOXIRI NAC vs 6 wks OxFp NAC. All pts receive AC but physicians may de-escalate mFOLFOXIRI to OxFp. Hierarchical co-primary endpoints: tumor regression grade (TRG) (blinded central assessment) and 3-yr DFS. 873 pts over 5 yrs. FOxTROT4: 6 wks NA encorafenib and cetuximab vs 6 wks OxFp NAC. AC is per physician choice. Primary outcome: TRG. 45 pts over 3 yrs. Secondary outcomes include: histopathological endpoints, downstaging, minimal residual disease by ctDNA, safety, toxicity, OS, surgical outcomes and patient-reported outcomes; and DFS in FOxTROT4. The FOxTROT platform opened 7th Feb 2022, funded by Yorkshire Cancer Research. At submission, 50 pts had been randomized at 23 centers. Trial design and management is conducted in partnership with patient representatives. A program of translational and radiomics research is running in parallel. International recruitment in France and India will commence in 2023 with additional international partners joining from 2024. Clinical trial information: ISRCTN83842641 . [Table: see text]

Clinical Evidence for the Benefits of Neoadjuvant Chemotherapy and Immunotherapy in Colon Cancer: A Concise Review.

Neoadjuvant chemotherapy (NAC) has long been considered technically difficult in locally advanced colon cancer (LACC). However, the introduction of oxaliplatin-based regimens led to a growing interest in NAC for patients with LACC. Several cohort studies showed that NAC was safe and reduced the rate of incomplete resection in patients with LACC. This was followed by the pivotal phase III FOxTROT trials, which showed significant benefits of NAC in this population. However, in patients with deficient mismatch repair (dMMR), the response to a neoadjuvant fluoropyrimidine regimen may be poor, limiting the benefit of NAC in this subset of patients. Neoadjuvant immunotherapy is a potential alternative for NAC in LACC patients with dMMR. In this concise review, we present the published clinical evidence evaluating the efficacy and safety of NAC and/or neoadjuvant immunotherapy in patients with LACC. Overall, the evidence suggests that NAC can be associated with significant downstaging and tumor regression, which facilitate surgical resection. However, the impact of NAC on long-term survival is still under investigation. Despite the promising results of NAC in LACC, several concerns still exist that necessitate further evidence. On the other hand, LACC patients with dMMR can benefit from neoadjuvant immunotherapy; however, further trials are still needed to confirm its effectiveness, as well as biomarkers that can predict response.

Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer

Despite the implementation of global screening programs, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. More than 10% of patients with colon cancer are diagnosed as having locally advanced disease with a relatively poor five-year survival rate. Locally advanced colon cancer (LACC) presents surgical challenges to R0 resection. The advantages and disadvantages of preoperative radiotherapy for LACC remain undetermined. Although several reliable novel biomarkers have been proposed for the prediction and prognosis of CRC, few studies have focused solely on the treatment of LACC. This comprehensive review highlights the role of predictive biomarkers for treatment and postoperative oncological outcomes for patients with LACC. Moreover, this review discusses emerging needs and approaches for the discovery of biomarkers that can facilitate the development of new therapeutic targets and surveillance of patients with LACC.

Recurrence After Colectomy for Locally Advanced Colon Cancer: Experience from a Developing Country

Risk factors for disease recurrence following curative resection for locally advanced colon cancer (LACC) remain unclear as conflicting results have been reported in the literature. The aim of this study was to examine these factors in the setting of developing country’s health care system affected by limited accessibility to the multimodal cancer treatment. Patients who had undergone curative colon resection for LACC between 2004 and 2018 were included. Data were obtained from a prospectively maintained database. Factors associated with disease recurrence, types of recurrence and recurrence-free survival were studied. A total of 118 patients with LACC were operated within the study period. Median follow-up was 36 (2-147) months. Adjuvant therapy was used in 41 (34.7%) patients and 62 (52.5%) were diagnosed with recurrence. In the multivariable analysis, disease recurrence was associated with tumor and nodal stages, as well as with the lymph node yield. Local recurrence, distant metastases, and peritoneal carcinomatosis were observed in 8 (6.8%), 30 (25.4%), and 24 (20.3%) patients, respectively. Early recurrence was diagnosed in 27 (22.9%) cases with peritoneal carcinomatosis being its most common type. Preoperative serum CA 19–9 levels, tumor, and nodal stages were linked to recurrence-free survival in the univariable analysis. Only tumor stage remained such in the multivariable model. Our findings suggest that lymph node yield, tumor, and nodal stages are associated with recurrence following curative resection for LACC.

Prognostic value of final pathological stage in colon adenocarcinoma after neoadjuvant chemotherapy: A propensity score-matched study.

Neoadjuvant chemotherapy (NAC) could improve local tumor control of locally advanced colon cancer (LACC), but the prognostic value of yp stage in colon cancer remains unknown. Here, we aimed to ascertain yp stage as an indicator for LACC prognosis after NAC. The data of patients diagnosed with colon adenocarcinoma between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results database. After 1:2 propensity score matching, cancer-specific survival (CSS) and overall survival (OS) were compared between the NAC and Non-NAC groups of different stage classifications. The correlation between clinical and pathological factors and CSS was identified. A total of 49, 149, and 81 matched pairs of stage 0-I, II, and III patients, respectively, were generated for analysis. For stage 0-I (p = 0.011) and III (p = 0.015), only CSS in the NAC groups were inferior. Receiving NAC was an independent prognostic risk factor for patients with stage 0-I (hazard ratio, 7.70; 95% confidence interval, 1.820-32.5; p = 0.006) and stage III (hazard ratio, 1.73; 95% confidence interval, 1.11-2.68; p = 0.015). The CSS was poorer among LACC patients who underwent NAC than among those who did not. The yp stage of colon cancer after NAC has distinctive significance, which may contribute to predicting the prognosis and guiding the treatment of LACC patients after NAC.

Neoadjuvant Chemoradiotherapy Significantly Improved R0 Resection Rate in Unresectable Locally Advanced Colon Cancer: The Initial Analysis from the Randomized Controlled Phase 3 Trial

<h3>Purpose/Objective(s)</h3> Neoadjuvant chemotherapy (NACT) is often used for tumor downstaging in locally advanced colon cancer (LACC) and improves the R0 resection rate. Based on previous findings, we hypothesized that neoadjuvant chemoradiotherapy (NACRT) might bring a higher R0 resection rate and survival benefit to patients with unresectable LACC. Our perspective study aimed at comparing NACRT versus NACT for unresectable LACC to confirm our hypothesis. <h3>Materials/Methods</h3> We performed the world's first randomized controlled phase 3 trial on NACRT for LACC at our institution. Eligible patients had newly diagnosed unresectable LACC. We randomly allocated patients open-label to the NACT group (control group) or the NACRT group (research group). Chemotherapy regimen was XELOX (oxaliplatin 100-130mg/m2, iv drip, d1, every 3 weeks; capecitabine 1,000mg/m2, bid, d1-d14, every 3 weeks). Patients allocated radiotherapy received a daily irradiation schedule (GTV:50Gy/25F/5W, CTV:45Gy/25F/5W). Surgery scheduled 6–8 weeks after radiotherapy and adjuvant chemotherapy were given if patients transformed into resectable LACC. <h3>Results</h3> Between July 2019 and July 2021, 49 patients with unresectable LACC underwent randomization and 45 patients (4 excluded) were analyzed for efficacy finally. There were 23, 6, 8, 7 and 1 patients with primary tumor location at sigmoid colon, descending colon, transverse colon, ascending colon and ileocecus. The median follow-up time was 20.7 months. Allocated groups were balanced, with 25 patients receiving NACRT and 20 patients receiving NACT. Twenty-one (84%) patients in the NACRT group transformed to resectable LACC after planned neoadjuvant treatment and received surgery while there were only 5 (20%) patients in the NACT group. Compared to NACT, the use of NACRT improved the R0 resection rate (80% vs 20%) significantly. The 2-year progression-free survival is 72.2% in the NACRT group and 37.4% in the NACT group (p=0·029). The 2-year overall survival is 95.5% in the NACRT group and 73.1% in the NACT group (p=0·035). No increasing toxicities and postsurgical complications were observed from the NACRT group compared with the NACT group. The trial is terminated since the R0 resection rate and survival between the two groups had shown a significant difference. Also, the patients' MMR/MSI status was not considered at the beginning of the study design. <h3>Conclusion</h3> Based on neoadjuvant chemotherapy, the addition of radiotherapy provided a higher R0 resection rate, longer progression-free survival and even might improve overall survival for patients with unresectable LACC. We concluded that this approach is safe, feasible and might associate with a better survival benefit. We are designing new clinical studies to further demonstrate the value of NACRT in LACC. This trial is registered with ClinicalTrials.gov, number NCT03970694.

Efficacy and Safety of Neoadjuvant Chemotherapy Combined with Adjuvant Chemotherapy for Locally Advanced Colon Cancer: A Propensity Score-Matching Analysis.

Background and Objectives: Increasing evidence supports the use of neoadjuvant chemotherapy (NAC) for locally advanced colon cancer (LACC). However, its effectiveness remains controversial. This study explored the safety and efficacy of NAC combined with laparoscopic radical colorectal cancer surgery and adjuvant chemotherapy (AC) for LACC. Materials and Methods: We retrospectively analyzed 444 patients diagnosed with LACC (cT4 or cT3, with ≥5 mm invasion beyond the muscularis propria) in our hospital between 2012 and 2015. Propensity score matching (PSM; 1:2) was performed to compare patients treated with NAC and those treated with adjuvant chemotherapy (AC). Results: Overall, 42 patients treated with NAC were compared with 402 patients who received only AC. After PSM, 42 patients in the NAC group were compared with 84 patients in the control group, with no significant differences in the baseline characteristics between groups. The pathological tumor sizes in the NAC group were significantly smaller than those in the AC group (3.1 ± 2.1 cm vs. 5.8 ± 2.5 cm). Patients in the NAC group had a significantly lower T stage than those in the AC group (p &lt; 0.001). After neoadjuvant chemotherapy, a significant response was observed in four (9.6%) patients, with two (4.8%) showing a complete response. The 5-year overall survival rates (88.1% vs. 77.8%, p = 0.206) and 5-year disease-free survival rates (75.1% vs. 64.2%, p = 0.111) did not differ between the groups. However, the 5-year cumulative rate of distant recurrence was significantly lower in the NAC than in the AC group (9.6% vs. 29.9%, p = 0.022). Conclusions: NAC, combined with AC, could downstage primary tumors of LACC and seems safe and acceptable for patients with LACC, with a similar long-term survival between the two treatments.

Efficacy and Safety of Neoadjuvant Monoimmunotherapy With PD-1Inhibitor for dMMR/MSI⁃H Locally Advanced Colorectal Cancer: A Single-Center Real-World Study.

ObjectiveTo explore the efficacy and safety of single-agent programmed cell death protein-1 (PD-1) inhibitor in the neoadjuvant treatment of patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) locally advanced colorectal cancer (LACRC) through single-center large⁃sample analysis based on real⁃world data in China.MethodsThis study was a retrospective, single-center, case series study. 33 colorectal cancer (CRC) patients with clinical stage of T3~4N0~2M0 treated in Yunnan Cancer Hospital from June 2019 to June 2021 were analyzed retrospectively. Among them, 32 patients were dMMR or MSI-H or both dMMR and MSI-H, and one patient was both dMMR and microsatellite stability (MSS) (excluded in the final analysis). All 32 patients received neoadjuvant immunotherapy (nIT) with single-agent PD⁃1 inhibitor.ResultsAmong the 32 patients, 8 (25%) were locally advanced rectal cancer (LARC) and 24 (75%) were locally advanced colon cancer (LACC); 4 (12.55%) were stage II and 28 (87.5%) were stage III. The median number of cycles of 32 patients with dMMR/MSI-H LACRC receiving nIT with single-agent PD-1 blockade was 6 (4~10), and the median number of cycles to achieve partial response (PR) was 3 (2~4). Among them, three LARC patients achieved clinical complete response (cCR) and adopted the watch-and-wait (W&W) strategy. The objective response rate (ORR) of the other 29 patients with radical surgery was 100% (29/29), the pathological response rate was 100% (29/29), the rate of major pathological response (MPR) was 86.2% (25/29), and the rate of pathological complete response (pCR) was 75.9% (22/29). The incidence of immune-related adverse events (irAEs) in 32 patients during nIT was 37.5% (12/32), while the incidence of irAEs in 22 patients with operation during adjuvant immunotherapy was 27.3% (6/22), all of which were grade 1~2. No grade 3 or above irAEs were occured. The median time from the last nIT to surgery was 27 (16~42) days. There were no delayed radical resection due to irAEs in these patients. All 29 patients achieved R0 resection. The incidence of surgical-related adverse events (srAEs) in perioperative period was 10.3% (3/29).ConclusionsNeoadjuvant monoimmunotherapy with PD-1 inhibitor has favorable ORR and pCR rate, and relatively low incidences of irAEs and srAEs for patients with dMMR/MSI-H LACRC, suggesting that this nIT regimen of single-agent PD-1 inhibitor is significantly effective and sufficiently safe.

Neoadjuvant chemotherapy in patients undergoing colonic resection for locally advanced nonmetastatic colon cancer: Anationwide propensity score matched cohort study.

Neoadjuvant chemotherapy (NCT) for nonmetastatic colon cancer is not routinely used, and is currently only recommended as a treatment option for a subgroup of patients with T4b colon cancers in clinical guidelines. However, NCT may cause downstaging of the tumour, increase resectability, eradicate micrometastases and thereby improve long-term outcomes for patients with nonmetastatic colon cancer. The aim of this study was to investigate the short-term postoperative outcomes in a nationwide cohort of patients with locally advanced colon cancer (LACC) receiving NCT. Using the Danish Colorectal Cancer Group Database, data were retrieved on patients diagnosed with LACC (defined as clinical T3 with extramural tumour invasion >5mm or T4) and treated with resection with a curative intent between 2015 and 2019. Propensity score matching (PSM) in a 1:1 ratio was performed to compare short-term surgical and oncological outcomes in patients receiving NCT with patients operated on without receiving NCT. A total of 179 LACC patients were treated with NCT and 1131 were not. After PSM, 145 patients remained in each group. We found no significant differences in any short-term postoperative outcomes between the two groups. We found significant differences in favour of NCT regarding radicality and pathological N category [86% vs. 81% R0 (P=0.029) and 51% vs. 46% pN0 (P=0.017), respectively]. Neoadjuvant chemotherapy for LACC does not result in worse short-term postoperative outcomes and may increase the R0 rate as well as node-negative disease. Results on long-term benefits including survival are awaited from several ongoing randomized controlled trials.

Post-operative outcomes in patients with locally advanced colon cancer: a comparison of operative approach.

Surgeons may choose an open approach to locally advanced colon cancer (LACC) because of the elevated conversion rate (minimally invasive to open) in these patients (resulting in part from a judgment of the technical feasibility of a minimally invasive approach). Poorer outcomes have been suggested in those requiring conversion from a minimal access to an open approach; however, the influence of conversion has not been studied in LACC. We sought to compare perioperative outcomes in patients with T4aN2 colon cancer undergoing minimally invasive surgery (MIS), planned open (PO), and converted (CN) procedures to evaluate the influence of conversion in this subgroup. A retrospective cohort study was conducted using the NSQIP database. Patients with T4aN2 colon cancer undergoing elective resection were included; rectal/unknown tumor location, and T4b disease were excluded (to ensure homogeneity in surgical management). Patients were divided into cohorts based on approach: PO, MIS, and CN. Summary statistics were compared between groups. Multivariable analysis was conducted for mortality and morbidity outcomes. 1286 cases were included (313 PO, 842 MIS, 131 CN); 10.2% underwent conversion. Those undergoing MIS had a shorter length of stay than those undergoing PO or CN (p < 0.0001). On univariable analysis, CN resulted in increased rates of any complication (p < 0.0001). CN also had a greater rate of anastomotic leak (p = 0.0046) and death (p = 0.05). On multivariable analysis, significant predictors of any complication included age, ASA class, M stage, and approach; however, CN did not increase the risk of complication compared with MIS, whereas PO nearly doubled the risk of complication (OR = 1.98, p = 0.0083). The only significant predictor of mortality on multivariable analysis was age (HR = 1.09, p = 0.0002)-approach was not associated with mortality. PO confers the greatest risk of suffering any complication. Surgical approach was not associated with death. Results of our study challenge the notion that conversion is associated with the worst perioperative outcomes and an MIS approach should be considered in patients with LACC.

Pathological complete response after neoadjuvant chemotherapy with FOLFOX for locally advanced sigmoid colon cancer with diverticulitis: A case report

Introduction and importanceThe standard treatment for locally advanced colon cancer (LACC) without distant metastasis is curative surgery followed by adjuvant chemotherapy, but the long-term outcomes of this strategy are not satisfactory. Neoadjuvant chemotherapy (NAC) is a promising novel option to overcome this issue. Tumor regression is an expected effect of NAC for LACC, but pathological complete response (pCR) is rare. In this report, we present a rare case of pCR after NAC with FOLFOX for LACC in the sigmoid colon.Presentation of caseA 66-year-old woman presented to our hospital with fever and abdominal pain. The diagnosis was LACC in the sigmoid colon with possible invasion of the uterus and pelvic wall, stage IIIC (T4bN1bM0). Furthermore, the tumor was complicated by diverticulitis. A colostomy was performed, followed by NAC with FOLFOX. Six cycles were completed without significant adverse events, and the lesion shrunk remarkably. We performed a curative sigmoidectomy without any postoperative complications. Pathological examination revealed no viable cancer cells, indicating pCR.DiscussionTo the best of our knowledge, this is the first report of pCR after NAC for LACC complicated by diverticulitis. Colostomy before NAC, regimen, and cycle of NAC may be the key to this favorable course.ConclusionWe present a rare case of pathological complete after neoadjuvant chemotherapy with FOLFOX for locally advanced colon cancer in the sigmoid colon complicated by diverticulitis. Our experience may be valuable in determining the optimal treatment strategy for LACC complicated by diverticulitis.

Tumor Regression Grade as a Prognostic Factor in Metastatic Colon Cancer Following Preoperative Chemotherapy

BackgroundThe prognostic value of tumor regression grade (TRG) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy has been explored extensively. However, whether TRG is predictive of outcome in colon cancer following preoperative chemotherapy has not been reported. Materials and MethodsA total of 276 colon cancer patients who had undergone preoperative chemotherapy and surgery in Fudan University Shanghai Cancer Center during the period March 2014 through November 2019 were recruited in this study. 113 (40.9%) and 163 (59.1%) patients were diagnosed with locally advanced colon cancer (LACC) and metastatic colon cancer (mCC) before preoperative chemotherapy, respectively. The TRG was divided into TRG0 (complete response), TRG1 (good response), TRG2 (moderate response), and TRG3 (poor response). ResultsOf the 276 patients 4.0% were TRG0, 5.4% were TRG1, 29.3% were TRG2, 61.2% were TRG3. TRG0 and TRG1 or TRG0, TRG1 and TRG2 were combined to simplify analysis due to limited sample size. In entire cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 80.0%, 68.8% and 43.3% (P = .003). In LACC cohort, TRG was not associated with patients’ prognosis, which largely resulted from limited outcome events. In mCC cohort, the 3-year overall survival for TRG0-1, TRG2, and TRG3 groups were 74.3%, 62.8% to 28.1% (P<0.001). Multivariate analysis demonstrated that TRG was an independent prognostic factor for overall survival in both entire cohort and mCC cohort (TRG3 vs. TRG0-2). ConclusionTRG is a prognostic factor in predicting long-term outcomes of mCC patients treated with preoperative chemotherapy.

Laparoscopic versus open resection in patients with locally advanced colon cancer

BackgroundSurgical resection of locally advanced colon cancer (LACC) is challenging due to tumor size and the frequent need for multivisceral resection. The role of laparoscopic resection in LACC is controversial. This study aims to compare outcomes for laparoscopic versus open surgery in LACC. MethodsA population-based retrospective review was conducted of patients treated at a Provincial Cancer Center for LACC from 2005 to 2015. Patients with non-metastatic T4 colon cancers were included. Descriptive, survival, and recurrence analyses were used. ResultsIn all, 1,328 patients were reviewed, 23% of whom had laparoscopic surgery. A greater number of T4b tumors were removed via an open approach (35.9% vs 12.7%, P < .001). Positive resection margins occurred in 7.5% of laparoscopic and 16.5% of open cases (P < .001), and multivisceral resection was required in 11.0% and 27.7% (P < .001), respectively. Median follow-up was 37 months (interquartile range [IQR] 17–64) during which 48.6% patients died and 42.1% developed recurrence: locoregional (15.0%), distant (35.3%), peritoneal (11.4%). Age, right-sided tumors, nodal status, and laparoscopic approach were independent predictors of peritoneal recurrence. Overall survival (OS) (73 vs 61 months, P = .188) and recurrence-free survival (RFS) (39 vs 31 months, P = .288) were similar with both approaches. Age, nodal, and margin status were predictive of OS and RFS. ConclusionOpen surgical approach is used more frequently when tumors invade adjacent organs or require multivisceral resections. When employed, laparoscopic approach had similar rates of survival and recurrence compared with open approach, but was an independent predictor of peritoneal recurrence. Careful patient selection in operative approach is suggested.

Should be a locally advanced colon cancer still considered a contraindication to laparoscopic resection?

The role of elective laparoscopic resection (LR) for the treatment of locally advanced colon cancer (LACC) is unclear. Most studies have retrospectively investigated the outcomes of LR for pT4 cancers, while clinical T4 (cT4) cancers are excluded in the large randomized controlled trials comparing LR and open resection (OR). The aim of this study was to investigate the outcomes in patients undergoing elective LR for LACC. A prospective single-institution database including consecutive patients undergoing elective LR for clinical LACC (high-risk T3 or T4 N0-2) between March 1996 and March 2017 was retrospectively reviewed. A multivariate analysis was performed to identify predictors of conversion to OR and risk factors for adverse oncologic outcomes. A total of 300 patients undergoing LR for LACC were included. A multi-visceral resection was needed in 17 (5.7%) patients. A total of 63 (21%) LRs were converted to OR, mainly due to suspected adjacent organ invasion (82.5%) or obesity (9.5%). Overall postoperative Clavien-Dindo 3-4 complication rate was 4.7%, with no significant differences between completed and converted LRs. Final pathology showed 18 (6%) pT2, 215 (71.7%) pT3, 54 (18%) pT4a, and 13 (4.3%) pT4b cancers. A R0 resection was achieved in 98.3% of patients. On multivariate analysis, tumor size ≥ 7cm and tumor site (splenic flexure) were the independent risk factors for conversion to OR. A pT4 colon cancer and LNR of 0.25 or greater, but not conversion to OR, were independently associated with both poorer OS and DFS. Clinical LACC should not be considered a contraindication to LR itself. Bulky tumors ≥ 7cm and splenic flexure cancers are at higher risk of conversion to OR; however, there is no increased postoperative morbidity or adverse oncologic outcomes in converted patients.

Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review and meta-analysis.

There is increasing evidence to support the use of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). However, its safety, efficacy and side effect profile is yet to be completely elucidated. This review aims to assess NAC regimens, duration, compare completion rates, intra-operative and post-operative complication profiles and oncological outcomes, in order to provide guidance for clinical practice and further research. PubMed, EMBASE and MEDLINE were searched for a systematic review of the literature from 2000 to 2020. Eight eligible studies were included, with a total of 1213 patients, 752 (62%) of whom received NAC. Of the eight studies analysed, two were randomised controlled trials comparing neoadjuvant chemotherapy followed by oncological resection to upfront surgery and adjuvant chemotherapy, three were prospective single-arm phase II trials analysing neoadjuvant chemotherapy followed by surgery only, one was a retrospective study comparing neoadjuvant chemotherapy followed by surgery versus surgery first followed by adjuvant chemotherapy and the remaining two were single-arm retrospective studies of neoadjuvant chemotherapy followed by surgery. All cases of LACC were determined and staged by computed tomography; majority of the studies defined LACC as T3 with extramural depth of 5 mm or more, T4 and/or nodal positivity. NAC administered was either folinic acid, fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) with the exception of one study which utilised 5-fluorouracil and mitomycin. Most studies had NAC completion rates of above 83% with two notable exceptions being Zhou et al. and The Colorectal Cancer Chemotherapy Study Group of Japan who both recorded a completion rate of 52%. Time to surgery from completion of NAC ranged on average from 16 to 31 days. The anastomotic leak rate in the NAC group ranged from 0 to 4.5%, with no cases of postoperative mortality. The R0 resection rate in the NAC group was 96.1%. Meta-analysis of both RCTs included in this study showed that neoadjuvant chemotherapy increased the likelihood of a negative resection margin T3/4 advanced colon cancer (pooled relative risk of 0.47 with a 95% confidence interval) with no increase in adverse consequence of anastomotic leak, wound infection or return to theatre. Our systematic review and meta-analysis show that NAC is safe with an acceptable side effect profile in the management of LACC. The current data supports an oncological benefit for tumour downstaging and increased in R0 resection rate.

Neoadjuvant chemoradiotherapy for patients with unresectable radically locally advanced colon cancer: a potential improvement to overall survival and decrease to multivisceral resection

BackgroundThe management of unresectable locally advanced colon cancer (LACC) remains controversial, as resection is not feasible. The goal of this study was to evaluate the treatment outcomes and toxicity of neoadjuvant chemoradiotherapy (NACRT) followed with surgery and adjuvant chemotherapy in patients with unresectable radically LACC.MethodsWe included patients who were diagnosed at our institution, 2010–2018. The neoadjuvant regimen consisted of radiotherapy and capecitabine/ 5-fluorouracil-based chemotherapy.ResultsOne hundred patients were identified. The median follow-up time was 32 months. The R0 resection rate, adjusted nonmultivisceral resection rate and bladder preservation rate were 83.0, 43.0 and 83.3%, respectively. The pCR and clinical-downstaging rates were 18, and 81.0%%, respectively. The 3-year PFS and OS rates for all patients were 68.6 and 82.1%, respectively. Seventeen patients developed grade 3–4 myelosuppression, which was the most common adverse event observed after NACRT. Tumor perforation occurred in 3 patients during NACRT. The incidence of grade 3–4 surgery-related complications was 7.0%. Postoperative anastomotic leakage was observed in 3 patients.ConclusionsNACRT followed by surgery was feasible and safe for selected patients with LACC, and can be used as a conversion treatment to achieve satisfactory downstaging, long-term survival and quality of life, with acceptable toxicities.

Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review.

Preoperative or neoadjuvant chemotherapy (NAC) has emerged as a novel alternative to treat locally advanced colon cancer (LACC), as in other gastrointestinal malignancies. However, evidence of its efficacy and safety has not yet been gathered in the literature. The aim of the present study was to perform an extensive review of the scientific evidence for NAC in patients with LACC. PubMed, EMBASE, MEDLINE and Cochrane Library were searched for a systematic review of the literature from 2010 to 2019. Six eligible studies were included, with a total of 27,937 patients, 1232 of them (4.4%) treated with NAC. There were only one randomized controlled trial, three phase II non-randomized single arm studies and two retrospective studies. The baseline computed tomography scan showed that most of patients had a T3 tumor. The completion rate of the planned neoadjuvant treatment ranged from 52.5 to 93.8%. Between 97.2 and 100% of patients had the scheduled surgery. The median tumor volume reduction after NAC ranged from 62.5 to 63.7%. The anastomotic leak rate in the NAC group ranged from 0 to 7%, with no cases of postoperative mortality. There was major pathological tumor regression in 4-34.7% of cases. Between 84 and 100% of NAC patients had R0-surgery. Survival after NAC seems to be encouraging although significant improvement has only been proven in T4b tumours. According to our systematic review, the NAC may be a safe and effective emerging therapeutic alternative for treating LACC. This approach, which is still being tested, increases the reliance on accurate radiological staging.