Localized colorectal cancer database integrating 4 randomized controlled trials; (JCOG2310A).

Although phase III randomized controlled trials (RCTs) represent the most robust statistical approach for answering clinical questions, they require massive expenditures in terms of time, labor, and funding. Ancillary and supplementary analyses using RCTs are sometimes conducted as alternative approaches to answering clinical questions, but the available integrated databases of RCTs are limited. In this background, the Colorectal Cancer Study Group (CCSG) of the Japan Clinical Oncology Group (JCOG) established a database of ancillary studies integrating four phase III RCTs (JCOG0212, JCOG0404, JCOG0910 and JCOG1006) conducted by the CCSG to investigate specific clinicopathological factors in pStage II/III colorectal cancer (JCOG2310A). This database will be updated by adding another clinical trial data and accelerating several analyses that are clinically relevant in the management of localized colorectal cancer. This study describes the details of this database and planned and ongoing analyses as an initiative of JCOG cOlorectal Young investigators (JOY).

Impact of resection for ovarian metastases from colorectal cancer and clinicopathologic analysis: A multicenter retrospective study in Japan.

Aim: The aim of this study was to clarify the significance of resection of ovarian metastases from colorectal cancer and to identify the clinicopathologic characteristics. Methods: In this multicenter retrospective study, we evaluated data on ovarian metastases from colorectal cancer obtained from patients at 20 centers in Japan between 2000 and 2014. We examined the impact of resection on the prognosis of patients with ovarian metastases and examined prognostic factors. Results: The study included 296 patients with ovarian metastasis. The 3-y overall survival rate was 68.6% for solitary ovarian metastases. In all cases of this cohort, the 3-y overall survival rates after curative resection, noncurative resection, and nonresection were 65.9%, 31.8%, and 6.1%, respectively (curative resection vs noncurative resection [P < 0.01] and noncurative resection vs nonresection [P < 0.01]). In the multivariate analysis of prognostic factors, tumor size of ovarian metastasis (P < 0.01), bilateral ovarian metastasis (P = 0.01), peritoneal metastasis (P < 0.01), pulmonary metastasis (P = 0.04), liver metastasis (P < 0.01), and remnant of ovarian metastasis (P < 0.01) were statistically significantly different. Conclusion: The prognosis after curative resection for solitary ovarian metastases was shown to be relatively favorable as Stage IV colorectal cancer. Resection of ovarian metastases, not only curative resection but also noncurative resection, confers a survival benefit. Prognostic factors were large ovarian metastases, bilateral ovarian metastases, the presence of extraovarian metastases, and remnant ovarian metastases.

Prognostic impact of primary tumour location after curative resection in Stage I-III colorectal cancer: a single-centre retrospective study.

OBJECTIVE: The relationship of tumour site with post-recurrence course and outcome after primary surgery in resectable colorectal cancer is unclear. This study investigated the prognostic impact of primary tumour location following radical resection without preoperative treatment in Stage I-III colorectal cancer. METHODS: We analyzed 3770 patients with Stage I-III colorectal cancer who underwent curative resection at our hospital during 2000-15. We defined the right-sided colon as the cecum, ascending colon and transverse colon, and the left-sided colon as the descending colon, sigmoid and rectosigmoid junction. Patients were divided into three groups according to tumour site: right-sided colon, left-sided colon and rectum. Endpoints were overall survival, recurrence-free survival by stage and survival after recurrence, respectively. RESULTS: The 5-year overall survival rates of patients with stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 98.2, 97.3 and 97.2%, respectively (P = 0.488). The 5-year overall survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 96.2, 88.7 and 83.0, respectively (P = 0.070). The 5-year overall survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 88.7, 83.0 and 80.2, respectively (P = 0.001). The 5-year recurrence-free survival rates of patients with Stage I left-sided colon cancer, right-sided colon cancer and rectal cancer were 95.1, 94.5 and 90.6% (P = 0.027). The 5-year recurrence-free survival rates of patients with Stage II left-sided colon cancer, right-sided colon cancer and rectal cancer were 85.2, 90.2 and 76.1%, respectively (P < 0.001). The 5-year recurrence-free survival rates of patients with Stage III left-sided colon cancer, right-sided colon cancer and rectal cancer were 75.3, 75.3 and 59.8%, respectively (P < 0.001). Right-sided colon cancer was significantly associated with better recurrence-free survival compared with left-sided colon cancer (HR 1.29, 95% CI 1.03-1.63; P = 0.025) and rectal cancer (HR 1.89, 95% CI 1.51-2.38; P < 0.001) after adjusting for clinical factors. Amongst patients with recurrence, right-sided colon cancer was significantly associated with poorer survival after recurrence compared with left-sided colon cancer (HR 0.68, 95% CI 0.48-0.97; P = 0.036), and showed a tendency towards poorer survival after recurrence compared with rectal cancer (HR 0.79, 95% CI 0.57-1.10; P = 0.164). CONCLUSIONS: In Stage I-III colorectal cancer without preoperative treatment, our results suggest that the three tumour sites (right-sided colon, left-sided colon or rectum) may have prognostic significance for recurrence-free survival and survival after recurrence, rather than sidedness alone.

Proportions and characteristics of interval cancer in annual fecal immunochemical test screening and postcolonoscopy colorectal cancer: Results from a Japanese multicenter prospective study using questionnaires, the C-DETECT study.

OBJECTIVES: There are several types of colorectal cancer (CRC) according to the detection methods and intervals, including interval CRC (iCRC) and postcolonoscopy CRC (PCCRC). We aimed to examine their proportions and characteristics. METHODS: We conducted a multicenter prospective study using questionnaires in Japan ("C-DETECT study"), in which differences in CRC characteristics according to detection methods and intervals were examined from consecutive adult patients. Because the annual fecal immunochemical test (FIT) was used in population-based screening, the annual FIT-iCRC was assessed. RESULTS: In total, 1241 CRC patients (1064 with invasive CRC) were included. Annual FIT-iCRC (a), 3-year PCCRC (b), and CRC detected within 1 year after a positive FIT with noncompliance to colonoscopy (c) accounted for 4.5%, 7.0%, and 3.9% of all CRCs, respectively, and for 3.9%, 5.4%, and 4.3% of invasive CRCs, respectively. The comparison among these (a, b, c) and other CRCs (d) demonstrated differences in the proportions of ≥T2 invasion ([a] 58.9%, [b] 44.8%, [c] 87.5%, [d] 73.0%), metastasis ([a] 33.9%, [b] 21.8%, [c] 54.2%, [d] 43.9%), right-sided CRC ([a] 42.9%, [b] 40.2%, [c] 18.8%, [d] 28.6%), and female sex ([a] 53.6%, [b] 49.4%, [c] 27.1%, [d] 41.6%). In metastatic CRC, (a) and (b) showed a higher proportions of BRAF mutations ([a] [b] 12.0%, [c] [d] 3.1%). CONCLUSIONS: Annual FIT-iCRC and 3-year PCCRC existed in nonnegligible proportions. They were characterized by higher proportions of right-sided tumors, female sex, and BRAF mutations. These findings suggest that annual FIT-iCRC and 3-year PCCRC may have biological features different from those of other CRCs.

Cost-effectiveness of surveillance intervals after curative resection of colorectal cancer.

BACKGROUND: Major guidelines consistently recommend 5 years of postoperative surveillance for patients with colorectal cancer. However, they differ in their recommendations for examination intervals and whether they should vary according to disease stage. Furthermore, there are no reports on the cost-effectiveness of the different surveillance schedules. The objective of this study is to identify the most cost-effective surveillance intervals after curative resection of colorectal cancer. METHODS: A total of 3701 patients who underwent curative surgery for colorectal cancer at the National Cancer Center Hospital were included. A cost-effectiveness analysis was conducted for the five surveillance strategies with reference to the guidelines. Expected medical costs and quality-adjusted life years after colorectal cancer resection were calculated using a state-transition model by Monte Carlo simulation. The incremental cost-effectiveness ratio per quality-adjusted life years gained was calculated for each strategy, with a maximum acceptable value of 43 500-52 200 USD (5-6 million JPY). RESULTS: Stages I, II and III included 1316, 1082 and 1303 patients, respectively, with 45, 140 and 338 relapsed cases. For patients with stage I disease, strategy 4 (incremental cost-effectiveness ratio $26 555/quality-adjusted life year) was considered to be the most cost-effective, while strategies 3 ($83 071/quality-adjusted life year) and 2 ($289 642/quality-adjusted life year) exceeded the threshold value. In stages II and III, the incremental cost-effectiveness ratio for strategy 3 was the most cost-effective option, with an incremental cost-effectiveness ratio of $18 358-22 230/quality-adjusted life year. CONCLUSIONS: In stage I, the cost-effectiveness of intensive surveillance is very poor and strategy 4 is the most cost-effective. Strategy 3 is the most cost-effective in stages II and III.

Prognostic impact of extramural venous invasion detected by contrast-enhanced CT colonography in colon cancer.

BACKGROUND: The impact of computed tomography (CT)-detected extramural venous invasion on the recurrence of colon cancer is not fully understood. The aim of this study was to investigate the clinical significance of extramural venous invasion diagnosed before surgery by contrast-enhanced CT colonography using three-dimensional multiplanar reconstruction images. METHODS: Patients with colon cancer staged greater than or equal to T2 and/or stage I-III who underwent contrast-enhanced CT colonography between 2013 and 2018 at the National Cancer Center Hospital in Japan were retrospectively investigated for CT-detected extramural venous invasion. Inter-observer agreement for the detection of CT-detected extramural venous invasion was evaluated and Kaplan-Meier survival curves were plotted for recurrence-free survival using CT-TNM staging and CT-detected extramural venous invasion. Preoperative clinical variables were analysed using Cox regression for recurrence-free survival. RESULTS: Out of 922 eligible patients, 544 cases were analysed (50 (9.2 per cent) were diagnosed as positive for CT-detected extramural venous invasion and 494 (90.8 per cent) were diagnosed as negative for CT-detected extramural venous invasion). The inter-observer agreement for CT-detected extramural venous invasion had a κ coefficient of 0.830. The group positive for CT-detected extramural venous invasion had a median follow-up of 62.1 months, whereas the group negative for CT-detected extramural venous invasion had a median follow-up of 60.7 months. When CT-TNM stage was stratified according to CT-detected extramural venous invasion status, CT-T3 N(-)extramural venous invasion(+) had a poor prognosis compared with CT-T3 N(-)extramural venous invasion(-) and CT-stage I (5-year recurrence-free survival of 50.6 versus 89.3 and 90.1 per cent respectively; P < 0.001). In CT-stage III, the group positive for CT-detected extramural venous invasion also had a poor prognosis compared with the group negative for CT-detected extramural venous invasion (5-year recurrence-free survival of 52.0 versus 78.5 per cent respectively; P = 0.003). Multivariable analysis revealed that recurrence was associated with CT-T4 (HR 3.10, 95 per cent c.i. 1.85 to 5.20; P < 0.001) and CT-detected extramural venous invasion (HR 3.08, 95 per cent c.i. 1.90 to 5.00; P < 0.001). CONCLUSION: CT-detected extramural venous invasion was found to be an independent predictor of recurrence and could be used in combination with preoperative TNM staging to identify patients at high risk of recurrence.

How Does Omitting Additional Surgery After Local Excision Affect the Prognostic Outcome of Patients With High-risk T1 Colorectal Cancer?

OBJECTIVE: To investigate how omitting additional surgery after local excision (LE) affects patient outcomes in high-risk T1 colorectal cancer (CRC). BACKGROUND: It is debatable whether additional surgery should be performed for all patients with high-risk T1 CRC regardless of the tolerability of invasive procedures. METHODS: Patients who had received LE for T1 CRC at the Japanese Society for Cancer of the Colon and Rectum institutions between 2009 and 2016 were analyzed. Those who had received additional surgical resection and those who did not were matched one-on-one by the propensity score-matching method. A total of 401 propensity score-matched pairs were extracted from 1975 patients at 27 Japanese Society for Cancer of the Colon and Rectum institutions and were compared. RESULTS: Regional lymph node metastasis was observed in 31 (7.7%) patients in the LE + surgery group. Comparatively, the incidence of oncologic adverse events was low in the LE-alone group, such as the 5-year cumulative risk of local recurrence (4.1%) or overall recurrence (5.5%). In addition, the difference in the 5-year cancer-specific survival between the LE + surgery and LE-alone groups was only 1.8% (99.7% and 97.9%, respectively), whereas the 5-year overall survival was significantly lower in the LE-alone group than in the LE + surgery group [88.5% vs 94.5%, respectively ( P = 0.002)]. CONCLUSIONS: Those who had decided to omit additional surgery at the dedicated center for CRC treatment presented a small number of oncologic events and a satisfactory cancer-specific survival, which may suggest an important role of risk assessment regarding nononcologic adverse events to achieve a best practice for each individual with high-risk T1 tumors.

Prognostic Relevance of Primary Tumor Sidedness in Early-stage Colorectal Cancer: An Integrated Analysis of 4 Randomized Controlled Trials (JCOG2003A).

OBJECTIVE: The aim of this study was to determine the genuine prognostic relevance of primary tumor sidedness (PTS) in patients with early-stage colorectal cancer (CRC). BACKGROUND: The prognostic relevance of PTS in early-stage CRC remains a topic of debate. Several large epidemiological studies investigated survival only and did not consider the risk of recurrence so far. METHODS: Patients with stage II/III adenocarcinoma of the colon and upper rectum from 4 randomized controlled trials were analyzed. Survival outcomes were compared according to the tumor location: right-sided (cecum to transverse colon) or left-sided (descending colon to upper rectum). RESULTS: A total of 4113 patients were divided into a right-sided group (N=1349) and a left-sided group (N=2764). Relapse-free survival after primary surgery was not associated with PTS in all patients and each stage [hazard ratio (HR) adjusted =1.024 (95% CI: 0.886-1.183) in all patients; 1.327 (0.852-2.067) in stage II; and 0.990 (0.850-1.154) in stage III]. Also, overall survival after primary surgery was not associated with PTS in all patients and each stage [HR adjusted =0.879 (95% CI: 0.726-1.064) in all patients; 1.517 (0.738-3.115) in stage II; and 0.840 (0.689-1.024) in stage III]. In total, 795 patients (right-sided, N=257; left-sided, N=538) developed recurrence after primary surgery. PTS was significantly associated with overall survival after recurrence (HR adjusted =0.773, 95% CI: 0.627-0.954). CONCLUSIONS: PTS had no impact on the risk of recurrence for stage II/III CRC. Treatment stratification based on PTS is unnecessary for early-stage CRC.

Total neoadjuvant therapy followed by a watch-and-wait strategy for patients with rectal cancer (TOWARd): protocol for single-arm phase II/III confirmatory trial (JCOG2010).

BACKGROUND: Radical surgery is the standard treatment for rectal cancer, but can impact quality of life. Recently, the concept of total neoadjuvant therapy with a watch-and-wait strategy has been proposed in which patients with a cCR after total neoadjuvant therapy do not proceed to surgery. However, most investigations of a watch-and-wait strategy have reported cases where cCR was achieved coincidentally via total neoadjuvant therapy. The aim is to assess whether total neoadjuvant therapy is effective in early-stage rectal cancer in patients that achieve cCR and are offered a watch-and-wait strategy. METHODS: JCOG2010 (TOWARd) is a multi-institutional, single-arm phase II/III confirmatory investigation of the safety and efficacy of total neoadjuvant therapy followed by a watch-and-wait strategy for rectal cancer. Key eligibility criteria include cT2-3 N0 M0 rectal adenocarcinoma, tumour diameter less than or equal to 5 cm, age 18-75 years, performance status 0-1, and no history of pelvic irradiation or rectal surgery. Total neoadjuvant therapy involves neoadjuvant chemoradiotherapy (capecitabine and radiotherapy: 45 Gy/25 fractions to the whole pelvis plus boost of 5.4 Gy/3 fractions to the primary tumour) followed by consolidation chemotherapy (four cycles of capecitabine/oxaliplatin). Patients will be re-staged every 8 weeks after total neoadjuvant therapy, and those who achieve cCR will undergo a watch-and-wait strategy, those with near complete response will undergo a watch-and-wait strategy or local resection, and those with an incomplete response will undergo radical surgery. The primary endpoint is the cCR rate in phase II and 5-year overall survival in phase III. Secondary endpoints include postoperative anal, urinary, and sexual function. A total of 105 patients (phase II, 40 patients; phase III, 65 patients) will be enrolled over 3.5 years. CONCLUSION: This trial will determine whether total neoadjuvant therapy and a watch-and-wait strategy is an effective alternative to radical surgery for early-stage rectal cancer in patients with cT2-3 N0 M0 and tumour size less than or equal to 5 cm. REGISTRATION NUMBER: jRCTs031220288 (https://jrct.niph.go.jp/en-latest-detail/jRCTs031220288).

A multicenter prospective observational study of lymph node metastasis patterns and short-term outcomes of extended lymphadenectomy in right-sided colon cancer.

Background: The lymph node metastasis rate in right-sided colon cancer is unknown, and the optimal central vascular ligation level remains controversial. We aimed to determine the lymph node metastasis rate and short-term results of radical surgery with extended lymph node dissection in right-sided colon cancer. Methods: This prospective multicenter observational study included patients with stage II/III right-sided colon cancer from five cancer hospitals. The metastasis rate of each node station was analyzed according to tumor location and main feeding artery. Results: Between April 2018 and August 2021, 208 patients underwent dissection around the superior mesenteric artery (SMA) and vein (SMV). In transverse colon cancer, 7.5% and 2.5% of metastases occurred around the SMV and SMA at the root of the middle colic artery (MCA), respectively; 6.7% and 6.7% at the root of the right colic artery. In caecal cancer, 1.9% of metastases occurred around the SMV and 1.9% around the SMA. In ascending colon cancer, the rate was 1.1% around the SMV. Of the tumors, 17% fed mainly by the ileocolic artery had node metastases along the middle or right colic artery, as did 66.7% fed mainly by the right colic artery and 41.2% fed by the MCA (p = 0.01). Postoperative complications occurred in 42 patients (20.2%). Conclusion: Routine prophylactic extended lymphadenectomy around the SMA might not be necessary in caecum and ascending colon cancer. Dissection around the SMA may be necessary in cases of transverse colon cancer or when the feeding artery is the MCA.

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 chemotherapy is poor. Preoperative chemotherapy for LACC patients with risk factors such as cT4bN+ or cT3-4aN2-3 has attracted attention. Here, the authors describe the rationale and design of JCOG2006, a randomized phase II study comparing preoperative chemotherapy with mFOLFOX6 versus FOLFOXIRI for LACC. Their efficacy and safety are evaluated and a determination of which is the more promising treatment will be conducted in a subsequent phase III trial. A total of 86 patients will be accrued from 44 institutions over 2 years. The primary end point is the proportion of patients with a Tumor Regression Score of 0-2, and secondary end points include overall survival, response rate and adverse events. Clinical Trial Registration: jRCTs031210365 (https://jrct.niph.go.jp/).

International standardization and optimization group for intersphincteric resection (ISOG-ISR): modified Delphi consensus on anatomy, definition, indication, surgical technique, specimen description and functional outcome.

AIM: Intersphincteric resection (ISR) is an oncologically complex operation for very low-lying rectal cancers. Yet, definition, anatomical description, operative indications and operative approaches to ISR are not standardized. The aim of this study was to standardize the definition of ISR by reaching international consensus from the experts in the field. This standardization will allow meaningful comparison in the literature in the future. METHOD: A modified Delphi approach with three rounds of questionnaire was adopted. A total of 29 international experts from 11 countries were recruited for this study. Six domains with a total of 37 statements were examined, including anatomical definition; definition of intersphincteric dissection, intersphincteric resection (ISR) and ultra-low anterior resection (uLAR); indication for ISR; surgical technique of ISR; specimen description of ISR; and functional outcome assessment protocol. RESULTS: Three rounds of questionnaire were performed (response rate 100%, 89.6%, 89.6%). Agreement (≥80%) reached standardization on 36 statements. CONCLUSION: This study provides an international expert consensus-based definition and standardization of ISR. This is the first study standardizing terminology and definition of deep pelvis/anal canal anatomy from a surgical point of view. Intersphincteric dissection, ISR and uLAR were specifically defined for precise surgical description. Indication for ISR was determined by the rectal tumour's maximal radial infiltration (T stage) below the levator ani. A new surgical definition of T3isp was reached by consensus to define T3 low rectal tumours infiltrating the intersphincteric plane. A practical flowchart for surgical indication for uLAR/ISR/abdominoperineal resection was developed. A standardized ISR surgical technique and functional outcome assessment protocol was defined.

Utility of circulating tumour DNA for prognosis and prediction of therapeutic effect in locally recurrent rectal cancer: study protocol for a multi-institutional, prospective observational study (JCOG1801A1, CAP-LR study).

INTRODUCTION: In locally recurrent rectal cancer (LRRC), surgery is a standard treatment for resectable disease. However, short-term and long-term outcomes are unsatisfactory due to the invasive nature of surgical procedures and the high proportion of local recurrence. Consequently, the identification of reliable prognostic and predictive biomarkers to guide treatment decisions may improve outcomes. The presence of circulating tumour DNA (ctDNA) in plasma after surgery may signify the presence of minimal residual disease (MRD) in various cancers. Therefore, we have launched a multi-institutional prospective observational study of ctDNA for MRD detection in conjunction with JCOG1801, a randomised, controlled phase III trial evaluating the efficacy of preoperative chemoradiotherapy (pre-CRT) compared with up-front surgery for LRRC (jRCTs031190076, NCT04288999). METHODS AND ANALYSIS: JCOG1801A1 is the first correlative study that assesses ctDNA in LRRC patients enrolled in JCOG1801. Patients randomised to up-front surgery will provide whole blood samples at three time points (prior to surgery, after surgery and after postoperative chemotherapy); those to pre-CRT will provide at five time points (prior to pre-CRT, after pre-CRT, prior to surgery, after surgery and after postoperative chemotherapy). Cell-free DNA will be extracted from plasma and analysed by Guardant Reveal, a tumour tissue-agnostic assay that assesses both genomic alterations and methylation patterns to determine the presence or absence of ctDNA. We will compare the prognosis and treatment response of patients according to their ctDNA status after surgery and at other time points. ETHICS AND DISSEMINATION: The study protocol received approval from the Institutional Review Board of National Cancer Center Hospital East on behalf of the participating institutions in February 2023. The study is conducted in accordance with the precepts established in the Declaration of Helsinki and Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Written informed consent will be obtained from all eligible patients prior to registration.

Phase II biomarker identification study of anti-VEGF agents with FOLFIRI for pretreated metastatic colorectal cancer.

Chemotherapy plus antiangiogenic agents, including bevacizumab, ramucirumab and aflibercept, is a standard second-line treatment for patients with metastatic colorectal cancer, but which specific agents should be selected is ambiguous due to a lack of clear evidence from prospective studies. Previous reports have suggested ramucirumab and aflibercept could be more effective than bevacizumab in patients with high VEGF-D and high VEGF-A, respectively. JCOG2004 is a three-arm, randomized, phase II study to identify predictive biomarkers for these agents in patients who have failed first-line treatment. The study will enroll 345 patients from 52 institutions for 2 years, with progression-free survival in high VEGF-D (bevacizumab vs ramucirumab) and high VEGF-A (bevacizumab vs aflibercept) serving as the primary end point. Clinical Trial Registration: jRCTs031220058 (www.jrct.niph.go.jp).

Lateral pelvic lymph node metastasis in T2 low rectal cancer: is TME alone sufficient for cure?

BACKGROUND: Some patients with even T2 low rectal cancer are known to develop lateral pelvic lymph node metastasis. This study aimed to investigate real-world evidence regarding lateral nodal metastasis on T2 low rectal cancer treatment. METHODS: Consecutive patients with pathological T2 low rectal adenocarcinoma who underwent curative-intent surgery between January 2007 and December 2015 at two Japanese cancer centres dedicated to lateral pelvic lymph node dissection were identified and included in the analysis. Lateral pelvic lymph node metastasis was defined as pathologically confirmed metastatic lateral pelvic lymph node or lateral-local recurrence after primary surgery. RESULTS: A total of 215 consecutive patients, including 101 and 114 patients who did and did not undergo bilateral lateral pelvic lymph node dissection, were included in the analysis. Overall, 19 (8.8%) patients had lateral pelvic lymph node metastasis, including 13 with pathologically confirmed metastatic lateral pelvic lymph node and six with lateral-local recurrence. A total of 10 (4.7%) patients had local recurrence, including six with lateral-local recurrence, two with central-local recurrence and two with anastomotic recurrence. Five/7-year cumulative risks of lateral-local recurrence in patients with and without lateral pelvic lymph node dissection were 1.1/1.1% and 3.9/5.2%, respectively. CONCLUSION: The problem of the relatively high rate of lateral local recurrence remains in treating T2 low rectal cancer with only total mesorectal excision. The selection of high-risk patients of lateral pelvic lymph node metastasis and the indication of additional treatment in T2 low rectal cancer should be discussed further.

A review of 14 cases of perianal Paget's disease: characteristics of anorectal cancer with pagetoid spread.

BACKGROUND: Perianal Paget's disease (PPD) is an intraepithelial invasion of the perianal skin and is frequently associated with underlying anorectal carcinoma. The relatively rare nature of this disease has made it difficult to develop treatment recommendations. This study aims to analyze the clinical and pathological features of perianal Paget's disease (PPD) and to explore rational treatment options and follow-up for this disease. METHODS: The National Cancer Center Hospital database was searched for all cases of perianal Paget's disease diagnosed between 2006 and 2021. In the 14 patients identified, we reviewed the diagnosis, management, and outcomes of adenocarcinoma with pagetoid spread, including suspected or recurrent cases. RESULTS: All 14 cases met the inclusion criteria. The median follow-up period after diagnosis was 4.5 (range, 0.1-13.0) years. Pagetoid spread before initial treatment was suspected in 12 cases (85.7%). Underlying rectal cancer was identified in 6 cases, and no primary tumor was detected in the other 6 cases. Seven patients had recurrent disease, with the median time to recurrence of 34.6 (range, 19.2-81.7) months. The time to the first relapse was 3 months, and that to the second relapse was 6 months. The overall 5-year survival rate was 90.0%. CONCLUSIONS: Endoscopic and radiologic evaluation, as well as immunohistologic examination, should be performed. is to differentiate PPD with and without underlying anorectal carcinoma. The time to first recurrence varies widely, and long-term and regular follow-up for more than 5 years is considered necessary for local recurrence and distant metastasis.

Prognostic differences between oligometastatic and polymetastatic disease after resection in patients with colorectal cancer and hepatic or lung metastases: Retrospective analysis of a large cohort at a single institution.

BACKGROUND: Long-term survival data are lacking, and prognostic factors are not well-defined for patients with colorectal cancer and hepatic or lung metastases. This study evaluated the outcomes after resection of oligometastatic hepatic or lung metastases from colorectal cancer and sought to identify prognostic factors. METHODS: We retrospectively investigated 1,123 patients with colorectal cancer and hepatic or pulmonary metastases who underwent curative surgery between January 1991 and December 2016. RESULTS: Of the 1,123 patients, 719 had hepatic metastases, 287 had pulmonary metastases, and 117 had both. The 5-year overall survival rate was 52.3% in the hepatic metastases group, 70.4% in the pulmonary metastases group, and 71.4% in the hepatic and pulmonary metastases group (P < .001). In total, 1,045 patients had oligometastases (1-5 metastatic lesions in 1 or 2 organs) and 78 had polymetastases (≥6 metastases in 1 or 2 organs). Prognosis was significantly better in patients with oligometastases than in those with polymetastases. The 5-year overall survival rate was 59.0% in the oligometastases group and 35.3% in the polymetastases group (P < .001); the respective 5-year relapse-free survival rates were 37.5% and 11.6% (P < .001). Multivariable analysis identified predictors of both poor overall survival and relapse-free survival to be a high carcinoembryonic antigen level before the first metastasectomy, largest metastasis measuring ≥2 cm, polymetastases, and synchronous metastases. CONCLUSION: Prognosis after curative resection was better in patients with oligometastatic colorectal cancer in the liver or lung than in those with polymetastases. Multidisciplinary decision-making strategies, including about surgery, should be based on number of metastases rather than their site.

Risk of non-colorectal cancer-related death in elderly patients with the disease: A comparison of five preoperative risk assessment indices.

BACKGROUND: A considerable number of elderly patients with colorectal cancer (CRC) die of non-CRC-related causes. The Controlling Nutritional Status (CONUT) score, American Society of Anesthesiologists Physical Status classification, Charlson Comorbidity Index, National Institute on Aging, and National Cancer Institute Comorbidity Index, and Adult Comorbidity Evaluation-27 score are all known predictors of survival in patients with CRC. However, the utility of these indices for predicting non-CRC-related death in elderly CRC patients is not known. METHODS: The study population comprised 364 patients aged 80 years or more who received curative resection for stage I-III CRC between 2000 and 2016. The association of each index with non-CRC-related death was compared by competing-risks analysis such as the cumulative incidence function and proportional subdistribution hazards regression analysis as well as time-dependent receiver-operating characteristic (ROC) analysis. RESULTS: There were 85 deaths (40 CRC-related and 45 non-CRC-related) during a median observation period of 53.2 months. Cumulative incidence function analysis identified CONUT score as the most suitable for risk stratification for non-CRC-related death. In proportional subdistribution hazards regression, risk of non-CRC-related death increased significantly as CONUT score worsened (2/3/4 vs. 0/1, hazard ratio 1.73, 95% confidence interval [CI] 0.91-3.15; ≥5 vs. 2/3/4, hazard ratio 2.71, 95% CI 1.08-6.81). Time-dependent ROC curve analysis showed that CONUT score were consistently superior to other indices during the 5-year observation period. CONCLUSIONS: The majority of deaths in elderly patients with CRC were not CRC-related. CONUT score was the most useful predictor of non-CRC-related death in these patients.

Treatment outcomes and prognostic factors in 47 patients with primary anorectal malignant melanoma in the immune therapy era.

PURPOSE: Primary anorectal melanoma (ARM) accounts for approximately 1.2% of all melanomas and 16.5% of all mucosal melanomas. ARM is associated with the shortest interval to disease progression and the highest rate of metastasis; however, optimal therapeutic strategies for ARM remain controversial. This study aimed to assess the ideal surgical intervention for ARM and to determine the effect of immune checkpoint inhibitors (ICI). METHODS: We included 47 patients with ARM treated at the National Cancer Center Hospital in Japan from 2011 to 2020. We performed a survival analysis for each of these groups: (i) patients with ARM (n = 47); (ii) operable non-stage IV cases at initial presentation (n = 35); and (iii) stage IV cases (n = 32). RESULTS: The 5-year overall survival (OS) was 53.6%, and the median OS was 78.7 months in patients with ARM. No statistically significant difference in 5-year OS was found between rectal and anal sites (50.9% vs. 56.7%). In the non-stage IV subgroup, the type of surgery (abdominoperineal resection or wide local excision) did not correlate with OS (HR 1.85; 95% CI 0.46-7.5; p = 0.39). In the stage IV subgroup, the 2-year OS of the ICI treatment group was 61.4%, whereas that of the dacarbazine regimen group was 0% (p = 0.048). CONCLUSION: Our ARM prognosis was better than that of previous studies. Our findings suggest that the availability of ICI therapy may improve survival in patients with advanced ARM. However, further research is warranted to identify both the clinical and molecular predictors of response to improve patient selection.

Prognostic Role for Primary Tumor Location in Patients With Colorectal Liver Metastases: A Comparison of Right-Sided Colon, Left-Sided Colon, and Rectum.

BACKGROUND: Although right-sided colon cancer is increasingly recognized as having a worse prognosis than left-sided colorectal cancer for colorectal liver metastases, little is known about the differences between the left-sided colon and rectum. OBJECTIVE: This study evaluated the prognostic value of primary tumor location in patients with colorectal liver metastases by examining the left-sided colon and rectum separately. DESIGN: This was a retrospective study from 2003 to 2017. SETTINGS: The study was conducted in a National Cancer Center Hospital. PATIENTS: The study cohort included 489 patients with colorectal liver metastases from right-sided colon cancer ( n = 119, 24%), left-sided colon cancer ( n = 251, 51%), or rectal cancer ( n = 119, 24%) who underwent hepatic resection. MAIN OUTCOME MEASURES: Primary outcomes were relapse-free survival and overall survival. RESULTS: Five-year relapse-free survival rates for patients with right-sided colon cancer, left-sided colon cancer, and rectal cancer were 28.6%, 34.1%, and 26.4%, and 5-year overall survival rates were 53.9%, 70.3%, and 60.8%. Multivariable analysis revealed significant differences in relapse-free survival and overall survival between left-sided colon cancer and rectal cancer (relapse-free survival: HR = 1.37, p = 0.03; overall survival: HR = 1.49, p = 0.03) and between left-sided colon cancer and right-sided colon cancer (relapse-free survival: HR = 1.39, p = 0.02; overall survival: HR = 1.60, p = 0.01), but not between right-sided colon cancer and rectal cancer. In patients with recurrence ( n = 325), left-sided colon cancer had the lowest multiple-site recurrence rate and the highest surgical resection rate for recurrence (left-sided colon cancer, 20%/46%; right-sided colon cancer, 32%/30%; rectal cancer, 26%/39%). LIMITATIONS: This study was retrospective in design. CONCLUSIONS: Rectal cancer was associated with worse relapse-free survival and overall survival compared with left-sided colon cancer in patients with colorectal liver metastases who underwent hepatic resection. Our findings suggest that the left-sided colon and rectum should be considered distinct entities in colorectal liver metastases. See Video Abstract at http://links.lww.com/DCR/B882 . PAPEL PRONSTICO DE LA UBICACIN DEL TUMOR PRIMARIO EN PACIENTES CON METSTASIS HEPTICAS COLORRECTALES UNA COMPARACIN ENTRE COLON DERECHO, COLON IZQUIERDO Y RECTO: ANTECEDENTES:Aunque se reconoce cada vez más que el cáncer de colon del lado derecho tiene un peor pronóstico que el cáncer colorrectal del lado izquierdo para las metástasis hepáticas colorrectales, se sabe poco acerca de las diferencias entre el recto y el colon del lado izquierdo.OBJETIVO:Este estudio evaluó el valor pronóstico de la ubicación del tumor primario en pacientes con metástasis hepáticas colorrectales examinando el recto y el colon del lado izquierdo por separado.DISEÑO:Este fue un estudio retrospectivo de 2003 a 2017.ENTORNO CLÍNICO:El estudio se llevó a cabo en un Hospital del Centro Nacional de Cáncer.PACIENTES:La cohorte del estudio incluyó a 489 pacientes con metástasis hepáticas colorrectales de cáncer de colon del lado derecho (n = 119, 24%), cáncer de colon del lado izquierdo (n = 251, 51%) o cáncer de recto (n = 119, 24%). %) que fueron sometidos a resección hepática.PRINCIPALES MEDIDAS DE VALORACIÓN:Los resultados primarios fueron la supervivencia sin recaídas y la supervivencia general.RESULTADOS:Las tasas de supervivencia sin recaída a cinco años para los pacientes con cáncer de colon derecho, cáncer de colon izquierdo y cáncer de recto fueron del 28,6%, 34,1%, y 26,4%, respectivamente, y las tasas de supervivencia general a los 5 años fueron del 53,9%, 70,3%, y 60,8%, respectivamente. El análisis multivariable reveló diferencias significativas en la supervivencia sin recaída y la supervivencia general entre el cáncer de colon izquierdo y el cáncer de recto (supervivencia sin recaída: HR = 1,37, p = 0,03; supervivencia general: HR = 1,49, p = 0,03) y entre el cáncer de colon izquierdo y el cáncer de colon del lado derecho (supervivencia libre de recaídas: HR = 1,39, p = 0,02; supervivencia global: HR = 1,60, p = 0,01), pero no entre el cáncer de colon del lado derecho y el cáncer de recto. En pacientes con recurrencia (n = 325), el cáncer de colon izquierdo tuvo la tasa de recurrencia en sitios múltiples más baja y la tasa de resección quirúrgica más alta por recurrencia (cáncer de colon izquierdo, 20%/46%; cáncer de colon derecho, 32%/30%; cáncer de recto, 26%/39%).LIMITACIONES:Este estudio fue de diseño retrospectivo.CONCLUSIONES:El cáncer de recto se asoció con una peor supervivencia sin recaída y una supervivencia general peor en comparación con el cáncer de colon izquierdo en pacientes con metástasis hepáticas colorrectales que se sometieron a resección hepática. Nuestros hallazgos sugieren que el colon y el recto del lado izquierdo deben considerarse entidades distintas en las metástasis hepáticas colorrectales. Consulte Video Resumen en http://links.lww.com/DCR/B882 . (Tradducción-Dr. Ingrid Melo ).