Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY

Sekiguchi, Masau; Takeuchi, Yoji; Tanaka, Shinji; Yamamoto, Hironori; Shinmura, Kensuke; Harada, Kaori; Uraoka, Toshio; Hisabe, Takashi; Sano, Yasushi; Kondo, Hitoshi; Horimatsu, Takahiro; Kikuchi, Hidezumi; Kawamura, Takuji; Nagata, Shinji; Yamamoto, Katsumi; Tajika, Masahiro; Tsuji, Shigetsugu; Kusaka, Toshihiro; Okuyama, Yûsuke; Yoshida, Naohisa; Moriyama, Tomohiko; Hasebe, Aki; So, Suketo; Kobara, Hideki; Kashida, Hiroshi; Miyanaga, Ryoichi; Kato, Sosuke; Hayashi, Yoshito; Sada, Miwa; Fukuzawa, Masakatsu; Kato, Hiroyuki; Takayama, Tetsuji; Konishi, Jun; Matsushita, Hirokazu; Narasaka, Toshiaki; Ohata, Ken; Togashi, Kazutomo; Nakamura, Hisashi; Moriichi, Kentaro; Oda, Yasushi; Kanda, Naoki; Kuwai, Toshio; Terai, Shuji; Sanomura, Makoto; Kitamura, Shinji; Miyamoto, Hayato; Kiriyama, Shinsuke; Mizuno, Chiemi; Saito, Yutaka; Sekine, Shigeki; Ito, Sayo; Nakahira, Hiroko; Oka, Shiro; Hayashi, Yoshikazu; Yoshimura, Kenichi; Ishikawa, Hideki; Matsuda, Takahisa

doi:10.1007/s00535-022-01877-5

Cited by 11 publications

(10 citation statements)

References 27 publications

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“…In a study that included 9926 NENs of the colon and rectum from the Surveillance, Epidemiology, and End Results (SEER) database, Ding et al found that only 1092 (11.0%) individuals suffered from metastatic disease; however, in a subgroup analysis, metastatic disease developed in 3.6% and 41.1% of patients with well-differentiated NETs and poorly differentiated NECs, respectively [ 10 ]. Another report from the C-NET study, a Japanese multicenter prospective study of colorectal NETs, included 500 colorectal NETs, and only 3 (0.6%) of them presented metastatic disease [ 18 ]. However, most previous studies have shown that more than half of colorectal NECs have distant metastases at the date of initial diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Tumor Differentiation is the Dominant Prognostic Factor for Patients with Colorectal Neuroendocrine Neoplasms with Distant Metastasis

Wang

Shi

Ren

et al. 2022

International Journal of Endocrinology

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Purpose. Colorectal neuroendocrine neoplasms (NENs) are rare tumors. The prognosis and prognostic factors of metastatic colorectal NENs have not been fully elucidated. Methods. We retrospectively enrolled 77 consecutive patients diagnosed with colorectal NENs with synchronous distant metastases between 2000 and 2021. All patients were assigned to the neuroendocrine tumor (NET) group or the neuroendocrine carcinoma (NEC) group based on histological differentiation. Propensity score matching (PSM) was performed to minimize confounding bias. The Kaplan–Meier method was used to calculate the survival rates. Univariate and multivariate logistic regression analyses were performed to identify prognostic factors. Results. In total, 35 (45.5%) and 42 (54.5%) patients had well-differentiated NETs and poorly differentiated NECs, respectively. The median overall survival (OS) was 26 months for the entire cohort, and the 1-year, 3-year, and 5-year OS rates were 69.4%, 41.4%, and 27.8%, respectively. In the subgroup analysis, the median OS was 62 and 10 months for NETs and NECs, respectively. Univariate analysis demonstrated that patients with a primary tumor located in the colon, ulcerative tumors and poorly differentiated tumors were at higher risk for poorer progression-free survival (PFS) and OS. However, only histological differentiation was identified as an independent factor affecting OS (hazard ratio (HR) = 8.28, 95% confidence interval (CI): 2.98–23.01, P < 0.001 ) in multivariate analysis. After PSM, histological differentiation was further confirmed as the dominant factor affecting OS (HR = 6.09, 95% CI: 1.96–18.95, P = 0.002 )). Conclusion. Histological differentiation was the most dominant prognostic factor in patients with metastatic colorectal NENs. Patients with well-differentiated NETs had a good chance of long-term survival.

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Section: Discussionmentioning

confidence: 99%

Tumor Differentiation is the Dominant Prognostic Factor for Patients with Colorectal Neuroendocrine Neoplasms with Distant Metastasis

Wang

Shi

Ren

et al. 2022

International Journal of Endocrinology

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“…A 10-year follow-up is planned, and the results are worthy of attention. [6] For local excision, good results have been reported in transanal surgery. The advantage is that full-thickness resection is possible, and safe surgical outcomes have been reported, including in those with large tumor diameters.…”

Section: Methodsmentioning

confidence: 99%

“…[1] Meanwhile, in Japan, South Korea, China, and Taiwan, the rectum is the most common site of occurrence. [3–6]…”

Section: Introductionmentioning

confidence: 99%

“…[1] Meanwhile, in Japan, South Korea, China, and Taiwan, the rectum is the most common site of occurrence. [3][4][5][6] The increase in the number of colonoscopies for colorectal cancer screening and the improvement of endoscopic equipment and technology have contributed to the increase in rectal NENs, especially G1/G2 well-differentiated neuroendocrine tumors (NETs). [7,8] However, it has been reported that NETs and positive resection margins are often found on histopathological examination after the tumors are misidentified as colorectal polyps and managed with normal polypectomy.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of localized well-differentiated rectal neuroendocrine tumors: A focused review

et al. 2023

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The frequency of rectal neuroendocrine tumors increases with the increase in the number of colonoscopies performed for colorectal cancer screening. The treatment of localized rectal well-differentiated neuroendocrine tumors involves local excision, including endoscopic treatment or rectal resection with lymphadenectomy. Although it is important to determine the risk of lymph node metastasis, there are points of disagreement among the guidelines regarding surgical indications. In this review, we discuss the current status of the treatment of well-differentiated rectal neuroendocrine tumors. The PubMed database was searched for relevant studies. In Japan, the criteria for curative endoscopic resection are very strict: less than 10 mm, G1, no invasion of the muscularis propria, no suspicion of lymph node metastasis, and no lymphovascular invasion. Meanwhile, in Western guidelines, local excision (endoscopic treatment is preferable) is recommended as the initial treatment for tumors measuring ≥10 mm and <20 mm in diameter, and radical surgery is recommended for tumors ≥20 mm in diameter. There are still many points where evidence is lacking, and future research is warranted.

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“… 32 , 33 , 34 , 35 , 36 Furthermore, a recent Japanese multicenter prospective study on colorectal NETs, the details described later, has proven high positivity of lymphovascular invasion in colorectal NETs based on the assessment of prospectively enrolled colorectal NET patients. 37 There is a potential that follow‐up without secondary treatment for colorectal NETs with positive lymphovascular invasion can be a feasible management option when they do not have any other metastatic risk factors; however, more evidence is necessary.…”

Section: Management Following Local Resection Of Colorectal Netmentioning

confidence: 99%

Treatment strategy and post‐treatment management of colorectal neuroendocrine tumor

2023

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Following the increase in colorectal neuroendocrine tumors (NETs), there is a consequent increase in the importance of their appropriate treatment and post‐treatment management. It is widely accepted that colorectal NETs sized ≥20 mm and those with muscularis propria invasion are indicated for radical surgery, and those sized <10 mm without the invasion are indicated for local resection. No consensus has been reached regarding the treatment strategy for those sized 10–19 mm without the invasion. Endoscopic resection has become a primary option for the local resection of colorectal NETs. For rectal NETs sized <10 mm, modified endoscopic mucosal resection, such as endoscopic submucosal resection with ligation device and endoscopic mucosal resection with a cap‐fitted panendoscope, seems favorable because of its ability to achieve a high R0 resection rate, safety, and convenience. Endoscopic submucosal dissection can also be helpful for these lesions; however, this procedure may be more effective for large lesions or those in the colon. Management following local resection of colorectal NETs is based on the pathological evaluation of factors associated with metastasis, including tumor size, invasion depth, tumor cell proliferative activity (NET grading), presence of lymphovascular invasion, and resection margins. There remain unclear issues in managing cases with NET grading ≥2, positive lymphovascular invasion, and positive resection margins following local resection. In particular, there is confusion regarding managing positive lymphovascular invasion because positivity has become remarkably high with the increased use of the immunohistochemical/special staining. Further evidence based on long‐term clinical outcomes is required to address these issues.

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Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY

Cited by 11 publications

References 27 publications

Tumor Differentiation is the Dominant Prognostic Factor for Patients with Colorectal Neuroendocrine Neoplasms with Distant Metastasis

Tumor Differentiation is the Dominant Prognostic Factor for Patients with Colorectal Neuroendocrine Neoplasms with Distant Metastasis

Treatment of localized well-differentiated rectal neuroendocrine tumors: A focused review

Treatment strategy and post‐treatment management of colorectal neuroendocrine tumor

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