Is primary sidedness a prognostic factor in patients with resected colon cancer liver metastases (CLM)?

Marques, Márcio Carmona; Ribeiro, Héber S. C.; Costa, Wilson Luiz da; Jesus, Victor Hugo Fonseca de; Macêdo, Mariana Petaccia de; Diniz, Alessandro Landskron; Godoy, A.; Farias, Igor Correia de; Aguiar, Samuel; Riechelmann, Rachel; Begnami, María Dirlei; Coimbra, Felipe J. F.

doi:10.1002/jso.25048

Cited by 22 publications

(19 citation statements)

References 28 publications

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“…For example, a number of studies have demonstrated inferior oncological outcome in patients undergoing surgical resection of CRCLM with right-sided versus left-sided colonic primary tumours[ 8 - 10 ]. This has not been a consistent observation, and others have shown no clear association[ 11 , 12 ]. The aim of the present systematic review is to provide a summary of the available evidence on the impact of PTL on oncological outcomes in patients with CRCLM.…”

Section: Introductionmentioning

confidence: 79%

“…This finding is supported by Yamashita et al[ 26 ] found that r -CRCLM were independently associated with “minor pathological response” (defined as cancer cells accounting for ≥ 50% of residual cells), and were thus less sensitive to chemotherapy with worse RFS and OS. Interestingly, Marques et al[ 11 ] found that when selecting patients for CRCLM resection based on chemosensitivity, the survival disadvantage seen with r -CRCLM was eliminated. This suggests fundamental differences in tumour biology with the less chemosensitive phenotype more frequently seen with right-sided PTL and in turn associated with poorer survival.…”

Section: Discussionmentioning

confidence: 99%

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Impact of primary tumour location on colorectal liver metastases: A systematic review

Bingham¹,

Shetye²,

Suresh³

et al. 2020

WJCO

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BACKGROUND Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide. Despite significant advances in screening, surgical management and adjuvant therapies, average 5-year survival seldom exceeds 60% in most developed nations. Metastatic disease represents the primary cause of mortality in patients with CRC, and the liver is the most common location for distant tumour spread. Up to 25% of patients are found to have synchronous liver metastases at the time of diagnosis and a further 30%-40% will develop metachronous disease in the course of follow-up. It has been suggested that primary tumour location [right side versus left side, primary tumour location (PTL)] can influence oncological outcomes in this patient group and that this should be considered in prognostic models and therapeutic decision-making algorithms. This suggestion is not universally accepted and there have been conflicting reports in the literature to date. AIM To provide a comprehensive summary of the available evidence regarding the impact of PTL on oncological outcomes in patients with colorectal cancer liver metastases (CRCLM). METHODS MEDLINE, EMBASE and COCHRANE were searched for relevant publications using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Data on oncological outcomes was then extracted from full text articles that met the predefined inclusion criteria. RESULTS A total of 41 studies were identified that met predefined inclusion criteria for this review. In 21 out of 38 studies that provided data on overall survival, a statistically significant improvement in overall survival was reported in patients with left sided primary tumours. These studies included a total of 13897 patients compared with 4306 patients in the studies that did not show a significant difference. Eight studies noted a similar trend towards improved disease-free or progression-free survival. Several authors observed distinct patterns of relapse after treatment of hepatic metastases according to PTL; for example hepatic recurrence after treatment of CRCLM appears to occur more aggressively with right-sided CRC. CONCLUSION Taken together, the findings of the present review indicate that PTL may have a role as an independent prognostic factor when determining treatment and disease surveillance strategies in CRC. The mechanisms responsible for this variation remain poorly understood, but are likely to relate to molecular, histological and embryological differences, as well as inherent differences in therapeutic sensitivity.

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Section: Introductionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Impact of primary tumour location on colorectal liver metastases: A systematic review

Bingham¹,

Shetye²,

Suresh³

et al. 2020

WJCO

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“…Adam et al 30 Umeda et al 31 Huang et al 32 Mavros et al 33 Viganò et al 34 Connor et al 35 Eefsen et al 36 Schirripa et al 37 Norén et al 38 Sasaki et al 20 Shindoh et al 39 Amikura et al 40 Creasy et al 22 Dupré et al 41 Liang et al 43 Rhu et al 44 Sultana et al 45 Wang et al 46 Yamashita et al 21 Yamashita et al 21 Goto et al 47 Berardi et al 48 Cremolini et al 49 Engstrand et al 50 Goffredo et al 51 lmai et al 52 Koch et al 53 Laengle et al 54 Ledys et al 55 Liao et al 56 Lionti et al 57 Loosen et al 58 Makowiec et al 59 Margonis et al 60 Marques et al 24 Oshi et al 61 Palkovics et al 62 Shigematsu et al 63 Vallance et al 64 Wang et al 23 Wang et al 65 Zheng et al 66 Prediction interval 0·1 0 ·5 1 2 10…”

Section: Fig 2 Forest Plots Showing Impact Of Primary Tumour Locatiomentioning

confidence: 99%

“…Partelli et al 29 Connor et al 35 Eefsen et al 36 Schirripa et al 37 Sasaki et al 20 Shindoh et al 39 Amikura et al 40 Creasy et al 22 Heise et al 42 Wang et al 46 Yamashita et al 21 Yamashita et al 21 Goto et al 47 Berardi et al 48 Cremolini et al 49 lmai et al 52 Laengle et al 54 Ledys et al 55 Lionti et al 57 Margonis et al 60 Marques et al 24 Oshi et al 61 Shigematsu et al 63 Wang et al 23 Zheng et al 66…”

Section: Referencementioning

confidence: 99%

“…Several single centres have recently investigated the prognostic role of primary tumour location (PTL) in patients with CRLM receiving surgical resection. Some studies showed that right‐sided PTL was an independent predictor of poorer overall survival (OS) and disease‐free survival (DFS) after hepatectomy compared with left‐sided PTL, but others found no prognostic difference. Whether PTL could act as an effective prognostic parameter in patients with surgically treated CRLM is still controversial and needs further investigation.…”

Section: Introductionmentioning

confidence: 99%

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Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases

Wang

Zhang

Wang

et al. 2019

British Journal of Surgery

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Background Primary tumour location is emerging as an important prognostic factor in localized and metastatic colorectal cancers. However, its prognostic role in colorectal liver metastasis (CRLM) after hepatectomy remains controversial. A systematic review and meta‐analysis was undertaken to evaluate its prognostic value. Methods References were identified through searches of PubMed, Embase, Web of Science and the Cochrane Library comparing overall or disease‐free survival after hepatic resection between patients with CRLM originating from right‐ or left‐sided colorectal cancers. Data were pooled using hazard ratios (HRs) and 95 per cent confidence intervals according to a random‐effects model. Meta‐regression and subgroup analyses were conducted to assess the effect of underlying confounding factors on HR estimates and to adjust for this. Results The final analysis included 21 953 patients from 45 study cohorts. Compared with left‐sided primary tumour location, right‐sided location was associated with worse overall survival (HR 1·39, 95 per cent c.i. 1·28 to 1·51; P < 0·001; prediction interval 1·00 to 1·93), and also tended to have a negative impact on disease‐free survival (HR 1·18, 1·06 to 1·32; P = 0·004; prediction interval 0·79 to 1·75). Subgroup analysis showed that the negative effect of right‐sided primary tumour location on overall survival was more prominent in the non‐Asian population (HR 1·47, 1·33 to 1·62) than the Asian population (HR 1·18, 1·05 to 1·32) (P for interaction <0·01). Conclusion This study demonstrated a prognostic role for primary tumour location in patients with CRLM receiving hepatectomy, especially regarding overall survival. Adding primary tumour location may provide important optimization of prognosis prediction models for CRLM in current use.

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Prognostic value of the combination of primary tumor location and RAS mutational status on patients with colorectal liver metastasis undergoing hepatectomy

Yan

Wang

Bao

et al. 2022

Journal of Surgical Oncology

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Objective To assess prognostic influences of RAS mutational status and primary tumor site on cases with colorectal liver metastasis (CRLM) who underwent hepatectomy. Methods Clinicopathological data of 762 patients with CRLM who underwent hepatectomy between January 2000 and November 2018 were retrospectively analyzed. The left‐sided tumors (LST) included tumors located in the splenic flexure, descending colon, sigmoid colon, and rectum; while right‐sided tumors (RST) included those located in the cecum, ascending colon, and transverse colon. RAS mutational status was determined using Sanger sequencing or next‐generation sequencing, including KRAS (Codons 12, 13, and 61) and NRAS (Codons 12, 13, and 61), which were defined as wild‐type (RASwt) and mutant‐type (RASmut), respectively. Survival curves were plotted using the Kaplan–Meier plotter and compared by the log rank test. The clinicopathological data were analyzed using univariate and multivariate analyses. Results The 5‐year overall survival (OS) in the LST group was longer than that in the RST group (OS: 47.1% vs. 31.0%, p = 0.000, respectively), and the OS in the RASwt group was longer compared with that in the RASmut group (OS: 53.6% vs. 24.0%, p = 0.000). Besides, overall survival of the patients after hepatectomy was alternative, which was stratified by primary tumor site, with the 1‐, 3‐, and 5‐year survival rates of 93.1%, 62.1%, and 47.1% for patients with LST, and 91.1%, 42.8%, and 31.0% for patients with RST, respectively. OS and disease‐free survival (DFS) were significantly different stratified by RAS mutational status, with the 1‐, 3‐, and 5‐year rates of 96.9%, 67.9%, and 53.6% for patients with RASwt tumors, and 85.7%, 41.5%, and 24.0% for patients with RASmut tumors, respectively. The 1‐, 3‐, and 5‐year DFS rates were 51.9%, 30.0%, and 26.7% for patients with RASwt tumors, and 35.8%, 18.2%, and 14.9% for patients with RASmut tumors, respectively. The results of multivariate analysis showed that RAS mutational status and primary tumor site were both independent influencing factors of OS. Conclusion RAS mutational status and primary tumor site affect OS independently in CRLM patients undergoing hepatectomy. The worse prognosis of RST cannot be simply attributed to the imbalance of RAS mutational status in different primary tumor sites.

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Is primary sidedness a prognostic factor in patients with resected colon cancer liver metastases (CLM)?

Abstract: Sidedness do not seem to be a predictor of long term survival in patients with resected colon cancer liver metastases.

Cited by 22 publications

References 28 publications

Impact of primary tumour location on colorectal liver metastases: A systematic review

Impact of primary tumour location on colorectal liver metastases: A systematic review

Meta-analysis of the association between primary tumour location and prognosis after surgical resection of colorectal liver metastases

Prognostic value of the combination of primary tumor location and RAS mutational status on patients with colorectal liver metastasis undergoing hepatectomy

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