Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer

Nitsche, Ulrich; Stöß, Christian; Stecher, Lynne; Wilhelm, Dirk; Frieß, Helmut; Ceyhan, Güralp O.

doi:10.1002/bjs.10682

Cited by 24 publications

(18 citation statements)

References 82 publications

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“…The NCCN guidelines recommend surgery only in symptomatic patients, but non‐curative resection in asymptomatic patients has been advocated by different authors to prevent emergency procedures and some studies suggest a survival benefit when surgery is performed. On the other hand, colorectal surgery, in general, is associated with high morbidity rates which are even higher in patients with metastatic colorectal cancer . Postoperative complications may result in delayed adjuvant therapy or even precluding postoperative chemotherapy or radiation altogether, as noted by Hendren et al It is to be expected that with the improvements in chemotherapeutic agents, the number of surgical interventions should decline.…”

Section: Discussionmentioning

confidence: 99%

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The impact of postoperative morbidity on survival in patients with metastatic colon and rectal cancer

Leijssen

Dinaux

Kunitake

et al. 2019

Journal of Surgical Oncology

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Introduction: Avoiding postoperative morbidity is essential in patients with advanced cancer. To further improve treatment in stage IV colorectal cancer, knowledge about risk factors which effect short‐ and long‐term outcomes is important. Methods: All stage IV colon and rectal cancer who underwent elective surgery between 2004 and 2015 were included (n = 345). We compared resectable colon and rectal patients, and unresectable colon and rectal cancer patients. Results: Median follow‐up duration was 22.2 (unresectable) and 56.7 months (resectable) with no difference in tumor location. Colon cancer patients were more often considered unresectable (P < .001). Rectal procedures were correlated with a higher morbidity rate and a longer surgical duration (P < .001). In the resectable cohort, obese patients, open procedures and prolonged surgery were independently associated with postoperative complications. Considering the palliative group, neoadjuvant treatment and age were correlated with worse outcomes. Morbidity was not associated with long‐term outcomes in the resectable cohort. However, unresectable patients who developed respiratory (hazard ratio [HR]: 7.53) or cardiac (HR: 3.75) complications and patients with an American Society of Anesthesiologists—score III to IV (HR: 1.51) had an impaired survival. Conclusion: Our results emphasize the need for an adequate preoperative assessment to identify patients at risk for postoperative complications and impaired survival.

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Section: Discussionmentioning

confidence: 99%

“…Moreover, colon cancer patients were older with a significant difference in the resectable cohort (mean 59. 19 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24) .269 19 (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) 17 (14)(15)(16)(17)(18)(19)(20)(21) .082…”

Section: Baseline Characteristicsmentioning

confidence: 99%

The impact of postoperative morbidity on survival in patients with metastatic colon and rectal cancer

Leijssen

Dinaux

Kunitake

et al. 2019

Journal of Surgical Oncology

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“…In addition, a decrease in tumor burden after PTR is expected to increase the potential survival. Several retrospective studies and meta-analyses have reported survival benefits of PTR compared with upfront chemotherapy [ 3 , 4 , 5 ]. According to the analysis of the Surveillance, Epidemiology, and End Results (SEER) database by Tarantino et al [ 6 , 7 ], PTR results in prolonged overall and cancer-specific survival compared to upfront chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

The Role of Primary Tumor Resection in Colorectal Cancer Patients with Asymptomatic, Synchronous, Unresectable Metastasis: A Multicenter Randomized Controlled Trial

Park

Baek

Choi

et al. 2020

Cancers

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We aimed to assess the survival benefits of primary tumor resection (PTR) followed by chemotherapy in patients with asymptomatic stage IV colorectal cancer with asymptomatic, synchronous, unresectable metastases compared to those of upfront chemotherapy alone. This was an open-label, prospective, randomized controlled trial (ClnicalTrials.gov Identifier: NCT01978249). From May 2013 to April 2016, 48 patients (PTR, n = 26; upfront chemotherapy, n = 22) diagnosed with asymptomatic colorectal cancer with unresectable metastases in 12 tertiary hospitals were randomized (1:1). The primary endpoint was two-year overall survival. The secondary endpoints were primary tumor-related complications, PTR-related complications, and rate of conversion to resectable status. The two-year cancer-specific survival was significantly higher in the PTR group than in the upfront chemotherapy group (72.3% vs. 47.1%; p = 0.049). However, the two-year overall survival rate was not significantly different between the PTR and upfront chemotherapy groups (69.5% vs. 44.8%, p = 0.058). The primary tumor-related complication rate was 22.7%. The PTR-related complication rate was 19.2%, with a major complication rate of 3.8%. The rates of conversion to resectable status were 15.3% and 18.2% in the PTR and upfront chemotherapy groups. While PTR followed by chemotherapy resulted in better two-year cancer-specific survival than upfront chemotherapy, the improvement in the two-year overall survival was not significant.

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“…Human colorectal cancer (CRC) is the second leading cause of cancer death in the US, and~25% of patients with CRC are incurable at the time of diagnosis [1,2]. Genetic heterogeneity is inherent to this disease, providing tumor cells with the ability to rapidly adapt and resist treatments [3,4].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic loss of heterozygosity of Apc and an inflammation-associated mutational signature detected in Lrig1+/−-driven murine colonic adenomas

Preston

Stiffler

2020

BMC Cancer

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Background: The loss of a single copy of adenomatous polyposis coli (Apc) in leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1)-expressing colonic progenitor cells induces rapid growth of adenomas in mice with high penetrance and multiplicity. The tumors lack functional APC, and a genetic loss of heterozygosity of Apc was previously observed. Methods: To identify genomic features of early tumorigenesis, and to profile intertumoral genetic heterogeneity, tumor exome DNA (n = 9 tumors) and mRNA (n = 5 tumors) sequences were compared with matched nontumoral colon tissue. Putative somatic mutations were called after stringent variant filtering. Somatic signatures of mutational processes were determined and splicing patterns were observed. Results: The adenomas were found to be genetically heterogeneous and unexpectedly hypermutated, displaying a strong bias toward G:C > A:T mutations. A genetic loss of heterozygosity of Apc was not observed, however, an epigenetic loss of heterozygosity was apparent in the tumor transcriptomes. Complex splicing patterns characterized by a loss of intron retention were observed uniformly across tumors. Conclusion: This study demonstrates that early tumors originating from intestinal stem cells with reduced Lrig1 and Apc expression are highly mutated and genetically heterogeneous, with an inflammation-associated mutational signature and complex splicing patterns that are uniform across tumors.

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Meta-analysis of outcomes following resection of the primary tumour in patients presenting with metastatic colorectal cancer

Abstract: Primary tumour resection may provide a modest survival advantage in patients presenting with metastatic colorectal cancer.

Cited by 24 publications

References 82 publications

The impact of postoperative morbidity on survival in patients with metastatic colon and rectal cancer

The impact of postoperative morbidity on survival in patients with metastatic colon and rectal cancer

The Role of Primary Tumor Resection in Colorectal Cancer Patients with Asymptomatic, Synchronous, Unresectable Metastasis: A Multicenter Randomized Controlled Trial

Epigenetic loss of heterozygosity of Apc and an inflammation-associated mutational signature detected in Lrig1+/−-driven murine colonic adenomas

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