The impact of primary tumor resection for asymptomatic colorectal cancer patients with unresectable metastases: a systematic review and meta-analysis.

BACKGROUND: Whether patients with asymptomatic primary tumors and unresectable metastases of colorectal cancer (CRC) should undergo primary tumor resection (PTR) remains controversial. This study aims to determine the appropriateness of PTR for these individuals by evaluating a number of outcome measures. METHODS: A systematic literature search was performed. Outcome measures included overall survival, emergency surgery rates, incidence of postoperative complications, time to initiate chemotherapy, conversion rates, and chemotherapy-related toxicities. RESULTS: Patients who received PTR in addition to chemotherapy had a better overall survival rate than those who only received chemotherapy (HR = 0.62, 95%CI, 0.50-0.78, I2 = 84%, p < 0.00001). In the RCT subgroup, there were no significant differences with a HR of 0.72 (95%CI, 0.45-1.13, I2 = 17%, p = 0.15). More patients in the chemotherapy alone group could be converted to resectable status (OR = 0.47, 95%CI, 0.27-0.82, I2 = 0%, p = 0.008), but the incidence of emergency surgery was 23% (95%CI, 17-29%, I2 = 14%). The risk of chemotherapy-related toxicity was not significantly higher in the PTR group (OR = 1.5, 95%CI, 0.94-2.43, p = 0.09, I2 = 0%), with a 7% incidence of postoperative complications (95%CI, 0-14%, p = 0.05, I2 = 0%). The time to initiate chemotherapy after PTR was approximately 33.06 days (95%CI, 25.55-40.58, I2 = 0%). CONCLUSION: PTR plus chemotherapy may be associated with improved survival in asymptomatic CRC patients with unresectable metastases. However, PTR did not provide a significant survival benefit in the subgroup of RCTs. Additionally, PTR did not result in a significantly increased risk of chemotherapy-related toxicity, with a postoperative complication rate of approximately 7%, and chemotherapy could be initiated at approximately 33.06 days after PTR. Compared with the PTR plus chemotherapy, chemotherapy alone could result in a significantly higher conversion rate. However, about 23% of patients receiving chemotherapy alone required emergency surgery for primary tumor-related symptoms. The above results needed to be validated in future larger prospective randomized trials.

[Colorectal cancer liver metastases: current state of the problem, priority treatment approaches]. / Metastazy kolorektal'nogo raka v pechen': sovremennoe sostoyanie problemy, prioritetnye podkhody v lechenii.

The review is devoted to the world trends in epidemiology of colorectal cancer and treatment of colorectal cancer liver metastases. The authors analyze the effectiveness of traditional (resection) and modern minimally invasive methods of local destruction (radiofrequency thermoablation, microwave ablation, cryoablation), stereotactic radiotherapy, radiosurgery, targeted therapy and endovascular techniques (chemoinfusion, chemoembolization, radioembolization). It was emphasized that searching for new chemotherapeutic and targeted drugs is one of the reserve ways to improve treatment outcomes in patients with potentially resectable colorectal cancer liver metastases. The possibilities and prospects of liver transplantation as a priority treatment strategy for patients with unresectable bilobar colorectal cancer liver metastases are highlighted.

Risk factors for the requirement of surgical or endoscopic interventions during chemotherapy in patients with uncomplicated colorectal cancer and unresectable synchronous metastases.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the risk factors for requirement of surgical or endoscopic interventions for complications caused by the primary tumor during chemotherapy in patients with unresectable metastatic colorectal cancer. METHODS: A total of 259 patients were diagnosed with uncomplicated colorectal cancer with unresectable metastatic disease and underwent chemotherapy as an initial treatment. Among them, 57 (22.0%) patients underwent palliative interventions because of complications caused by the primary tumor during chemotherapy, including bypass surgery or diverting enterostomy for 22 patients, insertion of colonic stent for 22, and resection of primary tumor for 13. RESULTS: Multivariate analysis revealed that rectal lesion (RR, 2.132; 95% CI, 1.080-4.210; P = 0.029) and tumor size larger than 5 cm (RR = 3.644, 95% CI = 1.923-6.902; P < 0.001) were significant risk factors for requirement of palliative intervention. Patients who had none of the risk factors showed better overall survival than those who had one or more (P = 0.021). CONCLUSIONS: Tumor location in rectum and tumor size larger than 5 cm were significant risk factors for the requirement of surgical or endoscopic interventions during chemotherapy for complications caused by the primary tumor in patients with unresectable metastatic colorectal cancer.

Hepatic arterial infusion pump chemotherapy in the management of colorectal liver metastases: expert consensus statement.

Despite significant improvements in systemic therapy for patients with colorectal liver metastases (crlms), response rates in the first-line setting are not optimal, and response rates in the second-line setting remain disappointing. Hepatic arterial infusion pump (haip) chemotherapy has been extensively studied in patients with crlms, but it remains infrequently used. We convened an expert panel to discuss the role of haip in the contemporary management of patients with crlm. Using a consensus process, we developed these statements: haip chemotherapy should be given in combination with systemic chemotherapy.haip chemotherapy should be offered in the context of a multidisciplinary program that includes expertise in hepatobiliary surgery, medical oncology, interventional radiology, nursing, and nuclear medicine.haip chemotherapy in combination with systemic therapy should be considered in patients with unresectable crlms who have progressed on first-line systemic treatment. In addition, haip chemotherapy is acceptable as first-line treatment in patients with unresectable colorectal liver metastases.haip chemotherapy is not recommended in the setting of extrahepatic disease outside the context of a clinical trial.haip chemotherapy in combination with systemic therapy is an option for select patients with resected colorectal liver metastases. These consensus statements provide a framework that clinicians who treat patients with crlm can use when considering treatment with haip.

[Treatment of colorectal cancer with unresectable metastasis with chemotherapy without primary tumor resection: analysis of tumor-related complications]. / Tratamiento del cáncer colorrectal con metástasis irresecables con quimioterapia sin resección del primario: análisis de las complicaciones relacionadas con el tumor.

INTRODUCTION: Although the conventional treatment of patients with stage iv colorectal cancer involves resection of the primary tumor followed by chemotherapy, several studies suggest that in patients with few symptoms the first and only treatment should be chemotherapy. The objective of this study is to analyze the complications related to the primary tumor in a series of patients with unresectable metastatic colorectal cancer treated with chemotherapy without surgery. MATERIAL AND METHODS: Retrospective descriptive study. The study included all patients with unresectable metastatic colorectal cancer treated with chemotherapy without resection of the primary tumor (January 2007-February 2011). RESULTS: The mean age of the 61 patients analyzed was 67±13 years and the performance status was 0-1 in 53 (87%). Twenty (33%) patients developed complications during follow-up. The most common complication was intestinal obstruction in 15 (25%) patients followed by perforation. Complications required surgery in 6 (10%) cases. We did not find differences in patient characteristics between those who had a complication and those without, although the complication rate in patients with a colonic stent (53%) was twice that of other patients (26%). CONCLUSIONS: Chemotherapy without surgery is a good option in most patients with unresectable metastatic colorectal cancer. However, although the percentage of patients requiring surgery is low, the total number of complications related to the primary tumor is not negligible. Studies are needed to identify those patients in whom a prophylactic colectomy could be indicated.

The Safety and Effectiveness of Bevacizumab in Metastatic Colorectal Cancer With Unresectable Metastases: A Real-Life Study From the South of Morocco.

Background Colorectal cancer constitutes a significant public health challenge, despite remarkable strides made in the last two decades, particularly in the medical management of metastatic stages. Notable progress has been achieved through targeted therapies such as anti-epidermal growth factor receptors or anti-angiogenic antibodies, as well as advancements in surgical approaches for hepatic metastases. This study seeks to assess the efficacy and safety of bevacizumab plus chemotherapy in individuals with metastatic colorectal cancer. Methodology This is an observational, cross-sectional, retrospective study of all patients who were followed up for metastatic colorectal cancer with unresectable metastases and were treated with bevacizumab in combination with standard chemotherapy from January 2010 until December 2019 in the medical oncology department of the Centre Hospitalier Universitaire (CHU) Souss-Massa of Agadir. Results Of the total 162 cases, 117 (72%) had metastatic disease, and 45 (28%) progressed to metastatic disease after initial treatment. The median age of the patients was 55 years (range = 23-79 years) with a sex ratio of 1.1 (M/F). The tumor was located in the left colon in 135 (83.3%) patients. The results represented adenocarcinoma in 137 (84.6) cases and mucinous subtype in 23 (14.19) cases. The three most common sites of metastasis were the liver (99, 61.1), peritoneum (67, 41.3), and lung (33, 20.3). In the first line, all patients received bi-chemotherapy plus bevacizumab, i.e., fluorouracil, oxaliplatin, and leucovorin in 34 (20.9%) patients; capecitabine plus oxaliplatin in 88 (54.3%) patients; leucovorin, fluorouracil, and irinotecan in 17 (10.4%) patients; and capecitabine plus irinotecan in 23 (14.1%) patients. Response after first-line treatment was progression in 74 (45.7) cases, stability in 42 (25.9) cases, partial response in 35 (21.6) cases, and complete response in 11 (6.8) cases. Nine (6%) patients were able to benefit from surgical resection of metastatic lesions. Overall, 77 (47%) patients received second-line chemotherapy, i.e., 5-FU with irinotecan in 40 (51.8%) cases or with oxaliplatin in 30 (38.8%) cases. Two patients developed undesirable side effects under bevacizumab (hypertension). The median progression-free survival and median overall survival of the study cohort were 9 months and 14 months, respectively. Nevertheless, patients who underwent primary tumor resection (p = 0.048), those with right­sided tumors (p = 0.022), those who received a higher number of treatment cycles (p = 0.020), and those who received maintenance treatment (p = 0.001) had a longer median overall survival. Conclusions Chemotherapy combination with bevacizumab is considered as the cornerstone of metastatic colorectal cancer treatment in our region. With the new healthcare and social security systems, easier access to expensive treatments and molecular pathology tests is currently available. It is important to highlight that real-world data can offer valuable insights into the daily clinical practice of medical oncology.

Induction Chemotherapy Followed by Primary Tumor Resection Did Not Bring Survival Benefits in Colon Cancer Patients With Asymptomatic Primary Lesion and Synchronous Unresectable Metastases.

BACKGROUND: It is still controversial whether primary tumor resection (PTR) improves survival in colorectal cancer (CRC) patients with unresectable metastases. METHODS: Colon cancer patients were enrolled and randomly allocated to with or without PTR after induction chemotherapy with XELOX or mFOLFOX6, and those with chemotherapy failure were excluded. The primary endpoint was TTF (time to strategy failure) on an intent-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02291744. RESULTS: Between April 2015 and July 2020, 140 patients were enrolled, and 54 patients were excluded due to colon obstruction (16), perforation (1), disease progression (22), death (1), radical resection (3), or other reasons (11). After induction chemotherapy, 86 patients were randomized into group A (the resection group, n = 42) or group B (chemotherapy-alone group, n = 44). The median TTF was 143 days (95% CI: 104.9-181.1) in group A and 196 days (95% CI: 96.5-295.5) in group B (HR: 0.930 95% CI: 0.589-1.468, p = 0.755), and there was no significant difference in PFS, OS, and incidence of chemotherapy-related adverse events between two groups. The primary lesion-related events after PTR in group A were significantly fewer than those in group B. Patients with a tumor regression grade (TRG) score of 2 had longer TTF and PFS than those with score of 3. CONCLUSION: PTR after induction chemotherapy could not bring survival benefits for colon cancer patients with unresectable metastases, and it is not recommended routinely. However, it also requires individualized treatment as colon obstruction or perforation occurred in some patients and PTR could reduce primary tumor-related events, and the TRG score might help for selection of beneficial patients.

Impact of Upfront Chemotherapy on the Effect of Primary Tumour Resection for Asymptomatic Synchronous Colorectal Cancer With Unresectable Metastases: A Propensity-Score-Matched Cohort Analysis.

Background: It is controversial whether primary tumour resection (PTR) and the sequencing of chemotherapy and PTR are associated with the survival of patients with incurable stage IV colorectal cancer. This study aimed to explore the effects of PTR and the sequencing of chemotherapy and PTR on asymptomatic colorectal cancer with synchronous unresectable metastases (asmCRC). Patients and Methods: Patients with asmCRC were retrospectively identified from a single centre and categorised into 3 groups: PTR followed by chemotherapy (POC), upfront chemotherapy followed by PTR (UFC), and palliative chemotherapy (PC). The primary end points included median overall survival (OS) and progression-free survival (PFS). Clinical features were analysed using χ2 test, while survival curves were generated using the Kaplan-Meier test. Propensity-score matching (PSM) was performed when comparing survival between POC and UFC groups. Results: From 2008 to 2014, 255 patients were identified and included into the POC (n = 101), UFC (n = 40), and PC (n = 114) groups. The UFC and POC groups had significantly better median OS compared with the PC group (40.7 vs 16.3 months, P < .0001; 39.7 vs 16.3 months, P < .0001). Before PSM, the UFC group had better median PFS than the POC and PC groups (18.5 vs 9.7 months, P = .038; 18.5 vs 6.1 months, P < .0001). After PSM, UFC has better PFS than POC (P = .038). And the UFC group did not have higher postoperative or preoperative morbidity compared with the POC group (P = .235). Conclusions: Primary tumour resection could improve the survival of patients with asmCRC. Compared with POC or PC, UFC was associated with a better median PFS without significantly increasing preoperative or postoperative morbidity.

Successful Conversion Surgery for Advanced Gastric Cancer With Multiple Liver Metastases Following Ramucirumab Plus Paclitaxel Combination Treatment.

AIM: To present the case of a patient with unresectable gastric cancer showing a remarkable effect by second-line drug treatment with ramucirumab plus paclitaxel and conversion surgery. CASE REPORT: A 68-year-old woman who was diagnosed with gastric cancer was referred to us. Esophagogastroduodenoscopy showed an ulcerated lesion with an irregular nodulated border in the lower third of the stomach, and histology of biopsied specimens indicated a poorly differentiated adenocarcinoma. Enhanced computed tomography revealed extensive invasion of the liver, and the patients was treated using S-1 plus oxaliplatin as first-line chemotherapy. Because she developed liver metastases, the treatment regimen was changed to ramucirumab plus paclitaxel as the second-line treatment. After four cycles of weekly paclitaxel with ramucirumab treatment, the liver metastases had completely disappeared. Because no other metastatic lesions in other organs were detected, we performed total gastrectomy with D2 lymphadenectomy. The macroscopic findings of the surgically resected specimen revealed an ulcerated lesion with an irregularly modulated lesion measuring 9.5×4.5 cm. Pathological analysis demonstrated a poorly differentiated adenocarcinoma in the stomach, with invasion to the liver through the serosal layer, and seven lymph node metastases. The postoperative course was unremarkable, and she received ramucirumab in combination with paclitaxel treatment. However, liver metastasis appeared at 4 months after the operation, for which she was treated with irinotecan. Although the patient continued to receive irinotecan chemotherapy for 10 months, her general condition gradually deteriorated, and she was started on best supportive care 13 months after conversion surgery. CONCLUSION: Conversion surgery may prolong survival not only through first-line but also second-line treatments in selected patients with unresectable advanced gastric cancer; however, assessments of additional cases and further studies are required to establish this treatment strategy.

Management of asymptomatic primary tumours in stage IV colorectal cancer: Review of outcomes.

AIM: To compare outcomes for patients presenting with stage IV colorectal cancer and an asymptomatic primary tumour, undergoing primary tumour resection (PTR) plus palliative chemotherapy vs primary chemotherapy up-front. METHODS: A literature search was conducted using MEDLINE and EMBASE. The primary outcome was overall survival. Secondary outcomes included perioperative mortality, morbidity and delayed surgical intervention rates in patients undergoing PTR and subsequent complication rates in patients with an un-resected primary tumour. Tertiary outcomes included impact on systemic treatment and identification of prognostic factors relevant for survival in this cohort. RESULTS: Twenty non-randomised studies met the inclusion criteria. Eleven studies included comparative overall survival data. Three studies showed an overall survival advantage for PTR, 7 studies showed no statistically significant advantage, and 1 study showed a significant worsening in survival in the surgical group. The perioperative mortality rate ranged from 0% to 8.5%, and post-operative morbidity rate from 10% to 35%, mainly minor complications that did not preclude subsequent chemotherapy. The rate of delayed primary-tumour related symptoms, most commonly obstruction, in patients with an un-resected primary tumour ranged from 3% to 46%. The strongest independent poor prognostic factor was extensive hepatic metastases, in addition to poor performance status, M1b stage and non-use of modern chemotherapy agents. CONCLUSION: Based on the current literature, both PTR and up front chemotherapy appear appropriate initial management strategies, with a trend towards an overall survival advantage with PTR. The procedure has a low post-operative mortality, and most complications are transient and minor. The results of recruiting randomised trials are eagerly anticipated.

The Role of Surgery for Asymptomatic Primary Tumors in Unresectable Stage IV Colorectal Cancer.

There are still debates regarding the appropriate primary treatment policy for asymptomatic primary colorectal lesions in cases of unresectable metastatic colorectal cancer. Even though there are patients with asymptomatic primary tumors when starting chemotherapy, those patients may still undergo surgery due to complications related to primary tumors in the middle of chemotherapy; therefore, controversy exists regarding surgical resection of primary colorectal lesions in cases where symptoms are absent when making a diagnosis. Thus, based on the published literature, we discuss opinions that prefer first-line surgery for primary tumors as well as opinions favoring first-line chemotherapy for treating unresectable synchronous metastatic colorectal cancer. Although the upfront chemotherapy including targeted agents is suggested as an effective treatment in recent years, the first line surgery has been a preferred treatment for decades. The first line surgery is beneficial to prolong the survival duration given the retrospective analysis of randomized trial data. So far, no prospective comparison study has only focused on the first-line treatment modality; thus, future clinical studies focusing on the survival duration and the quality of life should be performed as soon as possible. Furthermore, at this point, multidisciplinary team approaches would be helpful in finding the appropriate therapy. Regardless of symptoms, the performance status and the tumor burden should be taken into consideration as well. In case of surgical resection, minimally invasive surgery, such as laparoscopic surgery, is recommended.

The Role of Surgery for Asymptomatic Primary Tumors in Unresectable Stage IV Colorectal Cancer

There are still debates regarding the appropriate primary treatment policy for asymptomatic primary colorectal lesions in cases of unresectable metastatic colorectal cancer. Even though there are patients with asymptomatic primary tumors when starting chemotherapy, those patients may still undergo surgery due to complications related to primary tumors in the middle of chemotherapy; therefore, controversy exists regarding surgical resection of primary colorectal lesions in cases where symptoms are absent when making a diagnosis. Thus, based on the published literature, we discuss opinions that prefer first-line surgery for primary tumors as well as opinions favoring first-line chemotherapy for treating unresectable synchronous metastatic colorectal cancer. Although the upfront chemotherapy including targeted agents is suggested as an effective treatment in recent years, the first line surgery has been a preferred treatment for decades. The first line surgery is beneficial to prolong the survival duration given the retrospective analysis of randomized trial data. So far, no prospective comparison study has only focused on the first-line treatment modality; thus, future clinical studies focusing on the survival duration and the quality of life should be performed as soon as possible. Furthermore, at this point, multidisciplinary team approaches would be helpful in finding the appropriate therapy. Regardless of symptoms, the performance status and the tumor burden should be taken into consideration as well. In case of surgical resection, minimally invasive surgery, such as laparoscopic surgery, is recommended.