Asymptomatic primary tumour in incurable metastatic colorectal cancer: is there a role for surgical resection prior to systematic therapy or not?

Abstract

IntroductionThe role of the resection of asymptomatic primary colorectal cancer in patients with incurable disease is questionable.AimTo evaluate the impact of the resection of asymptomatic primary tumour on overall survival in patients with unresectable distant metastases.Material and methodsPatients treated in the National Cancer Institute, Lithuania, in the period 2008–2012, were selected retrospectively. The main inclusion criteria were: metastatic colorectal cancer (mCRC), endoscopically and histologically confirmed adenocarcinoma, without any symptoms for urgent operation, and at least one cycle of palliative chemotherapy administered. Information on patients’ age, gender, tumour histology, localization of the tumour, regional lymph node involvement, number of metastatic sites, surgery and systemic treatment was collected prospectively. Eligible patients for the study were divided into two groups according to the initial treatment – surgery (patients who underwent primary tumour resection) and chemotherapy (patients who received chemotherapy without surgery). The impact of initial treatment strategy, tumour size and site, regional lymph nodes, grade of differentiation of adenocarcinoma and application of biotherapy on overall cumulative survival was estimated using the Kaplan-Meier method. To compare survival between groups the log-rank test was used. Cox regression analysis was employed to assess the effects of variables on patient survival.ResultsThe study group consisted of 183 patients: 103 men and 80 women. The median age was 66 years (range: 37–91). There were no notable imbalances with regard to age, gender, number of metastatic sites, metastases (such as pulmonary, peritoneal, liver, metastases into non-regional lymph nodes and other metastases), the number of received cycles of chemotherapy, first line chemotherapy type or biological therapy. Only 27 (14.8%) patients received biological therapy and the majority of them (n = 25, 92.6%) were treated with bevacizumab. For surgically treated patients 1-year survival was 71.2% (95% CI: 62.1–78.5) and 5-year survival was 4.0% (95% CI: 1.0–10.5). In the chemotherapy group, survival rates were lower – 43.9% (95% CI: 31.4–55.7) and 1.7% (95% CI: 0.1–8.1), respectively. Better survival rates were in the palliative surgery group. Multivariate analysis using the Cox proportional hazards model revealed that the initial palliative surgery and the application of biological therapy were statistically significant independent prognostic factors for survival.ConclusionsOur findings suggest that palliative resectional surgery for the primary tumour in patients with incurable mCRC improves survival. Of course, one can argue that patients in the surgery group were “less problematic”. Prospective randomized trials are needed to delineate precisely the role of palliative surgery of the primary tumour in these patients.

Primary Tumor Resection in Patients with Incurable Localized or Metastatic Colorectal Cancer: A Systematic Review and Meta‐analysis

“…Figure 1 shows the study flow diagram. Seventy‐seven comparative studies fulfilled the inclusion criteria of this meta‐analysis [2, 4–8, 10–27, 30–50, 69–100]. There were 159,991 patients for analysis, including 94,745 (59.2%) in the PTR group and 65,246 (40.8%) in the PTI group.…”

“…Nevertheless, not every patient will be a candidate for surgery, and among patients, the benefits of surgery will be different. Studies which performed multivariate analysis to determine which factors were associated with survival in patients with unresectable colorectal cancer, in addition to PTR, identified the following independent prognostic variables: primary tumor differentiation grade [4, 5, 11, 21–23, 25, 28, 29, 48], number of metastatic sites [2, 12, 14, 18, 21, 22, 25, 47, 66], primary tumor location [4, 6, 12, 22, 23, 25, 28, 66], extent of metastatic liver involvement [32, 48, 49, 75, 81, 89, 94], administration of chemotherapy [4, 14, 20, 24, 32, 39, 48, 49, 93], administration of anti‐VEGF therapy [2, 13, 21, 23], CEA levels [5, 12–14, 28, 32], age [4, 6, 18, 22, 25, 28, 29], Eastern Cooperative Oncology Group performance status (ECOG‐PS) [4, 14, …”

“…For patients with incurable colorectal cancer, an important question which remains unanswered to date is whether the best treatment strategy is primary tumor resection (PTR) with chemotherapy or immediate chemotherapy without PTR. Previous published comparative studies reported conflicting results on this issue, with some studies demonstrating improved survival with PTR compared to primary tumor intact (PTI) [2, 4–32], while other studies found no significant differences between the two groups [33–40], and other studies suggested systemic chemotherapy without resection of the primary tumor is the treatment strategy of choice for patients with incurable colorectal cancer [41–50]. The purpose of the present study was to perform a systematic review of the literature and employ meta‐analytical techniques to compare survival and adverse events in patients undergoing PTR versus PTI, with or without chemotherapy, in order to determine whether PTR should be performed in patients with incurable localized or metastatic colorectal cancer.…”

Primary tumor sidedness is an independent prognostic marker for survival in metastatic colorectal cancer: Results from a large retrospective cohort with mutational analysis

“…29 However, other studies have demonstrated a survival benefit in primary tumor resection among patients with metastatic colorectal cancer. [30][31][32] Current randomized studies are investigating the utility of upfront primary surgical resection (CAIRO4, 33 SYNCHRONOUS, 34 Korean NCT01978249 35 ), the results of which are greatly anticipated to further elucidate this question.…”

Antitumour metastasis and the antiangiogenic and antitumour effects of a Eimeria stiedae soluble protein

“…Surgery is the cornerstone treatment that relieves symptoms associated with obstruction, perforation or bleeding in patients with colorectal cancer who have an obstructed bowel. In patients with unresectable metastases and intact primary tumours that do not obstruct the bowel, systemic chemotherapy is the treatment of choice 2 . However, a large percentage of cancer patients eventually relapse and develop drug resistance 3,4 .…”