Primary Tumor Resection for Rectal Cancer With Unresectable Liver Metastases: A Chance to Cut Is a Chance for Improved Survival

Background: About half of the patients with rectal cancer will develop liver metastasis during the course of their illness. Unfortunately, a large proportion of these metastases are unresectable. Surgical resection of the primary tumor vs. palliative treatment in patients with unresectable synchronous liver metastases remains controversial.Methods: Patients with rectal cancer with surgically unresectable liver metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. According to different treatment modalities, patients were divided into a primary tumor resection group and a non-resection group. Rates of primary tumor resection and survival were calculated for each year. Kaplan–Meier methods and Cox regression models were used to assess long-term survival. Multivariable logistic regression models were used to evaluate factors potentially associated with primary tumor resection.Results: Among 1,957 patients, 494 (25.2%) had undergone primary tumor resection. Patients with primary tumor resection had significantly better 5-year survival rate (27.2 vs. 5.6%, P < 0.001) compared to the non-resection group. Chemoradiotherapy with primary site resection was associated with the longest mean and 5-year OS (44.7 months, 32.4%). The Cox regression analyses of the subgroup indicated that patients who underwent primary tumor resection had improved survival compared with those who did not undergo resection in all 25 subgroups. Factors associated with primary tumor resection were well or moderately differentiated tumor grade, undergoing radiation, and primary tumor size <5 cm.Conclusions: The majority of patients with rectal cancer with unresectable liver metastases did not undergo primary tumor resection. Our results indicate that resection of the primary tumor appears to offer the greatest chance of survival. Prospective studies are needed to confirm these results.

Download Full-text

Subdivision of metastatic colorectal cancer for identifying patients who benefit more from primary tumor resection

10.21203/rs.3.rs-62901/v2 ◽

2021 ◽

Author(s):

Dakui Luo ◽

Zezhi Shan ◽

Zhiqiang Li ◽

Simin Chen ◽

Sanjun Cai ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Primary Tumor ◽

Cox Regression ◽

Tumor Resection ◽

Signet Ring Cell ◽

Normal Serum ◽

Primary Tumor Resection ◽

Cox Regression Analysis ◽

Serum Cea

Abstract Background Stage IV colorectal cancer (CRC) patients are heterogeneous with distinctive clinicopathologic features and prognosis. Radical resection of primary tumor and distant metastases is associated with improved survival outcomes in metastatic CRC. The value of palliative primary tumor resection is controversial. The present study explored which subgroups benefited more from primary tumor resection in metastatic CRC. Methods Between 2004 and 2015, patients with metastatic CRC were identified using the surveillance, epidemiology, and end results (SEER) database. Uni- and multivariable Cox regression analysis were performed to identify factors associated with decreased cancer-specific mortality. The subgroups were divided based on the independent prognostic factors. Results Age, marital status, race, serum CEA, histologic type, differentiation, tumor location, surgery of primary or metastatic lesion, site of metastases, number of metastatic sites, chemotherapy and radiotherapy were identified as independent prognostic factors. Patients with non-white race, normal serum CEA, non-signet ring cell carcinoma, well or moderate differentiation, surgery of metastases, isolated liver metastasis, single metastasis, receiving chemotherapy or radiotherapy presented more survival benefit from primary tumor resection. Conclusion Subgroup of metastatic CRC optimizes decision-making and selected patients will benefit more from primary tumor resection.

Download Full-text

Primary tumor resection in metastatic colorectal cancer (mCRC): A prospective cohort study.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.3584 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 3584-3584

Author(s):

Shu Fen Wong ◽

Kathryn M Field ◽

Suzanne Kosmider ◽

Jeanne Tie ◽

Hui-li Wong ◽

...

Keyword(s):

Primary Tumor ◽

Cox Regression ◽

Tumor Resection ◽

Tumor Burden ◽

Primary Tumor Resection ◽

Significant Survival ◽

The Impact ◽

Modern Era ◽

Systemic Therapies

3584 Background: The role of primary tumor resection in patients presenting with mCRC remains controversial. Previously reported survival benefits associated with primary tumor resection may not translate in the modern era of systemic therapies. We examined the impact of primary tumor resection on survival in a modern cohort of mCRC patients. Methods: Patients were identified using a clinician-designed mCRC registry involving 15 participating Australian sites from mid 2009. Patients were excluded if planned for curative metastasectomy or had incomplete data. Univariate logistic regression and multivariate cox regression was utilized to identify significant associations between resection, clinical variables and survival outcomes. Results: We identified 682 mCRC patients with median follow up 20 months. 40% (n = 275) had their primary in-situ. Rates of primary resection were higher for age > 70 years (OR 1.66 95% CI [1.22 – 2.26], p = 0.001) and Charlson score ≥3 (OR 1.50 [1.10 – 2.06], p = 0.011). Lower resection rates were observed for rectal v colon primary (OR 0.39 [0.28 – 0.55], p < 0.001), liver metastases (OR 0.59 [0.42 – 0.82], p = 0.002) and ECOG 2 - 4 (OR 0.64 [0.45 – 0.92], p = 0.015). There was a significant survival advantage for pts with primary tumor resection (median OS 21.3 vs 16.8 months; HR 0.63, p < 0.001), even when adjusting for known prognostic factors in a multivariate analysis (HR 0.56 [0.44 – 0.72], p < 0.001). Multivariate analyses also demonstrated that age > 70 years (HR 1.32 [1.03 – 1.71], p = 0.031) and ECOG ≥ 2 (HR 3.17 [2.43 – 4.15], p < 0.001) were significantly associated with poorer outcomes; whereas chemotherapy use (HR 0.61 [0.45 – 0.84], p = 0.002), bevacizumab use (HR 0.68 [0.52 – 0.89], p = 0.005) and rectal primary (HR 0.69 [0.53 – 0.91], p = 0.009) predicted improved survival. Conclusions: Our study suggests that primary tumor resection is associated with significant survival advantages for mCRC patients in the modern era of systemic therapies. The 40% of primary cancers in-situ is higher than previous mCRC studies and suggests a tendency for non-operative intervention in Australia. Further analysis aimed at examining the impact of other confounding variables such as tumor burden is ongoing and will be presented.

Download Full-text

Prognostic value of primary tumor resection in synchronous metastatic colorectal cancer (mCRC): Individual patient data (IPD) analysis of first-line randomized trials from the ARCAD database.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.658 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 658-658

Author(s):

Miriam Koopman ◽

Qian Shi ◽

Kaitlyn K.H. Goey ◽

Erin Green ◽

Volker Heinemann ◽

...

Keyword(s):

Primary Tumor ◽

Prognostic Value ◽

Randomized Trials ◽

Performance Status ◽

Tumor Resection ◽

Primary Tumor Resection ◽

Lung Involvement ◽

First Line ◽

Resection Group ◽

Anti Vegf

658 Background: In patients (pts) with mCRC with an asymptomatic primary tumor, there is limited evidence regarding the indication for primary tumor resection. The primary objective was to evaluate the prognostic value of primary tumor resection in synchronous mCRC pts. Methods: In this IPD analysis, a total of 3,423 pts from 8 first-line randomized trials (RCTs) with systemic therapy in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Five RCTs included targeted (anti-VEGF and/or anti-EGFR) agents. Synchronous mCRC was defined as distant metastases occurring ≤ 6 months of the initial CRC diagnosis. Overall survival (OS) and progression-free survival (PFS) were compared by stratified multivariate Cox models. Results: There were 710 (21%), 1,705 (50%) and 1,008 (29%) pts with non-resected and resected synchronous mCRC and metachronous mCRC, respectively. Compared to the non-resection group, pts in the synchronous resection group were associated with female gender, colon tumor, isolated liver/lung involvement, single metastatic site, and lower LDH (all p<.001). Adjusted for age, gender, performance status and prior chemotherapy, the non-resection group had a significantly worse median OS (16.4m) compared to the resection (22.2m; HR 1.60, 95% CI 1.43-1.78) and metachronous (22.4m; HR 1.81, 95% CI 1.58-2.07) groups. Similarly, PFS was significantly worse for the non-resection group (7.9m) compared to the resection (9.7m; HR 1.31, 95% CI 1.19-1.44) and metachronous group (8.9m; HR 1.47, 95% CI 1.30-1.66). Similar trends were observed in pts treated with non-targeted vs targeted agents, and anti-VEGF vs anti-EGFR therapy. In a subset analysis (n= 526), the observed associations remained after additional adjustment for primary tumor location, liver/lung involvement, number of metastatic sites, BMI and LDH. Conclusions: In this largest IPD analysis of mCRC trials to date, primary tumor resection is associated with better OS and PFS in synchronous mCRC pts. These results may be subject to bias since reasons for (non)resection were not available. Prospective RCTs on this topic are ongoing.

Download Full-text

Role of Up-Front Primary Tumor Resection and Tumor Sidedness in the Survival of Synchronous Metastatic Colon Cancer Patients

Digestive Surgery ◽

10.1159/000517477 ◽

2021 ◽

pp. 1-7

Author(s):

Dave E.W. van der Kruijssen ◽

Karlijn L. van Rooijen ◽

Sophie A. Kurk ◽

Johannes H.W. de Wilt ◽

Cornelis J.A. Punt ◽

...

Keyword(s):

Colon Cancer ◽

Confidence Interval ◽

Primary Tumor ◽

Cox Regression ◽

Performance Status ◽

Tumor Resection ◽

Serum Lactate ◽

Primary Tumor Resection ◽

Serum Lactate Dehydrogenase ◽

Metastatic Colon Cancer

Introduction: Uncertainty exists about a possible survival benefit of primary tumor resection (PTR) in synchronous metastatic colon cancer (mCC). Since sidedness of the primary tumor is regarded as an important prognostic factor, our objective was to study the interaction between PTR and sidedness in synchronous mCC. Methods: In this retrospective study, we used data from 2 first-line phase 3 randomized controlled trials (RCTs). A mixed Cox regression model was used to study the multiplicative interaction between PTR and sidedness. We adjusted for age, treatment arm, WHO performance status, number of affected organs by metastases, serum lactate dehydrogenase, and year of enrollment. Results: We found that PTR is associated with better survival in both right-sided (hazard ratio [HR] 0.59 [95% confidence interval 0.42–0.8 2]) and left-sided mCC (HR 0.70 [95% confidence interval 0.52–0.93]). The interaction between PTR and sidedness was not significant (p = 0.45). Conclusion: Our data suggest that the prognostic value of PTR is independent of sidedness. Validation of these results will be performed in ongoing RCTs.

Download Full-text

Subdivision of metastatic colorectal cancer for identifying patients who benefit more from primary tumor resection

10.21203/rs.3.rs-62901/v1 ◽

2020 ◽

Author(s):

Dakui Luo ◽

Zezhi Shan ◽

Qi Liu ◽

Sanjun Cai ◽

Qingguo Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Factors ◽

Primary Tumor ◽

Cox Regression ◽

Tumor Resection ◽

Signet Ring Cell ◽

Normal Serum ◽

Primary Tumor Resection ◽

Cox Regression Analysis ◽

Serum Cea

Download Full-text

The Impact of Primary Tumor Resection on Survival in Asymptomatic Colorectal Cancer Patients With Unresectable Metastases

Annals of Coloproctology ◽

10.3393/ac.2020.09.15.1 ◽

2021 ◽

Vol 37 (2) ◽

pp. 94-100

Author(s):

Ki Yoon Doah ◽

Ui Sup Shin ◽

Byong Ho Jeon ◽

Sang Sik Cho ◽

Sun Mi Moon

Keyword(s):

Colorectal Cancer ◽

Primary Tumor ◽

Cox Regression ◽

Tumor Resection ◽

Stage Iv ◽

Primary Tumor Resection ◽

Multivariate Logistic Regression Model ◽

Risk Of Cancer ◽

The Impact ◽

Unresectable Metastases

Purpose: This study was conducted to evaluate the effectiveness of primary tumor resection (PTR) in asymptomatic colorectal cancer (CRC) patients with unresectable metastases using the inverse probability of treatment weighting (IPTW) method to minimize selection bias.Methods: We selected 146 patients diagnosed with stage IV CRC with unresectable metastasis between 2001 and 2018 from our institutional database. In a multivariate logistic regression model using the patients’ baseline covariates associated with PTR, we applied the IPTW method based on a propensity score and performed a weighted Cox proportional regression analysis to estimate survival according to PTR.Results: Upfront PTR was performed in 98 patients, and no significant differences in baseline factors were detected. The upweighted median survival of the PTR group was 18 months and that of the non-PTR group was 15 months (P = 0.15). After applying the IPTW, the PTR was still insignificant in the univariate Cox regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.5–1.21). However, in the multivariate weighted Cox regression with adjustment for other covariates, the PTR showed a significantly decreased risk of cancer-related death (HR, 0.61; 95% CI, 0.40–0.94).Conclusion: In this study, we showed that asymptomatic CRC patients with unresectable metastases could gain a survival benefit from upfront PTR by analysis with the IPTW method. However, randomized controlled trials are mandatory.

Download Full-text

The prognostic impact of primary tumor resection in pancreatic neuroendocrine tumors with synchronous multifocal liver metastases

Pancreatology ◽

10.1016/j.pan.2018.04.014 ◽

2018 ◽

Vol 18 (5) ◽

pp. 608-614 ◽

Cited By ~ 5

Author(s):

Chen Lin ◽

Hongmei Dai ◽

Xiafei Hong ◽

Haiyu Pang ◽

Xianze Wang ◽

...

Keyword(s):

Liver Metastases ◽

Neuroendocrine Tumors ◽

Primary Tumor ◽

Tumor Resection ◽

Primary Tumor Resection ◽

Prognostic Impact ◽

Pancreatic Neuroendocrine Tumors

Download Full-text

Primary Tumor Resection Is Associated with a Better Outcome among Advanced EGFR-Mutant Lung Adenocarcinoma Patients Receiving EGFR-TKI Treatment

Oncology ◽

10.1159/000509664 ◽

2020 ◽

Vol 99 (1) ◽

pp. 32-40

Author(s):

Jeng-Sen Tseng ◽

Kuo-Hsuan Hsu ◽

Zhe-Rong Zheng ◽

Tsung-Ying Yang ◽

Kun-Chieh Chen ◽

...

Keyword(s):

Overall Survival ◽

Lung Adenocarcinoma ◽

Primary Tumor ◽

Tumor Resection ◽

Progression Free Survival ◽

Primary Tumor Resection ◽

Free Survival ◽

Resection Group ◽

Metastatic Burden ◽

Egfr Tki

Objectives: The characteristics and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in advanced EGFR-mutant lung adenocarcinoma patients with primary tumor resection (PTR) is not yet clear. Methods: We enrolled advanced EGFR-mutant lung adenocarcinoma patients with EGFR-TKI as first-line therapy to access the impact of PTR on the outcomes. Results: A total of 466 patients were enrolled with 76 patients (16.3%) undergoing PTR; 59 patients recurred after curative surgery, while 17 patients underwent surgery as diagnostic purposes. PTR patients displayed a better performance status, a lower metastatic burden, and much less measurable diseases (30.3 vs. 97.4%, p < 0.001). PTR patients experienced a significantly longer progression-free survival (25.1 [95% CI 16.6–33.7] vs. 9.4 [95% CI 8.4–10.4] months; aHR 0.40 [95% CI 0.30–0.54], p < 0.001) and overall survival (56.8 [95% CI 36.3–77.2] vs. 31.8 [95% CI 28.2–35.4] months; aHR 0.57 [95% CI 0.39–0.84], p = 0.004). Survival advantage was still observed while comparing PTR patients with the better performance and lower metastatic burden subgroup found within the non-resection group. Moreover, the progression-free survival and overall survival of 11 patients who were found having pleural metastases during surgery and underwent PTR plus pleural biopsy, were also longer than those with pure N0--1/M1a-malignant pleural effusion disease in the non-resection group (n = 19) (p < 0.001 and p = 0.002, respectively). Conclusion: PTR was associated with significantly better outcomes in advanced lung adenocarcinoma patients treated with EGFR-TKI. Further studies are needed to evaluate the biological role of PTR among these patients.

Download Full-text