Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

Identifying Optimal Candidates for Primary Tumor Resection Among Metastatic Pancreatic Cancer Patients: A Population-Based Predictive Model.

BACKGROUND: There is a controversy about whether surgery should proceed among metastatic pancreatic cancer (mPC) patients. A survival benefit was observed in mPC patients who underwent primary tumor resection; however, determining which patients would benefit from surgery is complex. For this purpose, we created a model to identify mPC patients who may benefit from primary tumor excision. METHODS: Patients with mPC were extracted from the Surveillance, Epidemiology, and End Results database, and separated into surgery and nonsurgery groups based on whether the primary tumor was resected. Propensity score matching (PSM) was applied to balance confounding factors between the two groups. A nomogram was developed using multivariable logistic regression to estimate surgical benefit. Our model is evaluated using multiple methods. RESULTS: About 662 of 14,183 mPC patients had primary tumor surgery. Kaplan-Meier analyses showed that the surgery group had a better prognosis. After PSM, a survival benefit was still observed in the surgery group. Among the surgery cohort, 202 patients survived longer than 4 months (surgery-beneficial group). The nomogram discriminated better in training and validation sets under the receiver operating characteristic (ROC) curve (AUC), and calibration curves were consistent. Decision curve analysis (DCA) revealed that it was clinically valuable. This model is better at identifying candidates for primary tumor excision. CONCLUSION: A helpful prediction model was developed and validated to identify ideal candidates who may benefit from primary tumor resection in mPC.

Impact on survival benefits of asymptomatic primary tumor resection after bevacizumab plus FOLFIRI as first-line therapy for patients with metastatic colorectal cancer with synchronous unresectable metastasis.

BACKGROUND: Metastatic colorectal cancer (mCRC) poses a clinical challenge and requires a combination of systemic therapy and conversion surgery. Although first-line chemotherapy and targeted therapy are considered the standard treatments for mCRC, the role of primary tumor resection (PTR) in asymptomatic synchronous mCRC with unresectable metastatic lesion after initial therapy remains relatively underexplored. MATERIALS: A retrospective review was conducted from January 2015 to January 2021, involving 74 patients with synchronous mCRC who received bevacizumab plus FOFIRI as first-line systemic therapy. All 74 patients had unresectable metastatic lesions confirmed through multidisciplinary team discussion. Patient characteristics, PTR data, and radiotherapy (RT) and overall survival (OS) outcomes were analyzed. The patients were categorized into a "PTR" group and a "No PTR" group and then further stratified into "4A," "4B," and "4C" subgroups based on the initial mCRC stage. Additionally, four subgroups-namely "PTR( +)/RT( +)," "PTR( +)/RT( -)," "PTR( -)/RT( +)," and "PTR( -)/RT( -)"-were formed to assess the combined effects of PTR and RT. RESULTS: The median OS for all the patients was 23.8 months (20.5-27.1 months). The "PTR" group exhibited a significantly higher median OS of 25.9 months (21.3-30.5 months) compared with 21.4 months (15.8-27.1 months) in the "No PTR" group (p = 0.048). Subgroup analyses revealed a trend of improved survival with PTR in patients with stage IVA and IVB; however, the results were not statistically significant (p = 0.116 and 0.493, respectively). A subgroup analysis of PTR and RT combinations revealed no significant difference in median OS rates. CONCLUSION: For asymptomatic mCRC with synchronous unresectable distant metastasis, PTR following first-line therapy with bevacizumab plus FOLFIRI may provide a potential survival benefit, particularly in stage IVA/IVB patients compared with stage IVC patients. Additionally, RT for primary tumor did not provide an additional OS benefit in mCRC with unresectable metastasis. A prospective randomized trial with a larger sample size is essential to further elucidate the role of PTR in this context.

Primary tumor resection for asymptomatic colorectal cancer patients with synchronous unresectable metastases: a meta-analysis of randomized controlled trials and case-matched studies.

PURPOSE: The value of upfront primary tumor resection (PTR) for asymptomatic unresectable metastatic colorectal cancer (mCRC) patients remains contentious. This meta-analysis aimed to assess the prognostic significance of upfront PTR for asymptomatic unresectable mCRC. METHODS: A systematic literature search was performed on June 21st, 2024. To minimize the bias and ensure robust evidence, only randomized controlled trials (RCTs) and case-matched studies (CMS) that compared PTR followed by chemotherapy to chemotherapy alone were included. The primary outcome was overall survival (OS), while cancer-specific survival (CSS) served as the secondary outcome. RESULTS: Eight studies (three RCTs and five CMS) involving 1221 patients were included. Compared to chemotherapy alone, upfront PTR followed by chemotherapy did not improve OS (hazard ratios [HR] 0.91, 95% confidence interval [CI] 0.79-1.04, P = 0.17), but was associated with slightly better CSS (HR 0.59, 95% CI 0.40-0.88, P = 0.009). CONCLUSIONS: The current limited evidence indicates that upfront PTR does not improve OS but may enhance CSS in asymptomatic unresectable mCRC patients. Ongoing trials are expected to provide more reliable evidence on this issue.

Influence of Primary Tumor Resection on Survival of Patients With Metastatic Siewert Type II Adenocarcinoma of the Esophagogastric Junction: A Population-Based, Propensity-Matched Analysis.

OBJECTIVE: It remains unclear whether primary tumor resection improves survival in patients with metastatic Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Therefore, our study attempted to investigate the prognostic value of primary tumor resection on metastatic AEG. METHODS: In total, 4200 patients diagnosed with metastatic AEG were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were categorized into two groups according to the performance of primary tumor resection. Pearson's chi-square test, Kaplan-Meier survival curve, and Cox regression analysis were conducted in this study. In addition, propensity-score matching was conducted to match 323 patients who received primary tumor resection and another 323 patients without. RESULTS: Multivariate Cox regression analysis demonstrated that primary tumor resection was a significant prognostic factor in patients with metastatic AEG before matching. Moreover, in the matched cohort, metastatic AEG patients receiving primary tumor resection had significantly longer overall survival (hazard ratio [HR]: .54, 95% confidence interval [CI]: .46-.64, P < .001) and cancer-specific survival (HR: .53, 95% CI: .45-.63, P < .001). Subgroup analysis similarly revealed that primary tumor resection was significantly associated with better survival in most subgroups. CONCLUSION: The present population-based study identified that primary tumor resection led to significantly superior survival in patients with metastatic AEG. These findings are likely to contribute to the development of individualized therapy in metastatic AEG.

Primary tumor resection improves survival of gastrointestinal neuroendocrine carcinoma patients with nonresected liver metastases.

BACKGROUND: The role of primary tumor resection (PTR) in the survival of gastrointestinal neuroendocrine carcinoma (GI-NEC) patients with liver metastases only remains poorly defined. Therefore, we investigated the impact of PTR on the survival of GI-NEC patients with nonresected liver metastases. METHODS: GI-NEC patients with a liver-confined metastatic disease diagnosed between 2016 and 2018 were identified in the National Cancer Database. Multiple imputations by chained equations were used to account for missing data, and the inverse probability of treatment weighting (IPTW) method was used to eliminate selection bias. Overall survival (OS) was compared by adjusted Kaplan-Meier curves and log-rank test with IPTW. RESULTS: A total of 767 GI-NEC patients with nonresected liver metastases were identified. Among all patients, 177 (23.1%) received PTR and had a significantly favorable OS before (median: 43.6 months [interquartile range, IQR, 10.3-64.4] vs. 8.8 months [IQR, 2.1-23.1], p < 0.001 in log-rank test) and after (median: 25.7 months [IQR, 10.0-64.4] vs. 9.3 months [IQR, 2.2-26.4], p < 0.001 in IPTW-adjusted log-rank test) the IPTW adjustment. Additionally, this survival advantage persisted in an adjusted Cox model (IPTW adjusted hazard ratio = 0.431, 95% confidence interval: 0.332-0.560; p < 0.001). The improved survival persisted in subgroups stratified by primary tumor site, tumor grade, and N stage, even in the complete cohort (excluding patients with missing data). CONCLUSIONS: PTR led to improved survival for GI-NEC patients with nonresected liver metastases regardless of primary tumor site, tumor grade, and N stage. However, the decision for PTR should be made on an individualized basis following multidisciplinary evaluation.

Resection of the primary tumor improves the prognosis of gastrointestinal neuroendocrine neoplasms with liver metastases: mutual validation based on SEER database and institutional data.

BACKGROUND: Gastrointestinal Neuroendocrine Neoplasms (GI-NENs) often result in liver metastases, and the role of Primary Tumor Resection (PTR) in managing GI-NENs with liver metastases (GI-NENLM) is still debated. This study aimed to investigate the potential benefits of PTR in treating GI-NENLM by analyzing data from the Surveillance, Epidemiology, and End Results Program (SEER) and the First Affiliated Hospital of Sun Yat-sen University (FAH). METHODS: The SEER Registry 17 database and the FAH clinical pathology database were used to collect clinicopathology data for GI-NENLM diagnosed between 2010 and 2019 and between 2011 and 2022, respectively. Propensity score matching (PSM) was used to match the clinicopathological characteristics of patients from both cohorts. Inverse probability weighting (IPTW) was used to weigh the PTR and non-PTR groups. The primary endpoint was overall survival (OS). RESULTS: After matching, 155 patients from the SEER database were matched to the FAH cohort. PTR was significantly associated with better prognosis in PSM-matched/unmatched SEER cohorts (P < 0.01) and in the FAH cohort even after eliminating selection bias using IPTW (p < 0.01). Subgroup analysis suggests that the cohort consisting of patients aged 55 years or older, individuals with colorectal primary tumors, those at the T1 disease stage, and those without extrahepatic metastasis may potentially benefit from PTR. Interaction analysis showed no significant interaction between PTR and other clinical and pathological factors except for age. CONCLUSION: The employment of PTR in patients with GI-NENLM is significantly correlated with individual survival benefits. We support performing PTR on carefully evaluated patients.

Surgical Management of the Primary Tumor in Stage IV Small Intestinal Neuroendocrine Tumors: To Operate or Not to Operate, That Is the Question.

PURPOSE OF REVIEW: Small intestinal neuroendocrine tumors (SI-NET) are rare tumors, often with distant metastases at diagnosis. The objective of this review is to provide an overview of the latest literature regarding surgical management of the primary tumor in stage IV SI-NET. RECENT FINDINGS: Primary tumor resection (PTR) seems to be associated with improved survival in patients with stage IV SI-NET, independent of treatment of distant metastases. A watch and wait approach of the primary tumor increases the risk of needing an emergency resection. PTR improves survival in patients with stage IV SI-NET, decreases the risk of emergency surgery, and should be considered in all patients with stage IV disease and unresectable liver metastasis.

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.

Development and validation of a nomogram to predict which patients with colorectal cancer liver metastases would benefit from primary tumor resection.

PURPOSE: The use of primary tumor resection (PTR) in the treatment of colorectal cancer liver metastases (CRLM) patients has become increasingly controversial. Our goal is to establish a nomogram to screen for the candidates that would benefit from PTR in CRLM patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was searched for 8366 patients with colorectal liver cancer metastases (CRLM) from 2010 to 2015. Overall survival (OS) rates were calculated using the Kaplan-Meier curve. After propensity score matching (PSM), predictors were analyzed by logistic regression analysis, and a nomogram was created to predict for survival benefit of PTR using R software. RESULTS: After PSM, there were 814 patients in both PTR group and non-PTR group, respectively. The median OS time in the PTR group was 26 months (95%CI = 23.33 ~ 28.67) and the median OS time in the non-PTR group was 15 months (95%CI = 13.36 ~ 16.64). The Cox regression analysis found that PTR was an independent predictive factor (HR = 0.46, 0.41 ~ 0.52) for OS. Additionally, logistic regression was used to study the factors impacting PTR benefit, and the results showed that CEA (P = 0.016), chemotherapy (P < 0.001), N stage (P < 0.001), histological grade (P < 0.001), and lung metastasis (P = 0.001) are independent predictive factors affecting the therapeutic outcome of PTR in patients with CRLM. The developed nomogram displayed good discriminative ability in predicting the beneficial probability of PTR surgery, with the area under the curve (AUC) values of 0.801 in training set and 0.739 in validation set respectively. CONCLUSION: We developed a nomogram that predicts the survival benefits of PTR in CRLM patients with relatively high accuracy, and quantifies the predictive factors for PTR-related benefits.

Colorectal cancer with synchronous unresectable liver metastases: resecting the primary tumor improves survival.

PURPOSE: The optimal treatment strategy of patients affected by colorectal cancer (CRC) with synchronous unresectable liver metastases (SULM) is at present undefined. It is not known if a palliative primary tumor resection followed by chemotherapy could have a survival benefit compared to upfront chemotherapy (CT). The aim of the study is to analyze the safety and effectiveness of both therapeutic strategies in a group of patients treated at one institution. METHODS: A prospectively collected database was queried for patients affected by colorectal cancer with synchronous unresectable liver metastases between January 2004 and December 2018, defining and comparing 2 groups: patients treated by chemotherapy alone (group 1) vs patients who underwent primary tumor resection with or without a first line chemotherapy (group 2). The primary end point was Overall Survival (OS), estimated by the Kaplan-Meier method. RESULTS: One hundred sixty-seven patients were included: 52 in group 1 and 115 in group 2, median follow-up 48 months (range 25-126). A difference of 14 months in overall survival was observed between group 2 compared to group 1 (28 vs 14 months respectively; p < 0.001). Furthermore, overall survival increased in patients who underwent liver metastases resection (p < 0.001) or percutaneous radiofrequency ablation after surgery (p < 0.001). CONCLUSION: With the limits of a retrospective analysis, the study shows that surgical resection of the primary tumor has a significant impact on survival compared to chemotherapy alone. Randomized controlled trials are needed to confirm these data.

Upfront primary tumor resection versus upfront systemic therapy for metastatic colorectal cancer: a systematic review and meta-analysis.

PURPOSE: The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC. METHODS: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies. RESULTS: After reviewing 3,626 articles, we identified 10 studies including a total of 48,696 patients. OS differed significantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57-0.68; p < 0.001). However, a subgroup analysis identified no significant difference in OS in RCTs (HR 0.97; 95% CI: 0.7-1.34; p = 0.83), whereas significant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54-0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed significantly between the treatment arms (risk ratio [RR] 3.52; 95% CI: 1.23-10.10; p = 0.02). CONCLUSIONS: In RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. However, upfront PTR seemed to increase OS in RCSs with PSM or IPTW. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required.

A population-based model identifying optimal candidate for primary tumor resection in distant metastatic laryngeal carcinoma.

PURPOSE: To developed a model to screen distant metastatic laryngeal carcinoma (DMLC) patients who would benefit from the primary tumor resection. METHODS: The propensity score matching (PSM) was utilized to avoid disproportionate distributions of the confounding factors. We hypothesized that patients who underwent surgery would benefit from surgery by having a longer median cancer-specific survival (CSS) than patients without surgery. Multivariable Cox model was used to explore the independent factors of CSS and overall survival (OS) among PSM population. We used these factors to construct a nomogram to identify surgery benefit patients. The predictive performance and clinical practicability of the nomogram were determined by area under the curve (AUC), calibration curve, and decision curve. RESULTS: The CSS and OS for patients who received primary tumor resection were significantly longer than those without resection (median CSS: 19 months vs. 10 months, P = 0.009; median OS: 21 months vs. 10 months, P = 0.001). The nomogram displayed a good degree of discrimination and calibration. The mean AUC of the nomogram was 0.70 (95% confidence interval [CI] 0.66-0.76) through threefold cross-validation. CONCLUSIONS: A predictive model was established and might be used to screen the optimal candidates for primary tumor surgery in DMLC patients.

Impact of primary tumor resection on the survival of patients with unresectable colon cancer liver metastasis at different colonic subsites: a propensity score matching analysis.

OBJECTIVE: To investigate the effect of primary tumor resection (PTR) on the prognosis of patients with unresectable colon cancer liver metastasis (UCCLM) at seven colonic subsites using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Propensity score matching (PSM) was performed to balance selection bias using all available variables that could be of potential relevance. After matching, the groups were redefined in a 1:1 ratio using the nearest method. Cancer-specific survival (CSS) was compared among the patients of PTR and non-PTR groups. Cox regression models were used to identify the prognostic factors for CSS. RESULTS: CSS was significantly different between all groups. Cox regression analysis showed that PTR was an independent prognostic factor for all groups. After PSM, PTR significantly prolonged CSS for all groups. Subgroup analysis showed that PTR did not improve the prognosis of N2 stage patients in the cecum, ascending colon, and descending colon groups; T1 + T2 stage patients in the hepatic flexure group; and patients with a tumor size ≤5 cm in the splenic flexure group. Segmental colectomy could prolong CSS of patients in the cecum, ascending colon, transverse colon, splenic flexure, and sigmoid colon groups, while extended colectomy could prolong CSS of patients in the hepatic flexure and descending colon groups. CONCLUSION: At different colonic subsites, UCCLM patients had different CSS. PTR could improve their prognosis, however, N stage, T stage, and tumor size are important reference indicators. In addition to patients in the hepatic flexure and descending colon groups, we suggested that patients in other groups should choose segmental colectomy.

Primary Tumor Resection Plus Chemotherapy versus Chemotherapy Alone for Colorectal Cancer Patients with Synchronous Bone Metastasis.

Background and Objective: Colorectal cancer (CRC) bone metastasis (BM), particularly synchronous metastasis, is infrequent and has a poor prognosis. Radical surgery for CRC with BM is challenging, and chemotherapy is the standard treatment. However, it is unclear whether combining chemotherapy with primary tumor resection (PTR) yields greater survival benefits than chemotherapy alone, as no relevant reports exist. Material and Methods: The Surveillance, Epidemiology, and End Results (SEER) database provided data on 1662 CRC patients with bone metastasis between 2010 and 2018, who were divided into two groups: chemotherapy combined with PTR and chemotherapy alone. Survival distributions were compared using the log-rank test, and survival estimates were obtained using the Kaplan-Meier method. A Cox proportional multivariate regression analysis was conducted to estimate the survival benefit of chemotherapy combined with PTR while controlling for additional prognostic factors. Results: The chemotherapy only group consisted of 1277 patients (76.8%), while the chemotherapy combined with PTR group contained 385 patients (23.2%). Patients who received chemotherapy combined with PTR had a significantly higher 1-year survival rate (60.7%) and 2-year survival rate (32.7%) compared to those who only received chemotherapy (43.8% and 18.4%, respectively; p < 0.0001). Independent prognostic factors identified by Cox proportional analysis were age, location of the primary tumor, type of tumor, M stage, metastasectomy and PTR. Patients who received chemotherapy combined with PTR had a significantly improved prognosis (HR 0.586, 95% CI 0.497-0.691, p < 0.0001). All subgroups demonstrated a survival advantage for patients who received chemotherapy in combination with PTR. Conclusions: Our findings suggest that patients with BM from CRC may benefit from chemotherapy combined with PTR. Our analysis also identified age, location of the primary tumor, type of tumor, M stage, metastasectomy, and PTR as independent prognostic risk factors for CRC patients with synchronous BM.

Small Intestinal Neuroendocrine Neoplasm: Factors Associated with the Development of Local Tumor-Related Symptoms.

INTRODUCTION: Clinical presentations of small intestinal neuroendocrine neoplasms (SiNENs) can range from asymptomatic to life-threatening complications. Other than primary tumor(s), mesenteric mass (MM) can provide local tumor-related (LTR) symptoms. Although some expert centers propose routine primary resection to avoid complications in stage IV patients, some guidelines suggest avoiding primary tumor resection unless in the presence of symptoms. This study was aimed to identify factors associated with the presence or development of LTR symptoms. METHODS: From 2012 to 2019, SiNEN patients with appropriate initial morphological imaging were included. All initial imaging was reviewed. Associations between factors and LTR symptoms were assessed by logistic regression. RESULTS: Among 144 SiNEN patients, 66 met the inclusion criteria. Multivariate analysis identified on initial morphological imaging (i) any visible primary tumor (p < 0.01) and (ii) MM contact ≥180° with the superior mesenteric vessels (p ≤ 0.02), as independent factors associated with LTR symptoms in the whole study population as well as in the subgroup of primary resected patients. Among the 14 (21%) patients with both factors on initial cross-sectional conventional imaging, 12 (18%) were straightaway symptomatic at diagnosis and the remaining became symptomatic during the follow-up. All asymptomatic patients, without upfront surgery and without any predictive factor 16/18 (89%), stayed asymptomatic during the 2.7-year median follow-up. The absence of association between these 2 factors yielded a sensitivity of 100%, a specificity of 62%, and a negative predictive value of 100% for the occurrence of LTR symptoms. CONCLUSION: The presence of any visible primary tumor and/or MM superior mesenteric vessels contact ≥180° at initial cross-sectional imaging are 2 easily identifiable factors, which can help physicians for the decision-making regarding timing and type of surgery for SiNENs. Larger multicenter studies should endorse these results.

Primary tumor resection with or without metastasectomy for left- and right-sided stage IV colorectal cancer: an instrumental variable analysis.

BACKGROUND: Whether primary tumor location (PTL) is predictive of survival benefits following primary tumor resection plus metastasectomy (PMTR) and primary tumor resection (PTR) alone in stage IV colorectal cancer patients is not known. We sought to address this issue by employing instrumental variable analysis to evaluate the efficacy of PMTR and PTR with stratification for primary tumor location in stage IV colorectal cancer patients. PATIENTS AND METHODS: Stage IV colorectal cancer patients diagnosed between January 1, 2005 and December 31, 2015 were identified from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. To account for both measured and unmeasured confounders, the efficacy of PMTR and PTR in the left- and right-sided subgroups was evaluated using instrumental variable analysis, with the health service area as the instrument variable. Overall survival (OS) was the primary outcome of interest. RESULTS: A total of 50,333 eligible patients were analyzed (left-sided, n = 29,402 and right-sided, n = 20,931). OS was significantly better with PMTR than with other treatments (PTR, metastasectomy only, or no surgery) in patients with left-sided tumors (hazard ratio [HR] = 0.37 [95% CI 0.24-0.58], P < 0.001), but not in patients with right-sided tumors (HR = 0.98 [95% CI 0.65-1.47], P = 0.910; interaction test P < 0.001). OS was comparable in patients treated with PTR and those treated with no surgery in both the left-sided (HR = 1.11 [95% CI 0.68-1.81], P = 0.690) and right-sided (HR = 0.85 [95% CI 0.50-1.43], P = 0.530; interaction test P = 0.466) subgroups. CONCLUSIONS: PMTR appears to only benefit patients with left-sided stage IV colorectal cancer but not those with right-sided tumors. PTR does not improve OS, regardless of primary tumor location. When selecting patients for PMTR, primary tumor location should be considered. Overuse of PTR should be avoided.

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

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.

Primary tumor resection improves prognosis of unresectable carcinomas of the transverse colon including flexures with liver metastasis: a preliminary population-based analysis.

PURPOSE: Studies on unresectable colorectal cancer liver metastasis(CRLM) rarely analyze the prognosis of the patients from the point of colonic subsites. We aimed to evaluate the effect of primary tumor resection (PTR) and different scope of colectomy on the prognosis of patients with unresectable transverse colon cancer liver metastasis (UTCLM), hepatic flexure cancer liver metastasis (UHFLM), and splenic flexure cancer liver metastasis (USFLM). PATIENTS AND METHODS: The patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cause-specific survival (CSS). Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of PTR on survival. RESULTS: In total, this study included a cohort of 1960 patients: 556 cases of UHFLM, 1008 cases of UTCLM, and 396 cases of USFLM. The median survival time of whole patients was 11.0 months, ranging from 7.0 months for UHFLM patients to 15.0 months for USFLM patients. USFLM patients had the best OS and CSS, followed by UTCLM patients. UHFLM patients had the worst OS and CSS (All P < 0.001). PTR could improve the OS and CSS of UTCLM, UHFLM, and USFLM (All P < 0.001). Subgroups analysis revealed that USFLM patients with tumor size≤5 cm and negative CEA had not demonstrated an improved OS and CSS after PTR. Multivariate analysis showed that PTR and perioperative chemotherapy were common independent prognostic factors for UHFLM, UTCLM, and USFLM patients. There was no difference between segmental colon resection and larger colon resection on CSS of UHFLM, UTCLM, and USFLM patients. CONCLUSIONS: We confirmed the different survival of patients with UTCLM, UHFLM, and USFLM, and for the first time, we proved that PTR could provide survival benefits for patients with unresectable CRLM from the perspective of colonic subsites of transverse colon, hepatic flexure, and splenic flexure. Besides, PTR may not improve the prognosis of USFLM patients with CEA- negative or tumor size≤5 cm. For oncologic outcomes, we concluded that segmental colon resection seemed an effective surgical procedure for UTCLM, UHFLM, and USFLM.

Debulking surgery for malignant tumors: the current status, evidence and future perspectives.

Debulking surgery, also called cytoreductive surgery, is a resection of the tumor as much as possible and an intended incomplete resection for unresectable malignant tumors. Since the most important principle in surgical oncology is complete R0 resection, debulking surgery goes against the basic principle and obscures the concept of operability. However, debulking surgery has been advocated for various types of advanced malignant tumors, including gynecological cancers, urological cancers, gastrointestinal cancers, breast cancers and other malignancies, with or without adjuvant therapy. Positive data from randomized trials have been shown in subsets of ovarian cancer, renal cell carcinoma, colorectal cancer and breast cancer. However, recent trials for renal cell carcinoma, colorectal cancer and breast cancer have tended to show controversial results, mainly according to the survival improvement of nonsurgical systemic therapy alone. On the other hand, debulking surgery still has a therapeutic role for slow-growing and borderline malignant tumors, such as pseudomyxoma peritonei and thymomas. The recent understanding of tumor heterogeneity and clonal evolution responsible for malignancy and drug resistance indicates that select patients may obtain prolonged survival by the synergistic effect of debulking surgery and novel systemic therapy. This review aimed to describe the current status and evidence of debulking surgery in a cross-organ manner and to discuss future perspectives in the current era with advances in systemic therapy.