Role Of Primary Tumor Resection Research Articles

The Real-Life Impact of Primary Tumor Resection of Synchronous Metastatic Colorectal Cancer-From a Clinical Oncologic Point of View.

The complex medical care of synchronous metastatic colorectal (smCRC) patients requires prudent multidisciplinary planning and treatments due to various challenges caused by the primary tumor and its metastases. The role of primary tumor resection (PTR) is currently uncertain; strong arguments exist for and against it. We aimed to define its effect and find its best place in our therapeutic methodology. We performed retrospective data analysis to investigate the clinical course of 449 smCRC patients, considering treatment modalities and the location of the primary tumor and comparing the clinical results of the patients with or without PTR between 1 January 2013 and 31 December 2018 at the Institute of Oncotherapy of the University of Pécs. A total of 63.5% of the 449 smCRC patients had PTR. Comparing their data to those whose primary tumor remained intact (IPT), we observed significant differences in median progression-free survival with first-line chemotherapy (mPFS1) (301 vs. 259 days; p < 0.0001; 1 y PFS 39.2% vs. 26.6%; OR 0.56 (95% CI 0.36-0.87)) and median overall survival (mOS) (760 vs. 495 days; p < 0.0001; 2 y OS 52.4 vs. 26.9%; OR 0.33 (95% CI 0.33-0.53)), respectively. However, in the PTR group, the average ECOG performance status was significantly better (0.98 vs. 1.1; p = 0.0456), and the use of molecularly targeted agents (MTA) (45.3 vs. 28.7%; p = 0.0005) and rate of metastasis ablation (MA) (21.8 vs. 1.2%; p < 0.0001) were also higher, which might explain the difference partially. Excluding the patients receiving MTA and MA from the comparison, the effect of PTR remained evident, as the mOS differences in the reduced PTR subgroup compared to the reduced IPT subgroup were still strongly significant (675 vs. 459 days; p = 0.0009; 2 y OS 45.9 vs. 24.1%; OR 0.37 (95% CI 0.18-0.79). Further subgroup analysis revealed that the site of the primary tumor also had a major impact on the outcome considering only the IPT patients; shorter mOS was observed in the extrapelvic IPT subgroup in contrast with the intrapelvic IPT group (422 vs. 584 days; p = 0.0026; 2 y OS 18.2 vs. 35.9%; OR 0.39 (95% CI 0.18-0.89)). Finally, as a remarkable finding, it should be emphasized that there were no differences in OS between the smCRC PTR subgroup and metachronous mCRC patients (mOS 760 vs. 710 days, p = 0.7504, 2 y OS OR 0.85 (95% CI 0.58-1.26)). The role of PTR in smCRC is still not professionally justified. Our survey found that most patients had benefited from PTR. Nevertheless, further prospective trials are needed to clarify the optimal treatment sequence of smCRC patients and understand this cancer disease's inherent biology.

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

BackgroundGastrointestinal 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).MethodsThe 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).ResultsAfter 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.ConclusionThe employment of PTR in patients with GI-NENLM is significantly correlated with individual survival benefits. We support performing PTR on carefully evaluated patients.

Does primary tumor resection improve survival for patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at diagnosis ?

Recent studies demonstrated that primary tumor resection (PTR) improves survival of patients with metastatic bone sarcomas. However, it remains quite unclear regarding the role of PTR in the treatment of sarcomas of pelvic bones with synchronous metastasis at diagnosis. Using the Surveillance, Epidemiology, and End Results Program, we enrolled a total of 385 patients with sarcomas of pelvic bones, sacrum, and coccyx who have metastasis at initial diagnosis, including 139 patients with osteosarcoma, 176 with Ewing sarcoma, and 70 with chondrosarcoma. Association between PTR and disease-specific survival (DSS) were investigated using the univariable and multivariable Cox regression models. Hazard ratio (HR) and 95% confidence interval (CI) were reported. Representative institutional PTR strategies and clinical outcomes for patients with metastatic pelvic sarcomas from our cancer center were displayed. The usage rate of PTR was 28.1% (39/139) in osteosarcoma, 13.6% (24/176) in Ewing sarcoma, and 41.4% (29/70) in chondrosarcoma with synchronous metastatic lesions. PTR was not associated with an improved DSS for metastatic pelvic osteosarcoma (HR = 0.686, 95% CI = 0.430 ~ 1.094, P = 0.113) and Ewing sarcoma (HR = 0.580, 95% CI = 0.291 ~ 1.154, P = 0.121). The use of PTR was associated with an improved DSS for metastatic pelvic chondrosarcoma (HR = 0.464, 95% CI = 0.225 ~ 0.954, P = 0.037). Primary lesion resection may provide a survival benefit for metastatic chondrosarcoma, but not for osteosarcoma and Ewing sarcoma of pelvic bones, sacrum, and coccyx. This population-based study recommends an active surgical intervention for metastatic chondrosarcoma while non-surgical treatment for metastatic osteosarcoma and Ewing sarcoma of the pelvis in terms of survival improvement.

Analysis of survival benefit from primary tumor resection and individualized prediction of overall survival for lung cancer patients with bone metastasis: Worth it or not?

BackgroundThe clinical management of lung cancer (LC) patients with bone metastasis (BM) is still a significant challenge. This study aimed to explore the role of primary tumor resection (PTR) on survival outcome of LC patients with BM and to develop two web-based nomograms for predicting the overall survival (OS) of LC patients with BM who received PTR and those who did not. MethodsWe enrolled LC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Propensity score matching (PSM) was then conducted to balance the baseline characteristics of covariates between patients in surgery and non-surgery groups. Next, Kaplan–Meier analysis with log-rank test was performed to evaluate the survival benefit of PTR before and after PSM methods and to explore the impact of surgical resection extent on the prognosis of LC patients with BM and clinical outcomes in patients with different metastatic patterns. Cox proportional hazard regression analysis was then applied to determine the independent prognostic factors for OS of patients receiving PTR and did not receiving PTR, respectively. Subsequently, we constructed two individualized nomograms for predicting the 12-, 18- and 24-months OS. Finally, receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were generated to evaluate discrimination, accuracy and clinical utility of the nomograms. ResultsA total of 7747 eligible patients were included in this analysis. The survival analysis revealed that PTR was closely associated with better survival outcome among LC patients with BM(P < 0.05), while the survival benefit of PTR was suboptimal in patients presented with multiple metastases(P > 0.05). Besides, lobectomy shows best survival benefit. Two nomograms were then constructed based on independent prognostic factors of patients in the surgery group and the non-surgery group. The ROC curves showed good discrimination of the two nomograms, with the area under curve (AUC) of each time point being higher than 0.7 in both the training set and testing set. The calibration curves also demonstrated satisfactory consistency between actual survival and nomogram-predicted OS of both nomograms. The DCA showed high benefit of nomogram in a clinical context. Moreover, the study population was stratified into three groups based on the scores of the nomogram, and the survival analysis showed that this prognostic stratification was statistically significant (p < 0.05). ConclusionsThis study showed that surgical resection of the primary site strategy can prolong survival of LC patients with BM to some extent, depending on different sites of metastasis and highly selected patients. Furthermore, the web-based nomograms showed significant accuracy in predicting OS for patients with or without surgery, which may provide valuable insights for patients’ counseling and individualized decision-making for clinicians.

Outcomes after primary tumor resection of metastatic pancreatic neuroendocrine tumors: An analysis of the National Cancer Database.

There is no consensus regarding the role of primary tumor resection for patients with metastatic pancreatic neuroendocrine tumors (panNET). We assessed surgical treatment patterns and evaluated the survival impact of primary tumor resection in patients with metastatic panNET. Patients with synchronous metastatic nonfunctional panNET in the National Cancer Database (2004-2016) were categorized based on whether they underwent primary tumor resection. We used logistic regressions to assess associations with primary tumor resection. We performed survival analyses with Kaplan-Meier survival functions, log-rank test, and Cox proportional hazard regression within a propensity score matched cohort. In the overall cohort of 2613 patients, 68% (n = 839) underwent primary tumor resection. The proportion of patients who underwent primary tumor resection decreased over time from 36% (2004) to 16% (2016, p < 0.001). After propensity score matching on age at diagnosis, median income quartile, tumor grade, size, liver metastasis, and hospital type, primary tumor resection was associated with longer median overall survival(OS) (65 vs. 24 months; p < 0.001) and was associated with lower hazard of mortality (HR: 0.39, p < 0.001). Primary tumor resection was significantly associated with improved OS, suggesting that, if feasible, surgical resection can be considered for well-selected patients with panNET and synchronous metastasis.

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

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. 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. 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). 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.

The role of primary tumor resection in synchronous stage IV colorectal cancer: Subgroup analysis.

47 Background: The standard treatment for synchronous stage IV colorectal cancer (CRC) is systemic chemotherapy. There have been attempts to conduct elective primary tumor resection (PTR) as an upfront treatment to prevent complications in primary tumor sites, or improve prognosis. However, there are controversies about the role of PTR in stage IV CRC. We investigated the prognostic role of PTR and tried to find subgroups who might get benefit from upfront PTR in this population. Methods: Between 2010 and 2020, 330 patients diagnosed with synchronous stage IV CRC at St. Vincent Hospital in Korea were retrospectively reviewed. We excluded patients underwent PTR and metastasectomy at the same time, PTR for emergencies (perforation, acute bleeding with hemodynamic instability, fistula, and/or obstruction), or received chemoradiotherapy as an initial treatment. Overall survival (OS) was measured from the date of diagnosis until death resulting from any cause or the last censored date during follow-up. OS were calculated using the Kaplan-Meier method, and differences in survival between groups were compared by the log-rank test. Variables with p value &lt;0.05 were included in the Cox regression multivariable model. Results: Total 223 patients were analyzed. Patients were divided into two groups; 45 patients receiving upfront elective PTR (PTR group), and the 178 patients receiving upfront systemic treatment (non-PTR group). Two groups were not different in terms of age ( p = 0.979), ECOG performance status ( p = 0.488), and serum CEA levels ( p = 0.252). However, the PTR group showed lesser number of metastatic organ compared to the non-PTR groups ( p = 0007). The PTR group survived longer than the non-PTR group ( p = 0.015). Multivariate analysis revealed that age≥60 (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.15-2.09; p = 0.004,), CEA≥30 ng/mL (HR, 1.32; 95% CI, 0.99-1.75, p = 0.061), PTR (HR, 0.66; 95% CI, 0.45-0.95; p =0.027), adding targeted agent (HR, 0.71; 95% CI, 0.53-0.96; p = 0.026), and ECOG≥3 (HR, 1.649; 95% CI, 1.15-2.37, p = 0.007) were associated with OS. Subgroup analysis showed that PTR might be beneficial in patients with low CEA (&lt;30 ng/mL, p = 0.032), old age (≥60, p = 0.028), ECOG (≤2, p = 0.006), M1a stage ( p = 0.008), and receiving bevacizumab ( p = 0.016). Conclusions: Upfront PTR was conducted in selected patients with lower number of metastasis, but associated with OS after adjusting other prognostic factors. We suggested that PTR could be an option for patients with low CEA (&lt;30 ng/mL), old age (≥60), ECOG (≤2), M1a stage, or receiving bevacizumab in this population.

413P Primary tumor resection (PTR) in metastatic colorectal cancer (mCRC) patients (pts) treated with upfront chemotherapy (CT) + bevacizumab (BEV): A pooled analysis of TRIBE and TRIBE2 studies

In mCRC treatment, the management of primary tumor still represents a complex and challenging issue for oncologists, especially in case of asymptomatic pts and during therapy with antiangiogenic drugs. The aim of the present analysis was to focus on the role of PTR in a pooled analysis of two randomized phase III studies (TRIBE and TRIBE2). This pooled-analysis included pts enrolled in the phase III TRIBE (NCT00719797) and TRIBE-2 (NCT02339116) studies that compared upfront FOLFOXIRI + BEV to FOLFIRI or FOLFOX + BEV, respectively. Association between PTR and adverse events experienced during 1st-line therapy was analyzed by χ2 test or Fisher’s exact test, as statistically appropriate. Survival curves were estimated with Kaplan-Meier method and compared by log-rank test. In our analysis, 1175 pts were included. Of them, 680 (58%) underwent PTR at baseline. Pts with resected primary tumor had more often a metachronous disease (p <0.001), a right sided colon cancer (p = 0.001), an ECOG PS 0 (p = 0.025), and a liver only metastatic disease (p = 0.006); moreover, they had more frequently received an adjuvant CT (p <0.001). Better progression-free survival (PFS) and overall survival (OS) were observed in pts who underwent PTR compared to those with unresected primary: 11.5 vs. 10.0 months (p <0.001) and 28.2 vs. 22.4 (p <0.001), respectively. In multivariate analysis, PTR was confirmed as an independent prognostic factor for better PFS (p = 0.05) together with triplet CT + BEV (p <0.0001), ECOG PS 0 (p <0.0001), RAS/BRAF wild-type cancer (p = 0.01) and liver-only metastatic disease (p = 0.02). About adverse events during 1st-line CT + BEV, in the group of pts with resected vs unresected primary tumor, diarrhea was more often observed (p = 0.028), whereas anemia (p = 0.044), perforation (p = 0.008), and gastrointestinal and surgical serious adverse events (p <0.0001) were less frequent. No statistically significant differences were noted in incidence of bleeding (p = 0.427). PTR impacted positively on prognosis of mCRC pts, and it was associated with less incidence of serious gastrointestinal and surgical adverse events during upfront CT plus BEV.

Current treatment landscape for oligometastatic non-small cell lung cancer.

The management of patients with advanced non-small cell lung carcinoma (NSCLC) has undergone major changes in recent years. On the one hand, improved sensitivity of diagnostic tests, both radiological and endoscopic, has altered the way patients are staged. On the other hand, the arrival of new drugs with antitumoral activity, such as targeted therapies or immunotherapy, has changed the prognosis of patients, improving disease control and prolonging survival. Finally, the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body. All of these advances have impacted the treatment of patients with advanced lung cancer, especially in a subgroup of these patients in which all of these treatment modalities converge. This poses a challenge for physicians who must decide upon the best treatment strategy for each patient, without solid evidence for one optimal mode of treatment in this patient population. The aim of this article is to review, from a practical and multidisciplinary perspective, published evidence on the management of oligometastatic NSCLC patients. We evaluate the different alternatives for radical ablative treatments, the role of primary tumor resection or radiation, the impact of systemic treatments, and the therapeutic sequence. In short, the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.

The Role of Primary Tumor Resection in Patients With Pancreatic Neuroendocrine Tumors With Liver Metastases.

BackgroundLiver metastases (LMs) are common in advanced pancreatic neuroendocrine tumor (PNET) patients. Currently, the benefit of primary tumor resection (PTR) in the setting of PNET patients with liver metastases is still controversial in several guidelines.MethodsData were extracted from the Surveillance, Epidemiology and End Results (SEER) database to evaluate this issue. The main index of interest in our study was overall survival time.ResultsInformation on 536 PNET patients with liver metastases from the SEER database was identified. A total of 214 patients (PTR group) received primary tumor resection, and more than half of them (132 patients) had synchronous LM resection. The other 322 PNET patients (non-PTR group) with liver metastases did not receive primary tumor resection. A significant survival benefit was gained from PTR when compared with non-PTR patients, both in OS (72.93 ± 2.7 vs. 36.80 ± 2.22 months) and 3- or 5-year survival rates (75.1% vs. 28.9% and 67.9% vs. 22.3%, respectively). No difference was found between PTR alone and PTR with synchronous LM resection. From univariate and multivariate analyses, younger age (<65 years) and good or moderate tumor differentiation may be more important when considering primary tumor resection. However, we found that all grades of tumor differentiation could result in a better overall survival time after primary tumor resection.ConclusionOur study suggested that primary tumor resection in pancreatic neuroendocrine patients with liver metastases could result in a longer survival time. Primary tumor resection with synchronous liver metastasis resection was not related to a better survival benefit. This treatment strategy may routinely be taken into consideration in these patients.

Sixty-Day Mortality of Patients With Metastatic Colorectal Cancer Randomized to Systemic Treatment vs Primary Tumor Resection Followed by Systemic Treatment

The role of primary tumor resection (PTR) in synchronous patients with metastatic colorectal cancer (mCRC) who had unresectable metastases and few or absent symptoms of their primary tumor is unclear. Studying subgroups with low postoperative mortality may identify patients who potentially benefit from PTR. To determine the difference in 60-day mortality between patients randomized to systemic treatment only vs PTR followed by systemic treatment, and to explore risk factors associated with 60-day mortality. CAIRO4 is a randomized phase 3 trial initiated in 2012 in which patients with mCRC were randomized to systemic treatment only or PTR followed by systemic treatment with palliative intent. This multicenter study was conducted by the Danish and Dutch Colorectal Cancer Group in general and academic hospitals in Denmark and the Netherlands. Patients included between August 2012 and December 2019 with histologically proven colorectal cancer, unresectable metastases, and a primary tumor with few or absent symptoms were eligible. Systemic treatment, consisting of fluoropyrimidine-based chemotherapy with bevacizumab vs PTR followed by fluoropyrimidine-based chemotherapy with bevacizumab. The aim of the current analysis was to compare 60-day mortality rates in both treatment arms. A secondary aim was the identification of risk factors for 60-day mortality in the treatment arms. These aims were not predefined in the study protocol. A total of 196 patients were included in the intention-to-treat analysis (112 [57%] men; median [IQR] age, 65 [59-70] years). Sixty-day mortality was 3% (95% CI, 1%-9%) in the systemic treatment arm and 11% (95% CI, 6%-19%) in the PTR arm (P = .03). In a per-protocol analysis, 60-day mortality was 2% (95% CI, 1%-7%) vs 10% (95% CI, 5%-18%; P = .048). Patients with elevated serum levels of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, and/or neutrophils who were randomized to PTR had a significantly higher 60-day mortality than patients without these characteristics. Patients with mCRC who were randomized to PTR followed by systemic treatment had a higher 60-day mortality than patients randomized to systemic treatment. Especially patients randomized to the PTR arm with elevated serum levels of lactate dehydrogenase, neutrophils, aspartate aminotransferase, and/or alanine aminotransferase were at high risk of postoperative mortality. Final study results on overall survival have to be awaited. ClinicalTrials.gov Identifier: NCT01606098.

Role of primary tumor resection in patients with metastatic medullary thyroid cancer who have unresectable distant metastases.

Whether patients with medullary thyroid carcinoma (MTC) who have unresectable synchronous distant metastases should undergo primary surgical resection (PTR) remains controversial. This study aimed to identify predictive factors associated with the survival of such patients. We conducted a retrospective study of patients with MTC who were registered in the Surveillance, Epidemiology, and End Results registry. The overall and cancer-specific mortality rates were assessed using risk-adjusted Cox proportional hazards regression modeling and stratified propensity score matching. One hundred and eight matched patients were assessed. Patients in the PTR group had lower overall mortality than did those in the non-PTR group. The 1-, 3-, and 5-year overall and cancer-specific survival rates in the PTR group were significantly higher. PTR appears to be the most appropriate intervention for patients with good performance status. Such patients are likely to benefit from surgery and to experience long-term stable disease.

Primary Tumor Resection Improves Survival for EGFR-TKI-Treated Patients With Occult M1a Lung Adenocarcinoma.

BackgroundThe role of primary tumor resection in occult M1a lung adenocarcinoma remains unclear, especially for patients receiving targeted therapy. The purpose of this study is to assess the effect of primary tumor resection on overall survival (OS) in lung adenocarcinoma patients with occult pleural disseminations receiving targeted therapy.MethodsLung adenocarcinoma patients with intraoperatively-confirmed occult pleural dissemination (M1a), who hospitalized in the Department of Thoracic Surgery in Fudan Shanghai Cancer Center from May 2008 to December 2017 and received EGFR-TKIs therapy, were enrolled. Log-rank tests were used to compare the survival differences between groups.Results34 patients receiving EGFR-TKIs were enrolled. The majority of them were never smokers (29/34, 85.3%). Among the enrolled patients, 20 (58.8%) patients underwent primary tumor resection, while 14 (41.2%) patients not. There was no distributional difference of baselines between patients undergoing and not undergoing primary tumor resection. Further analyses demonstrated that the patients undergoing primary tumor resection had a prolonged OS compared with those not (log-rank P= 0.042). The 2-year and 5-year OS for patients receiving primary tumor resection and EGFR-TKIs was 90.0% and 60.1%.ConclusionsPrimary tumor resection was associated with improved survival in patients with occult intraoperatively-confirmed M1a adenocarcinoma receiving EGFR-TKIs.

Resection of the primary gastrointestinal neuroendocrine tumor among patients with metastatic neuroendocrine tumors improves overall survival

Introduction: Among patients with metastatic gastrointestinal (GI) neuroendocrine tumor (NET), the role of primary tumor resection remains unknown. We sought to analyze if primary tumor resection of NET was associated improved overall survival (OS).

Resection of primary tumor in stage 4S neuroblastoma: a second study by the Italian Neuroblastoma Group.

To clarify the role of primary tumor resection in stage 4S neuroblastoma. We investigated a cohort of 172 infants diagnosed with stage 4S neuroblastoma between 1994 and 2013. Of 160 evaluable patients, 62 underwent upfront resection of the primary tumor and 98 did not. Five-year progression-free and overall survival were significantly better in those who had undergone upfront surgery (83.6% vs 64.2% and 96.8% vs 85.7%, respectively). One post-operative death and four non-fatal complications occurred in the resection group. Three patients who had not undergone resection died of chemotherapy-related toxicity. Thirteen patients underwent late surgery to remove a residual tumor, without complications: all but one alive. Outcomes were better in patients diagnosed from 2000 onwards. Infants diagnosed with stage 4S neuroblastoma who underwent upfront tumor resection had a better outcome. However, this result cannot be definitely attributed to surgery, since these patients were selected on the basis of their favorable presenting features. Although the question of whether to operate or not at disease onset is still unsolved, this study confirms the importance of obtaining enough adequate tumor tissue to enable histological and biological studies to properly address treatment, to achieve the best possible outcome.

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

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.

Role of Primary Tumor Resection for Metastatic Small Bowel Neuroendocrine Tumors.

While small bowel resection is well established as standard of care for curative-intent management of localized and loco-regional small bowel neuroendocrine tumors (SB-NETs), resection of the primary tumor in the setting of metastatic disease is debated. This review addresses the role of primary tumor resection for stage IV well-differentiated grade 1 and 2 SB-NETs. While survival benefits have been reported for primary tumor resection in the setting of metastatic disease, these studies are limited by selection bias and thus controversial. The main clinical benefits of primary tumor resection for stage IV disease involve the prevention of potentially debilitating complications associated with mesenteric fibrosis, including intestinal obstruction, mesenteric ischemia and angina, venous congestion, malabsorption, and malnutrition. Patients with metastases undergoing initial resection of the primary SB-NETs appear to have fewer episodes of care and re-intervention for loco-regional complications than those who do not undergo resection. As recommended by the NANETS and ENETS guidelines, resection of the primary tumor for stage IV SB-NETs should be strongly considered to avoid future loco-regional complications and potentially to improve survival. All patients with stage IV SB-NETs should be assessed by a surgeon experienced in the management of NETs to consider surgical therapies, including resection of the primary tumor despite metastatic disease.

Association of a Palliative Surgical Approach to Stage IV Pancreatic Neuroendocrine Neoplasms with Survival: A Systematic Review and Meta-Analysis.

The role of primary tumor resection in patients with pancreatic neuroendocrine neoplasms (PanNENs) and unresectable distant metastases remains controversial. We aimed to evaluate the effect of palliative primary tumor resection (PPTR) on overall survival (OS) in this setting. We searched the MEDLINE, Embase, Cochrane Library, Web of Science and SCOPUS databases up to January 2020 and used the Newcastle–Ottawa scale (NOS) criteria to assess quality/risk of bias. A total of 5661 articles were screened. In 10 studies, 5551 unique patients with stage IV PanNEN and unresectable metastases were included. The five-year OS for PanNEN patients undergoing PPTR in stage IV was 56.6% vs. 23.9% in the non-surgically treated patients (random effects relative risk (RR): 1.70; 95% CI: 1.53–1.89). Adjusted analysis of pooled hazard ratios (HR) confirmed longer OS in PanNEN patients undergoing PPTR (random effects HR: 2.67; 95% CI: 2.24–3.18). Cumulative OS analysis confirmed an attenuated survival benefit over time. The complication rate of PPTR was as high as 27%. In conclusion, PPTR may exert a survival benefit in stage IV PanNEN. However, the included studies were subject to selection bias, and special consideration should be given to PPTR anchored to a multimodal treatment strategy. Further longitudinal studies are warranted, with long-term follow-up addressing the survival outcomes associated with surgery in stage IV disease.

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

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

The Role of Primary Tumor Resection in Patients with Pleural Metastasis Encountered at the Time of Surgery.

BackgroundEvidence is lacking on whether the resection of lung parenchymal cancer improves the survival of patients with unexpected pleural metastasis encountered during surgery. We conducted a single-center retrospective study to determine the role of lung resection in the long-term survival of these patients.MethodsAmong 4683 patients who underwent lung surgery between 1995 and 2014, 132 (2.8%) had pleural metastasis. After excluding 2 patients who had incomplete medical records, 130 patients’ data were collected. Only a diagnostic pleural and/or lung biopsy was performed in 90 patients, while the lung parenchymal mass was resected in 40 patients.ResultsThe mean follow-up duration was 29.8 months. The 5-year survival rate of the resection group (34.7%±9.4%) was superior to that of the biopsy group (15.9%±4.3%, p=0.016). Multivariate Cox regression analysis demonstrated that primary tumor resection (p=0.041), systemic treatment (p<0.001), lower clinical N stage (p=0.018), and adenocarcinoma histology (p=0.009) were significant predictors of a favorable outcome. Interestingly, primary tumor resection only played a significant prognostic role in patients who received systemic treatment.ConclusionWhen pleural metastasis is unexpectedly encountered during surgical exploration, resection in conjunction with systemic treatment may improve long-term survival, especially in adenocarcinoma patients without lymph node metastasis.