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Patients with stage IV colorectal cancer (CRC) who have not undergone primary tumor resection (PTR) are at risk of sudden medical emergencies. Despite the ongoing controversy over the necessity and timing of PTR in patients with stage IV CRC, studies comparing the survival outcomes of elective and emergency surgery in this population are scarce. This is a retrospective study conducted at a single institute. The patients were divided into two groups: the elective surgery (ELS) group (n = 46) and the emergency surgery (EMS) group (n = 26). The primary outcome was 2-year overall survival (OS). During a median follow-up period of 27.0 months, the 2-year OS was significantly better in the ELS group (80% vs. 42.9%, p = 0.002). No significant differences were observed in the 2-year relapse-free survival and 30-day postoperative complication rates. Planning and performing elective surgery could help increase the survival rate of patients with synchronous stage IV CRC, especially those that undergo simultaneous or staged metastasectomy.

BACKGROUND Patients with right sided colorectal cancer are known to have a poorer prognosis than patients with left sided colorectal cancer, whatever the cancer stage. To this day, primary tumor resection (PTR) is still controversial in a metastatic, non resectable setting. AIM To explore the survival impact of PTR in patients with metastatic colorectal cancer (mCRC) depending on PTL. METHODS We retrospectively collected data from all consecutive patients treated for mCRC at the Centre Georges Francois Leclerc Hospital. Univariate and multivariate Cox proportional hazard regression models were used to assess the influence of PTR on survival. We then evaluated the association between PTL and overall survival among patients who previously underwent or did not undergo PTR. A propensity score was performed to match cohorts. RESULTS Four hundred and sixty-six patients were included. A total of 153 (32.8%) patients had unresected synchronous mCRC and 313 (67.2%) patients had resected synchronous mCRC. The number of patients with right colic cancer, left colic cancer and rectal cancer was respectively 174 (37.3%), 203 (43.6%) and 89 (19.1%). In the multivariate analysis only PTL, PTR, resection of hepatic and or pulmonary metastases and the use of oxaliplatin, EGFR inhibitors or bevacizumab throughout treatment were associated to higher overall survival rates. Survival evaluation depending on PTR and PTL found that PTR improved the prognosis of both left and right sided mCRC. Results were confirmed by using a weighted propensity score. CONCLUSION In mCRC, PTR seems to confer a higher survival rate to patients whatever the PTL.

Background Non‐small cell lung cancer (NSCLC) patients with ipsilateral pleural dissemination (M1a) are generally contraindicated for surgery. Recently, several studies have demonstrated that these patients might benefit from primary tumor resection (PTR). However, whether PTR is beneficial for driver oncogene‐positive patients treated with targeted therapy, remains unclear. Here, we investigated the effects of PTR on survival in the era of targeted therapy. Methods In total, 105 NSCLC patients with ipsilateral pleural dissemination were identified. The mode of systemic treatment was assessed in this study. Survival analysis was performed with the Kaplan‐Meier method and Cox proportional hazards regression. The overall survival (OS) of patients with or without PTR was compared between propensity score‐matched groups (caliper: 0.02). Results In the entire cohort, PTR was associated with improved OS in both unmatched (median survival time [MST]: 50.0 vs. 29.6 months, P = 0.019) and matched (MST: 50.0 vs. 34.4 months, P = 0.052) cohorts. Multivariate regression models showed that surgery was an independent favorable prognostic factor for OS. A total of 70 patients underwent genetic testing, and targeted therapies, such as EGFR‐TKIs or ALK‐TKIs, were used in the driver oncogene‐positive patients. Subgroup analysis showed that PTR did not improve OS in the targeted therapy group (MST: 57.1 months vs. 50.4 months, P = 0.840). However, surgery significantly prolonged survival in the nontargeted therapy group (MST: 39.8 vs. 14.2 months, P = 0.002). Conclusions The results of this study indicated that PTR could prolong OS in stage IV NSCLC patients with ipsilateral pleural dissemination, especially in patients who are not candidates for targeted therapy. Key points Non‐small cell lung cancer patients with ipsilateral pleural dissemination can benefit from primary tumor resection.Primary tumor resection could prolong overall survival (OS) in non‐small cell lung cancer patients with ipsilateral pleural dissemination who are not candidates for targeted therapy., Non‐small cell lung cancer patients with ipsilateral pleural dissemination can benefit from primary tumor resection, especially patients who are not candidates for targeted therapy.

BackgroundA survival benefit was observed in metastatic bladder cancer patients who underwent primary tumor resection, but it was still confusing which patients are suitable for the surgery. For this purpose, we developed a model to screen stage M1 patients who would benefit from primary tumor resection.MethodsPatients with metastatic bladder cancer were screened from the Surveillance, Epidemiology, and End Results database (2004–2016) and then were divided into surgery (partial or complete cystectomy) group and non-surgery group. To balance the characteristics between them, a 1:1 propensity score matching analysis was applied. A hypothesis was proposed that the received primary tumor resection group has a more optimistic prognosis than the other group. The multivariable Cox model was used to explore the independent factors of survival time in two groups (beneficial and non-beneficial groups). Logistic regression was used to build a nomogram based on the significant predictive factors. Finally, a variety of methods are used to evaluate our model.ResultsA total of 7,965 patients with metastatic bladder cancer were included. And 3,314 patients met filtering standards, of which 545 (16.4%) received partial or complete cystectomy. Plots of the Kaplan–Meier and subgroup analyses confirmed our hypothesis. After propensity score matching analysis, a survival benefit was still observed that the surgery group has a longer median overall survival time (11.0 vs. 6.0 months, p < 0.001). Among the surgery cohort, 303 (65.8%) patients lived longer than 6 months (beneficial group). Differentiated characteristics included age, gender, TNM stage, histologic type, differentiation grade, and therapy, which were integrated as predictors to build a nomogram. The nomogram showed good discrimination in both training and validation cohorts (area under the receiver operating characteristic curve (AUC): 0.806 and 0.742, respectively), and the calibration curves demonstrated good consistency. Decision curve analysis showed that the nomogram was clinically useful. Compared with TNM staging, our model shows a better predictive value in identifying optimal patients for primary tumor resection.ConclusionsA practical predictive model was created and verified, which might be used to identify the optimal candidates for the partial or complete cystectomy group of the primary tumor among metastatic bladder cancer.

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

Objectives: Location of the primary tumor has prognostic value and predicts the effect of certain therapeutics in synchronous metastatic colorectal cancer. We investigated whether the association between primary tumor resection (PTR) and overall survival (OS) also depends on tumor location. Methods: Data on synchronous metastatic colorectal cancer patients from the Netherlands Cancer Registry (n=16,106) and Surveillance, Epidemiology, and End Results (SEER) registry (n=19,584) were extracted. Cox models using time-varying covariates were implemented. Median OS for right-sided colon cancer (RCC), left-sided colon cancer, and rectal cancer was calculated using inverse probability weighting and a landmark point of 6 months after diagnosis as reference. Results: The association between PTR and OS was dependent on tumor location (P

Introduction: The goal of primary tumor resection with lymphadenectomy (PTR) in small intestine neuroendocrine neoplasms (SI-NENs) is to avoid local recurrence while sparing as much of the small bowel as possible, even in the case of extensive mesenteric fibrosis. The results of PTR with retrograde vessel-sparing lymphadenectomy (VS-LA) were compared to those of conventional lymphadenectomy (Con-LA). Methods: Prospectively collected clinical, surgical and pathological data of consecutive patients with SI-NENs who underwent small bowel resections were retrospectively analyzed regarding the resection technique performed. Results: In a 7-year period, 50 of 102 patients with SI-NENs had only small bowel resections; of those, 25 were VS-LA and 25 were Con-LA. Patients with VS-LA had tendentially more advanced diseases with slightly higher rates of abdominal pain, mesenteric shrinkage and more level III lymph node involvement compared to patients with Con-LA. VS-LA, however, resulted in shorter resected bowel segments (median 40 cm vs. 65 cm, p = 0.007) with similar rates of local R0 resections (72% vs. 84%) and resected lymph nodes (median 13 vs. 13). Postoperative clinically relevant complications occurred in 1 of 25 (4%) in the VS-LA and in 7 of 25 (28%) patients in the Con-LA group (p = 0.02). Three months after surgery, 1 of 25 (4%) patients of the VS-LA group and 10 of 25 (40%) patients in the Con-LA group (p = 0.002) complained about abdominal pain. One of eight patients in the VS-LA group and two of thirteen patients in the Con-LA group who had completely resected stage III disease complained about diarrhea (p = 0.31). Conclusion: VS-LA seems to be oncologically safe and should be considered in small bowel resections for SI-NENs.

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.

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.

Background 5–10% of patients are diagnosed with metastatic breast cancer (MBC) at the initial diagnosis. This study aimed to develop a nomogram to predict the overall survival (OS) of these patients. Methods de novo MBC patients diagnosed in 2010–2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. They were randomly divided into a training and a validation cohort with a ratio of 2:1. The best subsets of covariates were identified to develop a nomogram predicting OS based on the smallest Akaike Information Criterion (AIC) value in the multivariate Cox models. The discrimination and calibration of the nomogram were evaluated using the Concordance index, the area under the time-dependent receiver operating characteristic curve (AUC) and calibration curves. Results In this study, we included 7986 patients with de novo MBC. The median follow-up time was 36 months (range: 0–83 months). Five thousand three-hundred twenty four patients were allocated into the training cohort while 2662 were allocated into the validation cohort. In the training cohort, age at diagnosis, race, marital status, differentiation grade, subtype, T stage, bone metastasis, brain metastasis, liver metastasis, lung metastasis, surgery and chemotherapy were selected to create the nomogram estimating the 1-, 3- and 5- year OS based on the smallest AIC value in the multivariate Cox models. The nomogram achieved a Concordance index of 0.723 (95% CI, 0.713–0.733) in the training cohort and 0.719 (95% CI, 0.705–0.734) in the validation cohort. AUC values of the nomogram indicated good specificity and sensitivity in the training and validation cohort. Calibration curves showed a favorable consistency between the predicted and actual survival probabilities. Conclusion The developed nomogram reliably predicted OS in patients with de novo MBC and presented a favorable discrimination ability. While further validation is needed, this may be a useful tool in clinical practice.

Background: Surgery has been the primary treatment in patients with localized gastrointestinal stromal tumors (GISTs) for many decades, whereas it remains controversial regarding the efficacy of primary tumor resection for metastatic GISTs treated with chemotherapy, and likewise it is unclear who would benefit from the surgical resection.Methods: GISTs patients with distant metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of surgery on survival.Results: In total, of 455 patients with metastatic GISTs, 235 patients (51.6%) underwent primary tumor resection and 220 patients (48.4%) did not. Median survival of patients in resection group was 72 (95% CI: 62.90–81.10) months vs. 40 (95% CI: 29.53–50.47) months for those in non-resection group (p < 0.001). Similarly, surgery in conjunction with chemotherapy led to a favorable impact on survival than chemotherapy alone (OS: 72 vs. 40 months, p < 0.001; CSS: 74 vs. 44 months, p < 0.001). Multivariable analysis showed that both OS (HR: 0.581, 95% CI: 0.386–0.874, p = 0.009) and CSS (HR: 0.663, 95% CI: 0.439–0.912, p = 0.042] were dramatically improved in patients with surgical removal of primary site, as well as primary tumor size between 5 and 10 cm, while increasing age was predictive of poorer survival. Stratified analysis revealed that patients with tumor locations in the stomach demonstrated a prolonged survival after surgery, with no significant differential surgical effect between the stomach and small intestine.Conclusions: Our study preliminarily suggests that carefully selected patients with metastatic GISTs might prolong survival after treatment of surgery, especially those with a primary tumor between 5 and 10 cm and a tumor located in the stomach.

Background The majority of hepatocellular carcinoma patients (HCCs) with extrahepatic metastases die of progressive intrahepatic tumor. There have been little data on the role of primary tumor resection (PTR) for HCCs with extrahepatic metastases but with resectable primary tumors. Methods A retrospective study was conducted on HCCs with extrahepatic metastases with resectable primary tumors who either underwent or did not undergo PTR in the SEER registry between 2004 and 2013. The overall and cancer‐specific survivals (OS and CSS) were assessed by the log‐rank test and the Cox proportional hazard regression model. A propensity score matching was conducted to minimize biases. Validation was performed in another cohort from the Sun Yat‐sen Memorial Hospital (SYSMH). Results Of the 529 HCCs with extrahepatic metastases with resectable primary tumors included into this study, 230 patients underwent PTR and 299 did not. The percentages of patients who underwent PTR increased from 38.6% in 2004 to 70.3% in 2013. In the propensity score‐matched patients, PTR was associated with improved OS (HR 0.310, P

Jie Wang,1,* Xiaobo Bo,1,* Pinxiang Lu,2,* Tao Suo,1 Xiaoling Ni,1 Han Liu,1 Hongtao Pan,1 Sheng Shen,1 Min Li,1 Dexiang Zhang,2 Yueqi Wang,1 Houbao Liu1 1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; 2Department of General Surgery, Xuhui Central Hospital, Shanghai, China *These authors contributed equally to this work Objective: To evaluate the therapeutic value of primary tumor resection (PTR) in metastatic ampullary cancer at the initial presentation. Patients and methods: Patients with metastatic ampullary cancer were identified from Surveillance, Epidemiology and End Results database. Propensity score matching (PSM) was performed to balance the characteristics of our cohort. Kaplan–Meier analyses, log-rank tests and multivariate Cox regression models were employed to evaluate the therapeutic value of PTR. Results: A total of 346 patients with metastatic ampullary cancer were identified from 2004 to 2014 and 90 patients were screened by PSM. PTR was associated with favorable overall survival (OS) and cancer-specific survival (CSS) after PSM (PTR vs no-PTR: 16.0, 95% CI: 9.0–22.0 vs 8.0, 95% CI: 5.0–11.0 for median OS; 22.0, 95% CI: 13.0–33.0 vs 9.0, 95% CI: 5.0–11.0 for median CSS; both log-rank P

Primary tumor resection (PTR) in advanced asymptomatic colorectal cancer (CRC) has been a matter of intense debate for long time. With the advances in systemic treatments, this practice has decreased over the years, although it remains still pervasive. Although the removal of primary tumor has been extensively interrogated both in retrospective and prospective studies, it still remains a clinical conundrum. There are many arguments for and against PTR in CRC both from the preclinical and the clinical point of view. Two scoring models have been published aiming at identifying patients who are suitable candidate for PTR, but they deserve further investigations in larger datasets. While awaiting the results of ongoing randomized clinical trials (RCTs) on this controversial topic, both upfront systemic treatment and PTR followed by chemotherapy should be considered valid options in patients with asymptomatic mCRC. Clinical selection and a shared-decision making approach are the keys to success.

The true survival benefit of different curative strategies involving type of operative procedure and timing for patients with initial noncurative colorectal liver metastases remains uncertain. The goal of this study was to examine the effect of primary tumor resection on patients’ survival and to clarify the predictive factors related to overall survival (OS). This was a retrospective study that included 219 patients with initial noncurative colorectal liver metastases without extrahepatic disease. The clinicopathological characteristics of patients and their survival were examined. Survival analysis was performed using the Kaplan–Meier method. All variables associated with P

// Jingfei Guo 1, 2, * , Qian Zhang 3, * , Xinyu Bi 1 , Jianguo Zhou 1 , Zhiyu Li 1 , Zhen Huang 1 , Yefan Zhang 1 , Muxing Li 1 , Xiao Chen 1 , Xuhui Hu 1 , Chi Yihebali 4 , Junbo Liang 5 , Jianmei Liu 6 , Jianjun Zhao 1 , Jianqiang Cai 1 , Hong Zhao 1 1 Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China 2 Academy of Medical Sciences, Peking Union Medical College, Beijing, China 3 Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 4 Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China 5 State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China 6 Laboratory of Cell and Molecular Biology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China * These authors have contributed equally to this work Correspondence to: Hong Zhao, email: zhaohong@cicams.ac.cn Jianqiang Cai, email: caijianqiang@cicams.ac.cn Jianjun Zhao, email: zjj8424@sina.com Keywords: midgut neuroendocrine tumor, liver metastasis, palliative surgery, primary tumor resection, survival benefit Received: August 15, 2016 Accepted: November 07, 2016 Published: December 24, 2016 ABSTRACT Background: Treatment for midgut neuroendocrine tumor patients with unresectable liver metastasis has long been a controversial issue. This system review aims to summarize existing evidence concerning the value of primary tumor resection in this group of patients. Results: 8 cohort studies were identified for qualitative analysis. None of them strictly met with the inclusion criteria and meta-analysis was impossible. There was a tendency towards better overall survival for the primary tumor resected group in all 8 studies, in which 6 demonstrated significant difference. Progression free survival to liver disease was prolonged and less patients died of liver failure in the resected group. Methods: MEDLINE, EMBASE and CENTRAL were searched until 2016/7/4 for relevant studies, with primary outcome being overall survival, and secondary outcome being progression free survival, cause of death and symptom relief. Conclusions: Current evidence supports resection of primary tumor for midgut neuroendocrine tumor patients with liver metastases, but randomized controlled trials are required to reach a final conclusion.

Background A majority of patients with rectal cancer and metastasis are not eligible to curative treatment because of an extensive and unresectable metastatic disease. Primary tumor resection is still debated in this situation. Rectal surgery treats or prevents the symptoms and avoids the risk of acute complications related to the primary tumor. Several studies on colorectal cancers seem to show interesting results in terms of survival in favor to the resection of the primary tumor. To date, no randomized trial or even a prospective study has assessed the impact of primary tumor resection on overall survival in patients with colorectal cancer with unresectable metastasis. All published studies were retrospective and included colon and rectal cancers. Rectal cancer is associated with specific problems related to the rectal surgery. Surgery is more complex, and may be source of more morbidity and postoperative functional dysfunctions (stoma, digestive, sexual, urinary) than colic surgery. On the other hand, symptoms related to the progression of rectal tumor are often very disabling: pain, rectal syndrome. Methods/Design GRECCAR 8 is a multicentre randomized open-label controlled trial aimed to evaluate the impact on survival of the primary tumor resection in rectal cancer with unresectable synchronous metastasis. Patients must undergo upfront systemic chemotherapy for at least 4 courses before inclusion. Patients with progressive metastatic disease during upfront chemotherapy will be excluded from the study. Patients will be randomly assigned in a 1:1 ratio to Arm A: primary tumor resection followed by systemic chemotherapy versus Arm B: systemic chemotherapy alone. Primary endpoint will be overall survival measured from the date of randomization to the date of death or to the end of follow-up (2 years). Secondary endpoints will include progression-free survival, quality of life, toxicity of chemotherapy, response of the primary tumor and metastatic disease to chemotherapy, postoperative morbidity and mortality, rate of patient not eligible for postoperative chemotherapy (arm A), primary tumor related complications and rate of emergency surgery (arm B). The number of patients needed is 290. Trial registration ClinicalTrial.gov: NCT02314182