OBJECTIVE: 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.

Patients who undergo primary tumor resection (PTR) reportedly have significantly higher overall survival (OS) than those who do not undergo this procedure. However, this result is only evident in past retrospective studies, and clinical trial results did not show the same trend. Thus, it remains unclear whether primary tumor resection effectively increases survival in patients with metastatic colorectal cancer (mCRC) across different study designs. We compared the OS of patients with asymptomatic unresectable mCRC who underwent PTR with that of those who did not. This retrospective cohort study was designed to be a target trial emulation of a randomized controlled trial (RCT) that would have compared the effectiveness of PTR versus non-PTR in patients with asymptomatic unresectable mCRC from 2009 to 2017. A systematic review and meta-analysis were conducted to compare the efficacy of PTR and non-PTR in patients with mCRC, and corresponding results were compared. This cohort included 1,132 patients for a per-protocol analysis. The PTR group had non-significantly longer survival (adjusted hazard ratio: 0.70, 95% confidence interval: 0.62-1.01) than the non-PTR group in our cohort. A meta-analysis including five RCTs (1,016 patients) and our cohort found that the PTR group did not have a significantly lower mortality rate than the non-PTR group. The results of this cohort study and previous RCTs suggest that PTR is not associated with improved survival compared to systemic chemotherapy combined with targeted therapy among asymptomatic unresectable mCRC patients. Therefore, routine PTR is not recommended in these patients.

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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)).
CONCLUSIONS: 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.

The implementation of primary tumor resection (PTR) in the treatment of kidney cancer patients (KC) with bone metastases (BM) has been controversial. This study aims to construct the first tool that can accurately predict the likelihood of PTR benefit in KC patients with BM (KCBM) and select the optimal surgical candidates. This study acquired data on all patients diagnosed with KCBM during 2010-2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was utilized to achieve balanced matching of PTR and non-PTR groups to eliminate selection bias and confounding factors. The median overall survival (OS) of the non-PTR group was used as the threshold to categorize the PTR group into PTR-beneficial and PTR-Nonbeneficial subgroups. Kaplan-Meier (K-M) survival analysis was used for comparison of survival differences and median OS between groups. Risk factors associated with PTR-beneficial were identified using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC), area under the curve (AUC), calibration curves, and decision curve analysis (DCA) were used to validate the predictive performance and clinical utility of the nomogram. Ultimately, 1963 KCBM patients meeting screening criteria were recruited. Of these, 962 patients received PTR and the remaining 1061 patients did not receive PTR. After 1:1 PSM, there were 308 patients in both PTR and non-PTR groups. The K-M survival analysis results showed noteworthy survival disparities between PTR and non-PTR groups, both before and after PSM (p < 0.001). In the logistic regression results of the PTR group, histological type, T/N stage and lung metastasis were shown to be independent risk factors associated with PTR-beneficial. The web-based nomogram allows clinicians to enter risk variables directly and quickly obtain PTR beneficial probabilities. The validation results showed the excellent predictive performance and clinical utility of the nomograms for accurate screening of optimal surgical candidates for KCBM. This study constructed an easy-to-use nomogram based on conventional clinicopathologic variables to accurately select the optimal surgical candidates for KCBM patients.

UNASSIGNED: Patients with advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LAD) inevitably experience drug resistance following treatment with EGFR-tyrosine kinase inhibitors (TKIs).
UNASSIGNED: We aimed to analyze the effect of primary tumor consolidative therapy (PTCT) on patients treated with first-line osimertinib.
UNASSIGNED: This retrospective cohort study was conducted in patients with advanced stage III or stage IV LAD with EGFR-sensitizing mutations (exon 19 deletion or L858R mutation) with disease control after first-line osimertinib. A curative dose of primary tumor radiotherapy or primary tumor resection was classified as PTCT. We compared the progression-free survival (PFS) and overall survival (OS) of patients with and without PTCT.
UNASSIGNED: This study included 106 patients with a median age of 61.0 years, and of those, 42% were male and 73.6% were never-smokers. Exon 19 deletion was observed in 67.9%, 30.2% had a programmed cell death ligand 1 (PD-L1) tumor proportion score <1%, 33.0% had brain metastasis, and 40.6% had oligometastasis. In all, 53 (50%) patients underwent PTCT. Patients who underwent PTCT demonstrated significantly better PFS [30.3 (95% confidence interval (CI), 24.1-36.4) versus 18.2 (95% CI, 16.1-20.2) months; p = 0.005] and OS [not reached versus 36.7 (95% CI, 32.5-40.9) months; p = 0.005] than patients who did not. A multivariate analysis showed that PTCT was an independent factor associated with better PFS [hazard ratio (HR), 0.22; 95% CI, 0.10-0.49; p < 0.001] and OS [HR, 0.10; 95% CI, 0.01-0.82; p = 0.032]. The PFS benefits of PTCT were consistent across subgroups, and the HR tended to be lower in patients aged <65 years, males, smokers, stage IVB disease, L858R, PD-L1 expression ⩾1%, non-oligometastasis, and brain metastasis.
UNASSIGNED: Of the patients with advanced EGFR-mutant LAD, those who underwent PTCT had a significantly better survival outcome than those who did not. The survival benefits were consistent across different subgroups.

BACKGROUND: The decision to resect or not the primary tumor in asymptomatic patients with synchronous metastatic colorectal cancer (mCRC) is a complex and challenging issue for oncologists, especially when an antiangiogenic-based therapy is planned.
METHODS: Patients enrolled in the phase III TRIBE and TRIBE2 studies that compared upfront FOLFOXIRI + bevacizumab to FOLFIRI or FOLFOX + bevacizumab, respectively, were included. We assessed the association of primary tumor resection (PTR) with progression-free survival (PFS), overall survival (OS), response rate (ORR), rate of grade > 2 adverse events (AEs), and serious gastrointestinal and surgical AEs in the overall population and according to the treatment arm.
RESULTS: Of the 999 patients included, 513 (51%) underwent PTR at baseline. Longer PFS and OS were observed in resected patients compared to those with unresected primary tumors: 11.2 vs. 10.0 months (p < 0.001) and 26.6 vs. 22.5 (p < 0.001), respectively. In multivariate models, PTR was confirmed as an independent prognostic factor for better PFS (p = 0.032) and OS (p = 0.018). Patients with PTR experienced a higher incidence of grade 3 or 4 diarrhea (p = 0.055) and lower incidence of anemia (p = 0.053), perforation (p = 0.015), and serious gastrointestinal and surgical AEs (p < 0.001). No statistically significant differences were noted in incidence of bleeding (p = 0.39). The benefit of FOLFOXIRI + bevacizumab in terms of PFS (p for interaction: 0.46), OS (p for interaction: 0.80), ORR (p for interaction: 0.36), and incidence of grade 3 or 4 AEs was independent of PTR.
CONCLUSIONS: PTR at baseline was independently associated with good prognosis in synchronous mCRC patients and with lower incidence of serious gastrointestinal and surgical AEs during upfront chemotherapy plus bevacizumab. The benefit and toxicity profile of FOLFOXIRI plus bevacizumab was independent of PTR.

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.
CONCLUSIONS: The employment of PTR in patients with GI-NENLM is significantly correlated with individual survival benefits. We support performing PTR on carefully evaluated patients.

The role of upfront primary tumor resection (PTR) in patients with unresectable metastatic colorectal cancer without severe symptoms remains controversial. We retrospectively analyzed the role of PTR in overall survival (OS) in this population. Among the 205 patients who enrolled, the PTR group (n = 42) showed better performance (p = 0.061), had higher frequencies of right-sided origin (p = 0.058), the T4 stage (p = 0.003), the M1a stage (p = 0.012), and <2 organ metastases (p = 0.002), and received fewer targeted agents (p = 0.011) than the chemotherapy group (n = 163). The PTR group showed a trend for longer OS (20.5 versus 16.0 months, p = 0.064) but was not related to OS in Cox regression multivariate analysis (p = 0.220). The male sex (p = 0.061), a good performance status (p = 0.078), the T3 stage (p = 0.060), the M1a stage (p = 0.042), <2 organ metastases (p = 0.035), an RAS wild tumor (p = 0.054), and the administration of targeted agents (p = 0.037), especially bevacizumab (p = 0.067), seemed to be related to PTR benefits. Upfront PTR could be considered beneficial in some subgroups, but these findings require larger studies to verify.

The impact of surgical resection of primary (PTR) on the survival of breast cancer (BC) patients with bone metastasis (BM) has been preliminarily investigated, but it remains unclear which patients are suitable for this procedure. Finally, this study aims to develop a predictive model to screen BC patients with BM who would benefit from local surgery.
BC patients with BM were identified using the Surveillance, Epidemiology, and End Results (SEER) database (2010 and 2015), and 39 patients were obtained for external validation from an Asian medical center. According to the status of local surgery, patients were divided into Surgery and Non-surgery groups. Propensity score matching (PSM) analysis was performed to reduce selection bias. Kaplan-Meier (K-M) survival and Cox regression analyses were conducted before and after PSM to study the survival difference between the two groups. The survival outcome and treatment modality were also investigated in patients with different metastatic patterns. The logistic regression analyses were utilized to determine significant surgery-benefit-related predictors, develop a screening nomogram and its online version, and quantify the beneficial probability of local surgery for BC patients with BM. Receiver operating characteristic (ROC) curves, the area under the curves (AUC), and calibration curves were plotted to evaluate the predictive performance and calibration of this model, whereas decision curve analysis (DCA) was used to assess its clinical usefulness.
This study included 5,625 eligible patients, of whom 2,133 (37.92%) received surgical resection of primary lesions. K-M survival analysis and Cox regression analysis demonstrated that local surgery was independently associated with better survival. Surgery provided significant survival benefits in most subgroups and metastatic patterns. After PSM, patients who received surgery had a longer survival time (OS: 46 months vs. 32 months, p < 0.001; CSS: 50 months vs. 34 months, p < 0.001). Logistic regression analysis determined six significant surgery-benefit-related variables: T stage, radiotherapy, race, liver metastasis, brain metastasis, and breast subtype. These factors were combined to establish the nomogram and a web probability calculator (https://sunshine1.shinyapps.io/DynNomapp/), with an AUC of 0.673 in the training cohort and an AUC of 0.640 in the validation cohort. The calibration curves exhibited excellent agreement. DCA indicated that the nomogram was clinically useful. Based on this model, surgery patients were assigned into two subsets: estimated sur-non-benefit and estimated sur-benefit. Patients in the estimated sur-benefit subset were associated with longer survival (median OS: 64 months vs. 33 months, P < 0.001). Besides, there was no difference in survival between the estimated sur-non-benefit subset and the non-surgery group.
Our study further confirmed the significance of local surgery in BC patients with BM and proposed a novel tool to identify optimal surgical candidates.

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.
CONCLUSIONS: 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.