Multicentre retrospective analysis on pulmonary metastasectomy: an European perspective.

OBJECTIVES: To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS: Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS: A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25-75% = 1-2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS: Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice.

Is there a role for metastasis-directed therapy in bladder cancer?

PURPOSE OF REVIEW: This article aims to comprehensively review and critique the existing literature on the role of metastatic-directed therapy in patients with metastatic bladder cancer, particularly in oligometastatic disease state. RECENT FINDINGS: The role of metastasectomy in metastatic bladder cancer is still controversial. Several studies have demonstrated improved outcomes, particularly in a highly selected patients with small metastatic lesions or with lung or brain metastases, whereas others show no significant survival benefit. Combining metastasectomy with systemic therapies, such as immunotherapy and chemotherapy, has also shown benefits. Metastasis-directed radiotherapy is evolving as a potentially effective approach with minimal toxicity in achieving local control and improving survival, particularly in patients with oligometastatic disease. The evidence regarding the impact of several factors such as performance status, metastatic burden, and the presence of visceral metastases on outcomes is mixed. Concurrent treatment with systemic therapy may potentiate the effectiveness of metastasis-directed therapy. SUMMARY: In patients with metastatic deposits amenable to surgical resection, metastasectomy stands as a promising avenue. Metastatic-directed radiotherapy has demonstrated local control and improved survival in the evolving landscape of oligometastatic bladder cancer management. Further, well designed multicenter prospective studies are needed to support these findings and better understand the synergy between radiotherapy and systemic treatments, especially immunotherapy.

Definitions and unmet needs in the management of oligomestatic renal cell carcinoma in the modern era.

PURPOSE OF REVIEW: Oligometastatic renal cell carcinoma (RCC) is a complex entity, potentially leading to a specific clinical management of these patients. Recent and ongoing trials have raised several unresolved questions that could impact clinical routine practice, advocating for the integration of novel treatment options (systemic treatment, cytoreductive surgery, or stereotactic body radiotherapy - SBRT) with varied modalities and objectives. RECENT FINDINGS: Immunotherapy represents a breakthrough in the systemic treatment of mRCC. However, many questions are still unsolved regarding the perfect timing for starting systemic and whether the systemic treatment could improve the activity of metastases-directed strategies. Moreover, the widespread use of adjuvant immunotherapy will challenge the treatment paradigm in the oligorecurrent scenario. Radical surgery of metastases and more recently SBRT - both eventually associated with systemic treatment - actually represent two important approaches to be considered in oligometastatic patients. SUMMARY: Oligometastatic RCC represents a status including a wide spectrum of clinical conditions that requires a tailored treatment approach. The correct management integrates local approaches (either metastasectomy or SRBT) and systemic (immune)-therapy. Several unmet needs have to be investigated, mainly regarding the lack of prospective randomized trials that directly compare modern therapies and different integration strategies.

Surgery for Oligometastatic Pancreatic Cancer: Defining Biologic Resectability.

Pancreatic ductal adenocarcinoma (PDAC) is most often metastatic at diagnosis. As systemic therapy continues to improve alongside advanced surgical techniques, the focus has shifted toward defining biologic, rather than technical, resectability. Several centers have reported metastasectomy for oligometastatic PDAC, yet the indications and potential benefits remain unclear. In this review, we attempt to define oligometastatic disease in PDAC and to explore the rationale for metastasectomy. We evaluate the existing evidence for metastasectomy in liver, peritoneum, and lung individually, assessing the safety and oncologic outcomes for each. Furthermore, we explore contemporary biomarkers of biological resectability in oligometastatic PDAC, including radiographic findings, biochemical markers (such as CA 19-9 and CEA), inflammatory markers (including neutrophil-to-lymphocyte ratio, C-reactive protein, and scoring indices), and liquid biopsy techniques. With careful consideration of existing data, we explore the concept of biologic resectability in guiding patient selection for metastasectomy in PDAC.

Prolonged survival after thoracic metastasectomy in patients with nonseminomatous testicular cancer.

INTRODUCTION: Almost 20 % of patients with Non-Seminomatous Germinative Cell Tumors (NSGCT) will require intrathoracic metastasectomy after chemotherapy. The authors aim to determine their long-term survival rates. METHODS: Retrospective study including patients with NSGCT and intrathoracic metastasis after systemic therapy from January 2011 to June 2022. Treatment outcomes and overall survival were analyzed with the Kaplan-Meier method. RESULTS: Thirty-seven male patients were included with a median age of 31.8 years. Six presented with synchronous mediastinum and lung metastasis, nine had only lung, and 22 had mediastinal metastasis. Over half had retroperitoneal lymph node metastasis. Twenty-two had dissimilar pathologies, with a discordance rate of 62 %. Teratoma and embryonal carcinoma were the prevalent primary tumor types, 40.5 % each, while teratoma was predominant (70.3 %) in the metastasis group. Thoracotomy was the main surgical approach (39.2 %) followed by VATS (37.2 %), cervico-sternotomy (9.8 %), sternotomy (5.8 %), and clamshell (3.9 %). Lung resection was performed in 40.5 % of cases. Overall, 10-year survival rates were 94.3 % with no surgical-related mortality. CONCLUSION: Multimodality treatment with systemic therapy followed by radical surgery offers a high cure rate to patients with intrathoracic metastatic testicular germ cell tumors.

Do Children With Osteosarcoma Benefit From Pulmonary Metastasectomy?: A Systematic Review of Published Studies and "Real World" Outcomes.

OBJECTIVE: To critically examine the evidence-base for survival benefit of pulmonary metastasectomy (PM) for osteosarcoma (OS) in the pediatric population. BACKGROUND: PM for OS is recommended as the standard of care in both pediatric and adult treatment protocols. Recent results from the "Pulmonary Metastasectomy in Colorectal Cancer" trial demonstrate no survival benefit from PM in colorectal cancer in adults. METHODS: A systematic review was undertaken according to "Preferred Reporting Items for Systematic Reviews and Meta-Analysis" guidelines. Medline, Embase, and 2 clinical trial registers were searched for all studies detailing pediatric patients with OS (<18 years) undergoing PM with a comparison cohort group that did not receive PM. RESULTS: Eleven studies met inclusion criteria dating from 1984 to 2017. All studies were retrospective and none directly compared PM versus no PM in pediatric patients as its main objective(s). Three-year survival rates ranged from 0% to 54% for PM and 0% to 16% for no PM. No patients receiving PM were usually those with unresectable disease and/or considered to have a poor prognosis. All studies were at high risk of bias and there was marked heterogeneity in the patient selection. CONCLUSIONS: There is a weak evidence base (level IV) for a survival benefit of PM for OS in pediatric patients likely due to selection bias of "favorable cases." The included studies many of which detailed outdated treatment protocols were not designed in their reporting to specifically address the questions directly. A randomized controlled trial-while ethically challenging in a pediatric population-incorporating modern OS chemotherapy protocols is needed to crucially address any "survival benefit."

Surgical metastasectomy for metastatic renal cell carcinoma in the era of targeted and immune therapy: a narrative review.

PURPOSE: Metastatic renal cell carcinoma (mRCC) still harbours a big propensity for future metastasis. Combinations of immune and targeted therapies are currently the cornerstone of management with a less clear role for surgical metastasectomy (SM). METHODS: We performed a narrative review of literature searching for the available evidence on the yield of surgical metastasectomy in the era of targeted and immune therapies. The review consisted of a PubMed search of relevant articles using the Mesh terms:" renal cell carcinoma", "surgery¼, «resection", "metastasectomy", "molecular targeted therapies", "immune checkpoint inhibitors" alone or in combination. RESULTS: In this review, we exposed the place of surgical metastasectomy within a multimodal treatment algorithm for mRCC Also, we detailed the patient selection criteria that yielded the best results when SM was performed. Finally, we discussed the feasibility and advantages of SM per organ site. CONCLUSION: Our work was able to show that SM could be proposed as a consolidation treatment to excise residual lesions that were deemed unresectable prior to a combination of systemic therapies. Contrastingly, it can be proposed as an upfront treatment, leaving systemic therapies as an alternative in case of future relapse. However, patient selection regarding their performance status, metastatic sites, number of lesions and tumorous characteristics is of paramount importance.

Lung surveillance following colorectal cancer pulmonary metastasectomy: Utilization of clinicopathologic risk factors to guide strategy.

BACKGROUND: Appropriately selected patients clearly benefit from resection of colorectal cancer (CRC) pulmonary metastases (PMs). However, there remains equipoise surrounding optimal chest surveillance strategies following pulmonary metastasectomy. We aimed to identify risk factors that may inform chest surveillance in this population. METHODS: Patients who underwent CRC pulmonary metastasectomy were identified from a single institution's prospectively maintained surgical database. Clinicopathologic and genomic characteristics were collected. Patients were stratified by diagnosis of subsequent PM within 6 months of the index lung resection. Multivariate modeling was used to evaluate risk factors. RESULTS: A total of 197 patients met the study's inclusion criteria, of whom 52.3% (n = 103) developed subsequent PM, at a median of 9.51 months following the index metastasectomy. Patients with KRAS alterations (odds ratio [OR], 3.073; 95% confidence interval [CI], 1.363-6.926; P = .007), TP53 alterations (OR, 3.109; 95% CI, 1.318-7.341; P = .010) were found to be at risk of PM diagnosis within 6 months of the index metastasectomy, while those with an APC alteration (OR, .218; 95% CI, 0.080-0.598; P = .003) were protected. Moreover, patients who received systemic therapy within 3 months of the initial PM diagnosis also were more likely to develop early lung recurrence (OR, 2.105; 95% CI, 0.971-4.563; P = .059). CONCLUSIONS: Patients with KRAS alterations, TP53 alterations, and no APC alterations developed early recurrence in the lung following pulmonary metastasectomy, as did those who received chemotherapy after their initial PM diagnosis. As such, these groups benefit from early lung imaging after metastasectomy, as chest surveillance protocols should be based on patient-centered clinicopathologic and genomic risk factors.

Effect of metastasectomy on the outcome of patients with ovarian metastasis of colorectal cancer: A systematic review and meta-analysis.

PURPOSE: Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to evaluate the prognostic value of ovarian metastasectomy and other factors in CROM patients. METHODS: We searched literature up to November 1, 2021 in MEDLINE (PubMed), Embase, Cochrane Library, and Clinicaltrials.gov. Retrospective studies were assessed if survival outcome of CROM patients was reported. Results were pooled in a random-effects model and reported as hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity was analyzed. RESULTS: Among 2497 studies screened, 15 studies with 997 patients, published between 2000 and 2021, were included. Longer overall survival (OS) was correlated with ovarian metastasectomy (pooled HR = 0.44, 95% CI: 0.34-0.58, P < 0.05) and R0 resection (pooled HR = 0.26, 95% CI: 0.16-0.41, P < 0.05). Longer disease-specific survival (DSS) was associated with systematic chemotherapy (pooled HR = 0.26, 95% CI: 0.15-0.45, P < 0.0001). Shorter OS was associated with extraovarian metastases (pooled HR = 3.00, 95% CI 1.68-5.36, P < 0.05) and bilateral OM (pooled HR = 1.66, 95% CI: 1.09-2.51, P < 0.05). No significant difference in OS was observed among patients with systematic chemotherapy (pooled HR = 0.68, 95% CI: 0.35-1.31, P > 0.05). CONCLUSION: Metastasectomy achieving R0 resection can significantly prolong OS and DSS of CROM patients as a reasonable treatment modality. Primary tumor resection and systematic chemotherapy can improve patients' outcomes. REGISTRATION NUMBER: CRD42022299185 (http://www.crd.york.ac.uk/PROSPERO).

Adrenal Metastasectomy in the Era of Immuno- and Targeted Therapy.

Adrenal metastasectomy has an increasing role in multimodality oncologic care for diverse primary cancer types. In this review, we discuss the epidemiology, evaluation, and contemporary best practices in the management of adrenal metastases from various primaries. Initial evaluation of suspected adrenal metastases should include diagnostic imaging to assess the extent of tumor involvement and determine surgical resectability, as well as biochemical evaluation for hormone secretion. Biopsy has a minimal role and should only be performed in tumors that are established to be non-hormone secreting and when the biopsy results would change clinical management. Adrenal metastasectomy is associated with survival benefit in selected patients. We suggest that adrenal metastasectomy has the greatest benefit in four clinical scenarios: (1) disease limited to the adrenal gland in which adrenalectomy renders the patient disease-free; (2) isolated progression in the adrenal gland in the setting of otherwise controlled metastatic extra-adrenal disease; (3) need for palliation of symptoms related to adrenal metastases; or (4) in the context of tissue-based clinical trials. Both minimally invasive and open adrenalectomy techniques are safe and appear to have equivalent oncologic outcomes. Minimally invasive approaches are favored when technically feasible while maintaining oncologic principles. A multidisciplinary evaluation including clinicians with expertise in the primary cancer type is essential to the successful management of adrenal metastases.

Improving survival after pulmonary metastasectomy for sarcoma: analysis of prognostic factors.

BACKGROUND: Metastatic sarcoma confers a grave prognosis to patients and poses a management dilemma for clinicians. Pulmonary metastasectomy is frequently performed for the recurrence of sarcomatous tumours in the lung, but the evidence-base is poor. No guidelines exist to inform clinicians on appropriate patient selection and surgical technique. AIM: This review aims to establish and analyse the most important prognostic factors for survival post pulmonary metastasectomy for recurrent sarcoma. We summarise the key tumour, peri-operative and patient characteristics that should guide surgical management. METHODS: A comprehensive search of the literature utilising OVID Medline and PubMed databases was conducted to identify all relevant research within the past 15 years. We evaluated all articles that specifically studied sarcoma patients (both bone and soft tissue). CONCLUSION: Disease-free interval and tumour burden remain important prognostic factors, while tumour grade is likely not significant. VATS is a safe and viable alternative to thoracotomy without sacrificing survival outcomes. No single peri-operative characteristic provides useful prognostic information in isolation.

International Multi-institutional Characterization of the Perioperative Morbidity of Metastasectomy for Renal Cell Carcinoma.

BACKGROUND: Surgical resection of metastatic renal cell carcinoma (mRCC) has been associated with better cancer-specific survival; however, high-quality data on its perioperative morbidity are lacking. Existing population-based data are severely limited by reliance on billing claims to identify outcomes, which may overestimate events owing to a lack of code specificity. OBJECTIVE: To study 30-d complications after metastasectomy for mRCC. DESIGN, SETTING, AND PARTICIPANTS: The study involved a retrospective cohort of patients who underwent metastasectomy for mRCC between 2005 and 2020 at two high-volume centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used generalized estimating equations for a binary response to evaluate associations of features with 30-d complications classified according to Clavien-Dindo grade. RESULTS AND LIMITATIONS: A total of 740 metastasectomies in 522 patients were identified, including 543 performed in the Mayo Clinic and 197 in UZ Leuven. Among the 740 metastasectomies, 193 (26%, 95% confidence interval [CI] 23-29%) had a 30-d complication and 62 (8%, 95% CI 7-11%) had a major (Clavien-Dindo III-V) complication, including eight (1%) perioperative deaths. Age, body mass index, American Society of Anesthesiologists score, metastasectomy concurrent with nephrectomy, multiple sites of metastasis, pancreatic resection, and metastasis size were significantly associated with postoperative complications (all p < 0.05). Age, multiple sites of metastasis, and pancreatic resection were significantly associated with major (Clavien-Dindo III-V) complications (all p < 0.05). Limitations include the retrospective design and surgical selection bias. CONCLUSIONS: In this multi-institutional series, fewer than 10% of metastasectomies for mRCC resulted in a major complication within 30 d of surgery, which is considerably lower than previously observed in population-based data. Favorable perioperative outcomes can be achieved with metastasectomy at high-volume centers in well-selected patients. PATIENT SUMMARY: In this study we found that fewer than 10% of patients who underwent surgical removal of one or more sites of metastatic kidney cancer experienced a major complication within 30 days of surgery.

Surgical Metastasectomy for Visceral and Bone Prostate Cancer Metastases: A Mini-Review.

Despite growing interest in metastasis-directed therapy (MDT) for prostate cancer (PCa), little is known regarding the feasibility and effectiveness of surgical metastasectomy for isolated lesions. We performed a narrative review of the available evidence supporting metastasectomy for M1b-c lesions in men diagnosed with oligometastatic or oligorecurrent PCa. The case series and case reports we identified indicate that surgical MDT is a safe and feasible treatment option for well-selected patients with a small number of PCa metastases diagnosed via molecular imaging. It is difficult to draw evidence-based conclusions regarding the survival benefit of metastasectomy; however, metastasectomy might lead to a prostate-specific antigen response and could potentially delay systemic therapy in patients with oligometastatic PCa. Prospective studies incorporating novel imaging are needed to better establish the role of metastasectomy for patients with metastatic PCa. PATIENT SUMMARY: We reviewed the evidence on surgical removal of prostate cancer lesions that have spread to the organs (eg, liver and lung) or bone, which are called metastases. Limited results show that this approach is feasible and has favorable outcomes in selected patients.

Repeated Pulmonary Metastasectomy: Third Operations and Beyond.

BACKGROUND: For extrathoracic malignant neoplasms that have metastasized to the lungs, previous investigations have demonstrated both oncologic and survival benefits after pulmonary and repeated metastasectomy. Little is known about the feasibility of incrementally increasing numbers of subsequent metastasectomy procedures. METHODS: We conducted a retrospective review of patients who underwent ≥3 pulmonary resection procedures for recurrent, metachronous metastatic disease of nonlung primary malignant neoplasms at a single institution between 1992 and 2020. Primary outcomes collected pertained to safety and feasibility, including estimated blood loss (EBL), hospital length of stay, and details of postoperative complications. RESULTS: There were 117 patients who met inclusion criteria, having undergone at least 3 metastasectomy operations, with 55 (47.1%) undergoing a fourth operation and 20 (17.1%) undergoing a fifth operation. EBL did not differ between first and second operations (106.6 mL vs 102.5 mL; P = .76). It was, however, significantly greater at third operations (102.5 mL vs 238.7 mL; P = .000016). We noted an increase in wound complications between the second and third operations (0.9% vs 6.8%; P = .02) and incremental increases in likelihood of prolonged air leak with each subsequent operation. The need for reoperation was low for all and similar between operations. Importantly, hospital length of stay was similar for all procedures, as were the frequencies of hospital readmission. CONCLUSIONS: Third-time redo pulmonary metastasectomy can be performed safely and feasibly in select patients. Further repeated resection should remain a therapeutic option for patients, although risks for potentially longer operating time, greater EBL, and prolonged air leaks may be anticipated.

Lung Metastatectomy: Can Laser-Assisted Surgery Make a Difference?

BACKGROUND: Resection of lung metastases with curative intention in selected patients is associated with prolonged survival. Laser-assisted resection of lung metastases results in complete resection of a high number of lung metastases, while preserving lung parenchyma. However, data concerning laser lung resections are scarce and contradictory. The aim of this study was to conduct a systematic review to evaluate the utility of laser-assisted pulmonary metastasectomy. METHODS: An electronic search in MEDLINE (via PubMed), complemented by manual searches in article references, was conducted to identify eligible studies. RESULTS: Fourteen studies with a total of 1196 patients were included in this metanalysis. Laser-assisted surgery (LAS) for lung metastases is a safe procedure with a postoperative morbidity up to 24.2% and almost zero mortality. LAS resulted in the resection of a high number of lung metastases with reduction of the lung parenchyma loss in comparison with conventional resection methods. Survival was similar between LAS and conventional resections. CONCLUSION: LAS allows radical lung-parenchyma saving resection of a high number of lung metastases with similar survival to conventional methods.

Metastasectomy in renal cell carcinoma: where are we now?

PURPOSE OF REVIEW: Metastatic RCC has a variable natural history. Treatment choice depends on disease and patient factors, but most importantly disease burden and site of metastasis. This article highlights key variables to consider when contemplating metastasectomy for RCC and provide a narrative review on the evidence for metastasectomy in these patients. RECENT FINDINGS: Tumour subtype is associated with differing patterns of recurrence. Patients with single or few metastatic sites have better outcomes, and those with greater time interval from initial nephrectomy. Local recurrence is particularly amenable to minimally invasive surgical resection and is oncologically sound. Very well selected cases of liver or brain metastases may benefit from metastectomy, although lung and endocrine metastases have more favourable outcomes. Although site and burden of disease is important, the key determinate of outcome in metastasectomy depends mostly on the ability to achieve a complete resection. Adjuvant treatment is not currently advocated. SUMMARY: Metastasectomy should be generally reserved for cases where complete resection is achievable, unless the goal of treatment is to palliate symptoms. This field warrants ongoing research, particularly as systemic therapy and minimally invasive surgical techniques evolve. Elucidating tumour biology to inform patient selection will be important in future research.

Patients with Pulmonary Metastases from Head and Neck Cancer Benefit from Pulmonary Metastasectomy, A Systematic Review.

Background and Objectives: The incidence of distant metastases in patients with head and neck cancer (HNC) is approximately 10%. Pulmonary metastases are the most frequent distant location, with an incidence of 70-85%. The standard treatment options are chemo-, immuno- and radiotherapy. Despite a benefit for long-term survival for patients with isolated pulmonary metastases, pulmonary metastasectomy (PM) is not the treatment of choice. Furthermore, many otorhinolaryngologists are not sufficiently familiar with the concept of PM. This work reviews the recent studies of pulmonary metastatic HNC and the results after pulmonary metastasectomy. Materials and Methods: PubMed, Medline, Embase, and the Cochrane library were checked for the case series' of patients undergoing metastasectomy with pulmonary metastases published since 1 January 2000. Results: We included the data of 15 studies of patients undergoing PM. The 5-year survival rates varied from 21% to 59%, with median survival from 10 to 77 months after PM. We could not identify one specific prognostic factor for long-term survival after surgery. However, at least most studies stated that PM should be planned if a complete (R0) resection is possible. Conclusions: PM showed reliable results and is supposedly the treatment of choice for patients with isolated pulmonary metastases. Patients not suitable for surgery may benefit from other non-surgical therapy. Every HNC patient with pulmonary metastases should be discussed in the multidisciplinary tumor board to optimize the therapy and the outcome.

Can patients with gallbladder adenocarcinoma and liver metastases obtain survival benefit from surgery? A population-based study.

According to international guidelines, surgical treatment is not recommended for gallbladder adenocarcinoma with liver metastases (GCL), and research on the clinical implications of surgery in GCL is very scarce. In this study, we aimed to investigate whether surgery is an effective means to improve survival in GCL. Data were collected from the Surveillance, Epidemiology, and End Results database. A total of 612 people diagnosed with GCL were identified. According to their treatment, patients were categorised into 4 groups: synchronous resection of the primary tumour and liver metastases (SPL), synchronous primary site and other resection (SPO), single resection of the primary site (SPS), and no resection (NR). Our study findings showed that 34 (5.6%) patients received SPL, 18 (2.9%) had SPO, 185 (30.2%) underwent SPS, and 375 (61.3%) received NR. Our analysis showed that surgical treatment was an independent protective prognostic factor for gallbladder cancer cause-specific survival. Groups who underwent SPL, SPO, and SPS showed gradually decreasing survival benefit compared with the NR group (median survival: 9, 5, 4, and 2 months, respectively). Notably, mortality in the SPL, SPO, and SPS groups were significantly different compared with NR group, and the hazard ratio were gradually increased, which were 0.402 (95% confidence interval [CI] 0.264-0.611), 0.463 (95% CI 0.274-0.784), and 0.597 (95% CI 0.457-0.779), respectively (all P < 0.05). Survival in patients with GCL was significantly improved via surgery of the primary site with simultaneous metastasectomy. Among them, SPL and SPO showed greater survival advantages in carefully selected patients with GCL. Registered at researchregistery.com: Trial registration number is researchregistry6915.