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European Urology Feb 2024Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Despite the lack of level 1 evidence, metastasis-directed therapy (MDT) is used widely in the management of metastatic prostate cancer (mPCa) patients. Data are continuously emerging from well-designed prospective studies.
OBJECTIVE
To summarise and report the evidence on oncological and safety outcomes of MDT in the management of mPCa patients.
EVIDENCE ACQUISITION
We searched the PubMed, Scopus, and Web of Science databases for prospective studies assessing progression-free survival (PFS), local control (LC), androgen deprivation therapy (ADT)-free survival (ADT-FS), overall survival (OS), and/or adverse events (AEs) in mPCa patients treated with MDT. A meta-analysis was performed for 1- and 2-yr PFS, LC, ADT-FS, OS, and rate of AEs. Meta-regression and sensitivity analysis were performed to account for heterogeneity and identify moderators.
EVIDENCE SYNTHESIS
We identified 22 prospective studies (n = 1137), including two randomised controlled trials (n = 116). Two studies were excluded from the meta-analysis (n = 120). The estimated 2-yr PFS was 46% (95% confidence interval [CI]: 36-56%) or 42% (95% CI: 33-52%) after excluding studies using biochemical or ADT-related endpoints. The estimated 2-yr LC, ADT-FS, and OS were 97% (95% CI: 94-98%), 55% (95% CI: 44-65%), and 97% (95% CI: 95-98%), respectively. Rates of treatment-related grade 2 and ≥3 AEs were 2.4% (95% CI: 0.2-7%) and 0.3% (95% CI: 0-1%), respectively.
CONCLUSIONS
MDT is a promising treatment strategy associated with favourable PFS, excellent LC, and a low toxicity profile that allows oligorecurrent hormone-sensitive patients to avoid or defer ADT-related toxicity. Integration of MDT with other therapies offers a promising research direction, in particular, in conjunction with systemic treatments and as a component of definitive care for oligometastatic PCa. However, in the absence of randomised trials, using MDT for treatment intensification remains an experimental approach, and the impact on OS is uncertain.
PATIENT SUMMARY
Direct treatment of metastases is a promising option for selected prostate cancer patients. It can delay hormone therapy and is being investigated as a way of intensifying treatment at the expense of manageable toxicity.
Topics: Male; Humans; Prostatic Neoplasms; Prospective Studies; Androgen Antagonists; Progression-Free Survival; Hormones
PubMed: 37945451
DOI: 10.1016/j.eururo.2023.10.012 -
Current Opinion in Urology Sep 2023To provide a critical overview of the latest evidence on the role of metastasis-direct treatment (MDT) in the management of metastatic renal cell carcinoma (mRCC). (Review)
Review
PURPOSE OF REVIEW
To provide a critical overview of the latest evidence on the role of metastasis-direct treatment (MDT) in the management of metastatic renal cell carcinoma (mRCC).
RECENT FINDINGS
This is a nonsystematic review of the English language literature published since January 2021. A PubMed/MEDLINE search using various search terms was conducted, including only original studies. After title and abstract screening, selected articles were grouped into two main areas which mirror the main treatment options in this setting: surgical metastasectomy (MS) and stereotactic radiotherapy (SRT). While a limited number of retrospective studies have been reported on surgical MS, the consensus of these reports is that extirpation of metastasis should be part of a multimodal management strategy for carefully selected cases. In contrast, there have been both retrospective studies and a small number of prospective studies on the use of SRT of metastatic sites.
SUMMARY
As the management of mRCC rapidly evolves, and evidence on MDT - both in the form of MS and SRT - has continued to build over the past 2 years. Overall, there is growing interest in this therapeutic option, which is increasingly being implemented and seems to be safe and potentially beneficial in well selected disease scenarios.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Retrospective Studies; Prospective Studies; Combined Modality Therapy
PubMed: 37405715
DOI: 10.1097/MOU.0000000000001111 -
Cancer Biology & Therapy Dec 2023Despite recent advances in cancer therapeutics, pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year overall survival of only 10%. Since either... (Review)
Review
Despite recent advances in cancer therapeutics, pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year overall survival of only 10%. Since either at or within a few months of diagnosis, most patients with PDAC will present with metastatic disease, a more individualized approach to select patients who may benefit from more aggressive therapy has been suggested. Although studies have reported improved survival in PDAC and isolated pulmonary metastasis (ISP) compared to extrapulmonary metastases, such findings remain controversial. Furthermore, the added benefit of pulmonary metastasectomy and other lung-directed therapies remains unclear. In this review, we discuss the metastatic pattern of PDAC, evaluate the available evidence in the literature for improved survival in PDAC and ISP, evaluate the evidence for the added benefit of pulmonary metastasectomy and other lung-directed therapies, identify prognostic factors for survival, discuss the biological basis for the reported improved survival and identify areas for further research.
Topics: Humans; Retrospective Studies; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Lung Neoplasms; Prognosis
PubMed: 37526431
DOI: 10.1080/15384047.2023.2198479 -
Updates in Surgery Oct 2023Laser-assisted resection (LAR) of pulmonary metastases offers several potential advantages compared to conventional surgical techniques. However, the technical details,... (Review)
Review
Laser-assisted resection (LAR) of pulmonary metastases offers several potential advantages compared to conventional surgical techniques. However, the technical details, indications and outcomes of LAR have not been extensively reviewed. We conducted a systematic literature search to identify all original articles reporting on LAR of pulmonary metastases. All relevant outcomes, including morbidity rate, R0 rate, pulmonary function tests, overall- (OS) and relapse-free survival (RFS) rates were collected. Additionally, a comparison between outcomes obtained by laser-assisted and conventional resection techniques was provided. Of 2629 articles found by the initial search, 12 were selected for the systematic review. Following LAR, the R0 rate ranged between 72 and 100% and the morbidity rate ranged from 0 to 27.5%. The postoperative decline in forced expiratory volume in 1 s varied between 3.4 and 11%. Median OS and RFS were 42-77.6 months and 9-34.1 months, respectively. Compared with patients treated by other resection techniques, patients treated by LAR frequently had a higher number of metastases and a higher rate of bilateral disease. Despite this, no significant differences were observed in R0 rate, morbidity rate, and median OS rate, while only 1 study found a lower RFS rate in the LAR cohort. Although selection bias limits the comparability of outcomes, the findings of this review suggest that LAR is a valid alternative to conventional procedures of lung metastasectomy. The main difficulties of this technique consist in the adoption of a video-assisted thoracoscopic approach, and in the pathologic assessment of resection margins.
PubMed: 37347356
DOI: 10.1007/s13304-023-01564-x -
British Journal of Cancer Sep 2023In gastric cancer (GC) patients, metastatic progression through the lymphatic, hematogenous, peritoneal, and ovarian routes, is the ultimate cause of death. However, the...
BACKGROUND
In gastric cancer (GC) patients, metastatic progression through the lymphatic, hematogenous, peritoneal, and ovarian routes, is the ultimate cause of death. However, the genomic and evolutionary characteristics of metastatic GC have not been widely evaluated.
METHODS
Whole-exome sequencing data were analyzed for 99 primary and paired metastatic gastric cancers from 15 patients who underwent gastrectomy and metastasectomy.
RESULTS
Hematogenous metastatic tumors were associated with increased chromosomal instability and de novo gain/amplification in cancer driver genes, whereas peritoneal/ovarian metastasis was linked to sustained chromosomal stability and de novo somatic mutations in driver genes. The genomic distance of the hematogenous and peritoneal metastatic tumors was found to be closer to the primary tumors than lymph node (LN) metastasis, while ovarian metastasis was closer to LN and peritoneal metastasis than the primary tumor. Two migration patterns for metastatic GCs were identified; branched and diaspora. Both molecular subtypes of the metastatic tumors, rather than the primary tumor, and their migration patterns were related to patient survival.
CONCLUSIONS
Genomic characteristics of metastatic gastric cancer is distinctive by routes and associated with patients' prognosis along with genomic evolution pattenrs, indicating that both primary and metastatic gastric cancers require genomic evaluation.
Topics: Female; Humans; Stomach Neoplasms; Lymphatic Metastasis; Prognosis; Genomics; Gastrectomy; Ovarian Neoplasms; Lymph Nodes
PubMed: 37422528
DOI: 10.1038/s41416-023-02338-3 -
Annals of Surgical Oncology Jun 2024Pancreatic ductal adenocarcinoma (PDAC) is most often metastatic at diagnosis. As systemic therapy continues to improve alongside advanced surgical techniques, the focus... (Review)
Review
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.
Topics: Humans; Pancreatic Neoplasms; Metastasectomy; Carcinoma, Pancreatic Ductal; Prognosis; Liver Neoplasms; Lung Neoplasms
PubMed: 38502293
DOI: 10.1245/s10434-024-15129-8 -
The Journal of International Medical... Sep 2023The most common site of metastasis in patients with colon cancer is the liver. This study aimed to identify patients with colon cancer at high risk of developing liver...
OBJECTIVE
The most common site of metastasis in patients with colon cancer is the liver. This study aimed to identify patients with colon cancer at high risk of developing liver metastasis and to explore their prognosis.
METHODS
The clinical characteristics, treatment methods and survival outcomes of patients diagnosed with colon cancer from 2010 to 2015 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Patients were divided into two groups according to the presence of liver metastasis, and multivariate logistic and Cox regression models were used to identify risk and prognostic factors.
RESULTS
A total of 60,018 patients with colon cancer were selected from the SEER database. The incidence of liver metastasis was 9.2%. African American ethnicity, poor differentiation, higher tumor stage, higher lymph node ratio, and lung metastases were common factors associated with both liver metastasis risk and prognosis.
CONCLUSIONS
Metastasectomy might improve survival among patients with colon cancer with resectable liver metastasis lesions and no other organ involvement.
Topics: Humans; Black People; Colonic Neoplasms; Liver Neoplasms; Prognosis; Risk Factors; SEER Program; United States
PubMed: 37737100
DOI: 10.1177/03000605231191580 -
Annals of Surgical Oncology Sep 2023
Topics: Humans; Metastasectomy; Melanoma; Skin Neoplasms; Neoplasm Staging
PubMed: 37326813
DOI: 10.1245/s10434-023-13760-5 -
Journal of Surgical Oncology Sep 2023As the life expectancy of patients with carcinomas improves, there is an associated increase in the risk of development of metastatic bone disease. Patients with... (Review)
Review
As the life expectancy of patients with carcinomas improves, there is an associated increase in the risk of development of metastatic bone disease. Patients with solitary or oligometastatic bone disease of the appendicular skeleton may benefit from metastasectomy and reconstruction to improve overall survival. Specifically, patients with renal cell carcinoma and a solitary metastatic bone lesion will have long-term survival benefit from metastasectomy and reconstruction. There remains controversy in the literature about metastasectomy for solitary metastatic bone disease in other common carcinomas, such as breast and thyroid.
Topics: Humans; Kidney Neoplasms; Metastasectomy; Carcinoma, Renal Cell; Bone Diseases
PubMed: 37537980
DOI: 10.1002/jso.27403 -
Prognostic Factors for Survival in Patients Undergoing Surveillance After Cytoreductive Nephrectomy.The Journal of Urology Aug 2023The clinical course of patients being placed on surveillance in a cohort of systemic therapy-naïve patients who undergo cytoreductive nephrectomy is not well...
PURPOSE
The clinical course of patients being placed on surveillance in a cohort of systemic therapy-naïve patients who undergo cytoreductive nephrectomy is not well documented. Thus, we evaluated the clinical course of patients placed on surveillance following cytoreductive nephrectomy and identified predictors of survival.
MATERIALS AND METHODS
In this large single-institution study, we retrospectively analyzed metastatic renal cell carcinoma patients who underwent cytoreductive nephrectomy followed by surveillance. Predictors of survival were evaluated using the Kaplan-Meier method with a log-rank test. Patients were risk stratified based on IMDC (International mRCC Database Consortium) and number of metastatic sites (Rini score), with IMDC score ≤1 and ≤2 metastatic organ sites considered favorable risk. Primary end point was systemic therapy-free survival. Secondary end points included intervention-free survival, cancer-specific survival, and overall survival.
RESULTS
Median systemic therapy-free survival was 23.6 months (95% CI: 15.1-40.6), intervention-free survival was 11.8 months (95% CI: 8.0-18.4), cancer-specific survival was 54.2 months (95% CI: 46.2-71.4), and overall survival 52.4 months (95% CI: 40.3-66.8). Favorable-risk patients compared to unfavorable-risk patients had longer systemic therapy-free survival (50.6 vs 11.1 months, < .01), survival (25.2 vs 7.3, < .01), and cancer-specific survival (71.4 vs 46.2 months, = .02).
CONCLUSIONS
Using risk stratification based on IMDC and number of metastatic sites, surveillance in favorable-risk patients can be utilized for a period without the initiation of systemic therapy. This approach can delay patients' exposure to the side effects of systemic therapy.
Topics: Humans; Carcinoma, Renal Cell; Kidney Neoplasms; Prognosis; Retrospective Studies; Cytoreduction Surgical Procedures; Nephrectomy; Disease Progression
PubMed: 37167628
DOI: 10.1097/JU.0000000000003549