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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 -
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 -
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 -
BioRxiv : the Preprint Server For... Aug 2023Sarcomas are a family of rare malignancies composed of over 100 distinct histological subtypes. The rarity of sarcoma poses significant challenges in conducting clinical...
UNLABELLED
Sarcomas are a family of rare malignancies composed of over 100 distinct histological subtypes. The rarity of sarcoma poses significant challenges in conducting clinical trials to identify effective therapies, to the point that many rarer subtypes of sarcoma do not have standard-of-care treatment. Even for established regimens, there can be substantial heterogeneity in responses. Overall, novel, personalized approaches for identifying effective treatments are needed to improve patient out-comes. Patient-derived tumor organoids (PDTOs) are clinically relevant models representative of the physiological behavior of tumors across an array of malignancies. Here, we use PDTOs as a tool to better understand the biology of individual tumors and characterize the landscape of drug resistance and sensitivity in sarcoma. We collected n=194 specimens from n=126 sarcoma patients, spanning 24 distinct subtypes. We characterized PDTOs established from over 120 biopsy, resection, and metastasectomy samples. We leveraged our organoid high-throughput drug screening pipeline to test the efficacy of chemotherapeutics, targeted agents, and combination therapies, with results available within a week from tissue collection. Sarcoma PDTOs showed patient-specific growth characteristics and subtype-specific histopathology. Organoid sensitivity correlated with diagnostic subtype, patient age at diagnosis, lesion type, prior treatment history, and disease trajectory for a subset of the compounds screened. We found 90 biological pathways that were implicated in response to treatment of bone and soft tissue sarcoma organoids. By comparing functional responses of organoids and genetic features of the tumors, we show how PDTO drug screening can provide an orthogonal set of information to facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes in sarcoma. In aggregate, we were able to identify at least one effective FDA-approved or NCCN-recommended regimen for 59% of the specimens tested, providing an estimate of the proportion of immediately actionable information identified through our pipeline.
HIGHLIGHTS
Standardized organoid culture preserve unique sarcoma histopathological featuresDrug screening on patient-derived sarcoma organoids provides sensitivity information that correlates with clinical features and yields actionable information for treatment guidanceHigh-throughput screenings provide orthogonal information to genetic sequencingSarcoma organoid response to treatment correlates with patient response to therapyLarge scale, functional precision medicine programs for rare cancers are feasible within a single institution.
PubMed: 37292676
DOI: 10.1101/2023.05.25.542375 -
Cancers Oct 2023Pulmonary metastasectomy and stereotactic ablative radiotherapy (SABR) are both guideline-recommended treatments for selected patients with oligometastatic colorectal...
BACKGROUND
Pulmonary metastasectomy and stereotactic ablative radiotherapy (SABR) are both guideline-recommended treatments for selected patients with oligometastatic colorectal pulmonary metastases. However, there is limited evidence comparing these local treatment modalities in similar patient groups.
METHODS
We retrospectively reviewed records of consecutive patients treated for colorectal pulmonary metastases with surgical metastasectomy or SABR from 2012 to 2019 at two Dutch referral hospitals that had different approaches toward the local treatment of colorectal pulmonary metastases, one preferring surgery, the other preferring SABR. Two comparable patient groups were identified based on tumor and treatment characteristics.
RESULTS
The metastasectomy group comprised 40 patients treated for 69 metastases, and the SABR group had 60 patients who were treated for 90 metastases. Median follow-up was 38 months (IQR: 26-67) in the surgery group and 46 months (IQR: 30-79) in the SABR group. Median OS was 58 months (CI: 20-94) in the metastasectomy group and 70 months (CI: 29-111) in the SABR group ( = 0.23). Five-year local recurrence-free survival (LRFS) was 44% after metastasectomy and 30% after SABR ( = 0.16). Median progression-free survival (PFS) was 15 months (CI: 3-26) in the metastasectomy group and 10 months (CI: 6-13) in the SABR group ( = 0.049). Local recurrence rate was 12.5/7.2% of patients/metastases respectively after metastasectomy and 38.3/31.1% after SABR ( < 0.001). Lower BED Gy was correlated with an increased likelihood of recurrence ( = 0.025). Clavien Dindo grade III-V complication rates were 2.5% after metastasectomy and 0% after SABR ( = 0.22).
CONCLUSION
In this retrospective cohort study, pulmonary metastasectomy and SABR had comparable overall survival, local recurrence-free survival, and complication rates, despite patients in the SABR group having a significantly lower progression-free survival and local control rate. These data would support a randomized controlled trial comparing surgery and SABR in operable patients with radically resectable colorectal pulmonary metastases.
PubMed: 37958360
DOI: 10.3390/cancers15215186 -
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 -
Cancers Apr 2024Colorectal cancer is the third-most-diagnosed cancer in males and in females, representing 8% of estimated new cases, and the third cause of cancer-related death in both... (Review)
Review
Colorectal cancer is the third-most-diagnosed cancer in males and in females, representing 8% of estimated new cases, and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9-12% are eligible for local treatments with radical intent, including surgical resection, SBRT (stereotactic body radiation therapy) and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.
PubMed: 38611086
DOI: 10.3390/cancers16071408 -
Interdisciplinary Cardiovascular and... Mar 2024Information on prognostic factors after repeat pulmonary metastasectomy (PM) is limited, and outcomes after a third PM are not well documented.
OBJECTIVES
Information on prognostic factors after repeat pulmonary metastasectomy (PM) is limited, and outcomes after a third PM are not well documented.
METHODS
A single-institute retrospective study was conducted. Between 2000 and 2020, 68 patients underwent repeat PM for pulmonary metastases from various cancers. Outcomes and prognostic factors for the second PM and outcomes after the third PM were analysed.
RESULTS
This study included 39 men and 29 women. The mean age at second PM was 53.2 years old. The primary tumours were soft tissue sarcoma in 24 patients, colorectal cancer in 19 and osteosarcoma in 10. The interval between the first PM procedure and detection of pulmonary metastasis after the first PM (months) was ≤12 in 37 patients and >12 in 31 patients. At the second PM, 20 patients underwent lobectomy or bilobectomy, and 48 underwent sublobar resection. Complete resection was achieved in 60 patients, and 52 patients experienced recurrence after the second PM. The 5-year relapse-free survival and overall survival rates after the second PM were 27% and 48%, respectively. Multivariable analysis revealed that the interval between the first PM and the subsequent detection of pulmonary metastasis (≤12 months) was a poor prognostic factor for both relapse-free survival and overall survival after the second PM. Seventeen patients underwent a third PM, 3 of whom achieved a 3-year disease-free survival.
CONCLUSIONS
Patients with a period of >12 months between the first PM and the subsequent detection of pulmonary metastases showed favourable outcomes and are thus considered good candidates for second PM. A third PM may be beneficial for selected patients.
PubMed: 38426364
DOI: 10.1093/icvts/ivae028 -
Cancer Medicine Oct 2023Thoracotomy is considered the standard surgical approach for the management of pulmonary metastases in osteosarcoma (OST). Several studies have identified the advantages... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Thoracotomy is considered the standard surgical approach for the management of pulmonary metastases in osteosarcoma (OST). Several studies have identified the advantages of a thoracoscopic approach, however, the clinical significance of thoracotomy compared to thoracoscopy is yet to be evaluated in a randomized trial.
AIMS
The primary aim was to determine the survival outcomes in OST patients based on surgical approach for pulmonary metastasectomy (PM) and secondary aim was to assess the post-operative morbidities of OST PM through various surgical approaches.
MATERIALS AND METHODS
We conducted a single institution retrospective study to compare survival outcomes and surgical morbidity according to the surgical approach of the management of pulmonary metastases in patients with OST.
RESULTS
Sixty-one patients with OST underwent PM. Twenty-one patients were metastatic at diagnosis and underwent PM during primary treatment; nine had thoracotomy, six thoracoscopy, and six combined thoracoscopy with thoracotomy (CTT). Forty-three patients with first pulmonary relapse or progression underwent PM; 18 had thoracotomy, 16 thoracoscopy and nine CTT. There was no difference in survival between surgical approaches. There were significantly more postoperative morbidities associated with thoracotomy for initial PM (pain and postoperative chest tube placement), and for PM at first relapse (pneumothoraces, pain, Foley catheter use and prolonged hospitalizations).
CONCLUSION
Our study demonstrates that patients with OST pulmonary metastases have comparable poor outcomes despite varying surgical approaches for PM. There were significantly more postoperative morbidities associated with thoracotomy for PM. Surgical bias and other competing risks could not be assessed given the limitations of a retrospective study and may be addressed in a prospective trial evaluating surgical approach for PM in OST.
Topics: Humans; Child; Adolescent; Young Adult; Metastasectomy; Retrospective Studies; Prospective Studies; Lung Neoplasms; Osteosarcoma; Bone Neoplasms; Morbidity; Pain; Recurrence; Thoracotomy
PubMed: 37800658
DOI: 10.1002/cam4.6491