Epidemiology, treatment patterns, and clinical outcomes in de novo oligometastatic hormone-sensitive prostate cancer.

BACKGROUND: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone-sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System. METHODS: In this observational retrospective cohort study, 400 de novo metastatic hormone-sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow-up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan-Meier methods estimated overall survival (OS) and castration-resistant prostate cancer (CRPC)-free survival from mHSPC diagnosis date and a log-rank test compared these outcomes by oligometastatic status. RESULTS: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non-omHSPC had higher median prostate-specific antigen at diagnosis (151.7) than omHSPC (44.1). First-line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non-omHSPC (14%). More omHSPC patients received metastasis-directed therapy/prostate radiation therapy (14%) versus non-omHSPC (2%). Median OS and CRPC-free survival (in months) were higher in omHSPC versus non-omHSPC (44.4; 95% confidence interval [CI], 33.9-not estimated vs. 26.2; 95% CI, 20.5-32.5, p = .0089 and 27.6; 95% CI, 22.1-37.2 vs. 15.3; 95% CI, 12.8-17.9, p = .0049), respectively. CONCLUSIONS: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non-omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non-omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies.

Management of oligometastatic and oligoprogressive epidermal growth factor receptor mutated non-small cell lung cancer patients: state of the art of a combined approach.

Recently, the development of targeted therapy approaches such as those based on tyrosine kinase inhibitor (TKI) greatly improved the clinical outcomes of patients affected by oncogene addicted advanced non-small cell lung cancer (NSCLC). Similarly, the improvement of radiation therapy techniques has permitted to deliver high radiation doses to a limited number of metastatic target lesions (oligopersistent or oligoprogressive), with limited high-dose normal tissue exposure that leads to low severe toxicity rates. The aim of this narrative review was to provide an overview of the currently established definition of oligometastatic and oligoprogressive disease, to define first line and subsequent lines targeted therapies and the role of consolidative non-invasive local ablative treatments (LATs) in these settings. The potential benefit of local treatment (LT) such as radiotherapy (RT) or surgery might be represented by an overall reduction of switching to subsequent systemic treatments lowering the risk of further systemic dissemination. Further randomized clinical trials will clarify the role of LT and their correct timing in relation to systemic targeted therapies.

Stereotactic Radiosurgery with Volumetric Modulated Arc Radiotherapy: Final Results of a Multi-arm Phase I Trial (DESTROY-2).

AIMS: To present the final results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumors in different extracranial sites. MATERIALS AND METHODS: The DESTROY-2 trial, planned as a prospective dose escalation study in oligometastatic (one to five lesions) cancer patients relied on the delivery of a single high dose of radiation utilizing high-precision technology. The primary study endpoint was the definition of the maximum tolerated dose (MTD) of SRS-VMAT. The secondary objectives of the study were the evaluation of safety, efficacy, and long-term outcomes. All patients consecutively observed at our radiotherapy unit matching the inclusion criteria were enrolled. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, other), and sequentially assigned to a particular dose level. RESULTS: Two hundred twenty seven lesions in 164 consecutive patients (male/female: 97/67, median age: 68 years; range: 29-92) were treated. The main primary tumors were: prostate cancer (60 patients), colorectal cancer (47 patients), and breast cancer (39 patients). The maximum planned dose level was achieved in all study arms, and the MTD was not exceeded. 34 Gy, 32 Gy, 24 Gy, and 24 Gy were established as the single-fraction doses for treating lung, liver, bone, and other extracranial lesions, respectively. The prescribed BED 2Gyα/ß:10 to the planning target volume ranged from 26.4 Gy to 149.6 Gy. Twenty-seven patients (16.5%) experienced grade 1-2 and only one grade 3 acute toxicity, which was a pulmonary one. In terms of late toxicity, we registered only 5 toxicity>G2: a G3 gastro-intestinal one, three G3 bone toxicity, and a G3 laryngeal toxicity. The overall response was available for 199 lesions: 107 complete response (53.8%), 50 partial response (25.1%), and 31 stable disease (15.6%), leading to an overall response rate of 94.5%. Progression was registered only in 11 cases (5.5%). The overall response rate in each arm ranged from 88.6% to 96.4%. The overall two-year local control, distant metastasis free survival, disease free survival, and overall survival were 81.7%, 33.0%, 25.4%, and 78.7% respectively. CONCLUSION: In conclusion, the planned doses of 34 Gy, 32 Gy, 24 Gy, and 24 Gy were successfully administered as single-fractions for the treatment of lung, liver, bone, and other extracranial lesions, respectively, in a prospective SRS dose-escalation trial. No dose-limiting toxicities were registered, and minimal acute and late toxicity were reported. New indications for SRS are currently being studied in oligoprogressive patients receiving targeted drugs or in combination with immunotherapy. The DESTROY-2 trial represents, in our opinion, a credible starting point for future modern radiosurgery trials.

Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study.

BACKGROUND AND OBJECTIVE: Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions. METHODS: A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes. KEY FINDINGS AND LIMITATIONS: A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p < 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a "day-case" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue. PATIENT SUMMARY: We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were willing to accept additional treatments for survival benefits, in particular treatments that preserved urinary function and reduced fatigue.

The Impact of Local Control on Overall Survival after Y-90 Selective Internal Radiotherapy of Liver Metastases in Oligometastatic Cancer: A Retrospective Analysis.

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer.

(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan-Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar's test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions.

Local treatment benefits patients with oligometastatic prostate cancer: A systematic review and meta-analysis.

OBJECTIVES: This study aims to evaluate the efficacy of local treatment (LT), including radiotherapy (RT) and cytoreductive prostatectomy (CRP), in improving outcomes for patients with oligometastatic prostate cancer (OmPCa). METHODS: A systematic review and meta-analysis of articles from PubMed, Embase, and Web of Science published between 2010 and November 2023 were conducted. The study included 11 articles, comprising three randomized controlled trials (RCTs) and eight retrospective analyses. The study assessed overall survival (OS), radiographic progression-free survival (rPFS), prostate-specific antigen (PSA) PFS, cancer-specific survival (CSS), and complication rate (CR). RESULTS: OS was significantly improved in the LT group, with both RCTs and non-RCTs showing statistical significance [hazard ratios (HR) = 0.64; 95% confidence intervals (95% CIs), 0.51-0.80; p < 0.0001; HR = 0.55; 95% CIs, 0.40-0.77; p = 0.0004]. For rPFS, RCTs did not show statistically significant outcomes (HR = 0.60; 95% CIs, 0.34-1.07; p = 0.09), whereas non-RCTs demonstrated significant results (HR = 0.42; 95% CIs, 0.24-0.72; p = 0.002). Both RCTs and non-RCTs showed a significant improvement in PSA-PFS (HR = 0.44; 95%CI, 0.29-0.67; p = 0.0001; HR = 0.51; 95% CIs, 0.32-0.81; p = 0.004). For CSS, RCTs demonstrated statistical differences (HR = 0.65; 95% CIs, 0.47-0.90; p = 0.009), whereas non-RCTs did not (HR = 0.61; 95% CIs, 0.29-1.27; p = 0.19). Regarding CR, the risk difference was -0.22 (95% CIs, -0.32 to -0.12; p < 0.00001). CONCLUSION: LT significantly improved OS and PFS in patients with OmPCa. Further RCTs are necessary to confirm these results.

A case of complete pathological response after comprehensive treatment in a patient with pulmonary adenocarcinoma with synchronous solitary brain metastasis.

Systemic chemotherapy is the standard treatment for non-small cell lung cancer with distant metastases. However, additional local treatment for brain and thoracic lesions is recommended for patients with synchronous solitary brain metastases (SSBM). We report the case of a 71-year-old male diagnosed with pulmonary adenocarcinoma and SSBM. Pathological examination of the brain metastasis showed positive immunostaining for programmed cell death ligand 1 expression. After four cycles of chemotherapy with immune checkpoint inhibitors, right upper lobectomy with ND2a-1 was performed. Pathological examination revealed complete pathological response, and this patient is expected to experience long-term survival.

Current Treatment Paradigms and Clinical Outcomes in Oligometastatic Prostate Cancer Patients: A Targeted Literature Review.

CONTEXT: Prostate cancer is the most common noncutaneous malignancy among men in the USA and Europe. There is no consensus definition of oligometastatic prostate cancer (omPC), which is often considered in two subgroups, synchronous (de novo) and metachronous (oligorecurrent), and may include patients with a low metastatic disease burden. OBJECTIVE: To summarize the epidemiology, disease definitions, mortality/survival outcomes, and treatment characteristics in both clinical trial and real-world settings among patients with synchronous, metachronous, and mixed-subtype (ie, synchronous and metachronous or undefined type) omPC, as well as low burden disease states. EVIDENCE ACQUISITION: We searched MEDLINE and Embase to identify publications reporting on epidemiology, disease definitions, clinical outcomes, and treatment characteristics of omPC. Gray literature sources (eg, ClinicalTrials.gov) were searched for ongoing trials. EVIDENCE SYNTHESIS: We identified 105 publications. Disease definitions varied across publications and omPC subtypes on the number and location of lesions, type of imaging used, and type of oligometastatic disease. Most studies defined omPC as five or fewer metastatic lesions. Data on the epidemiology of omPC were limited. Mortality rates and overall survival tended to be worse among synchronous versus metachronous omPC cohorts. Progression-free survival was generally longer among synchronous than among metachronous omPC cohorts but was more similar at longer time points. A summary of ongoing clinical trials investigating a variety of local, metastasis-directed, and systemic therapies in men with omPC is also provided. CONCLUSIONS: Definitions of oligometastatic disease depend on the imaging technique used. Epidemiologic data for omPC are scarce. Survival rates differ between synchronous and metachronous cohorts, and heterogeneous treatment patterns result in varied outcomes. Ongoing clinical trials using modern imaging techniques are awaited and needed. PATIENT SUMMARY: Definitions of oligometastatic prostate cancer (omPC) vary depending on the imaging technique used. Different treatment patterns lead to different outcomes. Robust omPC epidemiologic data are lacking.

The Importance of Radiation Planning Guidelines in Spinal Stereotactic Body Radiotherapy.

Introduction: Stereotactic body radiotherapy (SBRT) is a well-established treatment for spinal metastases. Official guidelines for radiation planning were published and revised by several groups. Here, we present real-world data about the importance of adhering to those guidelines. Case Report: A 42-year-old metastatic colon cancer patient presented with oligometastatic disease to L3 vertebra and underwent SBRT treatment. Due to lack of adhering to official guidelines both in dose regiment and in volume definition, he progressed locally and required re-treatment. Conclusions: SBRT is a well-known established choice for oligometastatic spinal lesions. Thorough evaluation of imaging and adherence to clinical guidelines are crucial for achieving a high local control rate and reducing the likelihood of re-irradiation and associated complications.

Prognosis for local radical treatment in patients with esophageal squamous cell carcinoma with low-risk oligometastatic recurrence after curative resection: a retrospective cohort study.

Background: Patients with esophageal carcinoma (EC) with recurrent disease have a poor prognosis. A limited numbers of metastases, safely treatable with curative intent, diagnosed after curative esophagectomy may be defined as oligometastatic recurrence (OLR). However, the appropriate number of metastases and metastatic organs involved remains incompletely characterized. And the role of local therapy in OLR after radical esophagectomy remains unknown. Therefore, this study aimed to more accurately define low-risk OLR in patients with esophageal squamous cell carcinoma (ESCC) treated with radical resection and investigate the role of chemotherapy combined with local treatment (CCLT) in these patients. Methods: A total of 83 sequential patients with ESCC who underwent radical esophagectomy, with an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, with ability to tolerate chemotherapy (CT) and local treatment, and with newly diagnosed recurrence between January 2010 and May 2019 in our hospital were recruited. Overall survival (OS) curves after recurrence were analyzed using the Kaplan-Meier method, and a log-rank test was used to assess the OS differences. Cox proportional hazards regression analysis was performed to identify independent factors associated with 2-year OS. Regular follow-up examinations were assessed by thoracic and upper abdominal computed tomography (CT) scanning every 3 months in the first year, every 6 months over the next 2 years, and yearly thereafter. Results: Of the 83 patients with ESCC (71 males and 12 females), the median age was 56 years (range, 37-79 years). Thirty-five patients with ESCC with ≤5 metastases safely treatable with curative intent located in a single organ had a favorable OS compared to 48 patients with metastases located in 2-3 organs with or without regional recurrence and/or regional lymph node (LN) metastases. In our study, low-risk OLR was defined as the presence of ≤5 metastases safely treatable with curative intent in a single organ and was compared to patients with 2-3 organs involved. The 2-year OS of patients with low-risk OLR with liver oligometastases was significantly worse than survival in patients with lung oligometastases (0% vs. 61.1%, P=0.009). Patients with ESCC in the low-risk OLR group treated with CCLT had a better 2-year OS after recurrence than those who received CT alone (66.7% vs. 30.4%, P=0.003). The multivariable Cox regression model identified treatment method [hazard ratio (HR) 3.920, P=0.02] as an independent factor affecting OS after recurrence for low-risk OLR. Conclusions: Low-risk OLR was defined as ≤5 metastases safely treatable with curative intent in a single organ. Patients with ESCC with low-risk OLR after curative resection treated with CCLT have a favorable OS compared to those treated with CT alone. CCLT is a promising treatment option for patients with ESCC and low-risk OLR.

Case report: Isolated oligometastatic disease of the prostate from a primary lung adenocarcinoma.

Secondary prostate cancer typically occurs from direct seeding of a renal or bladder tumor. Metastasis via hematogenous spread is exceedingly rare and is typically identified incidentally at autopsy. This report describes a 72-year-old male with lung adenocarcinoma initially staged as Stage IA2 who developed oligometastatic disease of the prostate. He was initially treated with radiation therapy and was found to have a hypermetabolic focus in the prostate gland during surveillance PET/CT imaging 6 months following treatment. Subsequent biopsy revealed metastatic lung adenocarcinoma in 6/6 core samples, leading to diagnosis of oligometastatic disease of the prostate. To our knowledge, this is the first report of isolated oligometastatic disease to the prostate from a primary lung adenocarcinoma.

Stereotactic body radiation therapy is beneficial for a subgroup of patients with urothelial cancer and solitary metastatic disease: a single institution real-world experience.

BACKGROUND: Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates, and targeted therapy. Oligometastatic disease (OMD) may be an intermediate state between localized and generalized cancer. The best treatment strategy for OMD and oligoprogressive (OPD) disease is poorly studied in mUC but local stereotactic body radiation therapy (SBRT) could be an option to avoid or delay systemic treatment. The aim of this study was to assess the efficacy and feasibility of SBRT given in a real-world patient population. METHODS: All patients with mUC treated with SBRT at Karolinska University Hospital, Stockholm, Sweden between 2009 and 2022 were included in this study. Baseline clinical characteristics, treatment data, SBRT dosimetry data and treatment outcome were collected retrospectively. The study endpoints were local control rate (LCR), progression-free-survival (PFS), overall survival (OS) and feasibility of SBRT. RESULTS: In total 39 patients were treated with SBRT. The median follow-up was 25.6 months. The LCR was 82%. PFS and OS were 4.1 and 26.2 months, respectively. Treatment was well tolerated; all patients but one (treatment related pain) completed the planned SBRT. Number of metastases irradiated with SBRT was significantly associated with outcome; patients with only one irradiated lesion had more favourable PFS compared to individuals with 2 or more metastases (HR 4.12, 95% CI: 1.81-9.38, p = 0.001). A subgroup of patients (15%) achieved a sustained long-term survival benefit and never required systemic treatments after SBRT. CONCLUSIONS: SBRT was well tolerated and associated with high LCR. A subpopulation of patients with single metastatic lesion achieved long-term OS and never required subsequent systemic treatment after SBRT. Prospective randomized studies are warranted to discover treatment predictive biomarkers and to investigate the role of SBRT in oligometastatic UC.

Stereotactic Body Radiotherapy in Recurrent and Oligometastatic Head and Neck Tumours.

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs.

Genomic Determinants Associated with Modes of Progression and Patterns of Failure in Metachronous Oligometastatic Castration-sensitive Prostate Cancer.

BACKGROUND AND OBJECTIVE: Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state in the progression of metastatic disease for which patients experience better outcomes in comparison to those with higher disease burden. Despite the generally more indolent nature, there is still much heterogeneity, with some patients experiencing a more aggressive clinical course unexplained by clinical features alone. Our aim was to investigate correlation of tumor genomics with the mode of progression (MOP) and pattern of failure (POF) following first treatment (metastasis-directed and/or systemic therapy) for omCSPC. METHODS: We performed an international multi-institutional retrospective study of men treated for metachronous omCSPC who underwent tumor next-generation sequencing with at least 1 yr of follow-up after their first treatment. Descriptive MOP and POF results are reported with respect to the presence of genomic alterations in pathways of interest. MOP was defined as class I, long-term control (LTC; no radiographic progression at last follow-up), class II, oligoprogression (1-3 lesions), or class III, polyprogression (≥4 lesions). POF included the location of lesions at first failure. Genomic pathways of interest included TP53, ATM, RB1, BRCA1/2, SPOP, and WNT (APC, CTNNB1, RNF43). Genomic associations with MOP/POF were compared using χ2 tests. Exploratory analyses revealed that the COSMIC mutational signature and differential gene expression were also correlated with MOP/POF. Overall survival (OS) was calculated via the Kaplan-Meier method from the time of first failure. KEY FINDINGS AND CLINICAL IMPLICATIONS: We included 267 patients in our analysis; the majority had either one (47%) or two (30%) metastatic lesions at oligometastasis. The 3-yr OS rate was significantly associated with MOP (71% for polyprogression vs 91% for oligoprogression; p = 0.005). TP53 mutation was associated with a significantly lower LTC rate (27.6% vs 42.3%; p = 0.04) and RB1 mutation was associated with a high rate of polyprogression (50% vs 19.9%; p = 0.022). Regarding POF, bone failure was significantly more common with tumors harboring TP53 mutations (44.8% vs25.9%; p = 0.005) and less common with SPOP mutations (7.1% vs 31.4%; p = 0.007). Visceral failure was more common with tumors harboring either WNT pathway mutations (17.2% vs 6.8%, p = 0.05) or SPOP mutations (17.9% vs 6.3%; p = 0.04). Finally, visceral and bone failures were associated with distinct gene-expression profiles. CONCLUSIONS AND CLINICAL IMPLICATIONS: Tumor genomics provides novel insight into MOP and POF following treatment for metachronous omCSPC. Patients with TP53 and RB1 mutations have a higher likelihood of progression, and TP53, SPOP, and WNT pathway mutations may have a role in metastatic organotropism. PATIENT SUMMARY: We evaluated cancer progression after a first treatment for metastatic prostate cancer with up to five metastases. We found that mutations in certain genes were associated with the location and extent of further metastasis in these patients.

Current trends in the management of Gastro-oEsophageal cancers: Updates to the ESSO core curriculum (ESSO-ETC-UGI-WG initiative).

Gastro-oEsophageal Cancers (GECs) are severe diseases whose management is rapidly evolving. The European Society of Surgical Oncology (ESSO) is committed to the generation and spread of knowledge, and promotes the multidisciplinary management of cancer patients through its core curriculum. The present work discusses the approach to GECs, including the management of oligometastatic oesophagogastric cancers (OMEC), the diagnosis and management of peritoneal metastases from gastric cancer (GC), the management of Siewert Type II tumors, the importance of mesogastric excision, the role of robotic surgery, textbook outcomes, organ preserving options, the use of molecular markers and immune check-point inhibitors in the management of patients with GECs, as well as the improvement of current clinical practice guidelines for the management of patients with GECs. The aim of the present review is to provide a concise overview of the state-of-the-art on the management of patients with GECs and, at the same time, to share the latest advancements in the field and to foster the debate between surgical oncologists treating GECs worldwide. We are sure that our work will, at the same time, give an update to the advanced surgical oncologists and help the training surgical oncologists to settle down the foundations for their future practice.

Brief Report: Long-Term Follow-Up of Adjuvant Pembrolizumab After Locally Ablative Therapy for Oligometastatic NSCLC.

Introduction: Patients with oligometastatic NSCLC benefit from locally ablative therapies (LAT); the role of adjuvant systemic therapies, however, remains less clear. In a single-arm, phase II clinical trial, we found that patients with oligometastatic NSCLC treated with a year of pembrolizumab after LAT had superior progression-free survival (PFS) compared with a historical control cohort. Herein, we present long-term follow-up on PFS and overall survival (OS). Methods: From February 1, 2015, to September 30, 2017, 45 patients with synchronous or metachronous oligometastatic (≤4 metastatic sites) NSCLC treated with LAT to all sites received adjuvant pembrolizumab every 21 days for up to 16 cycles. The primary efficacy end point was PFS from the start of pembrolizumab. Secondary end points included OS and safety. Median duration of follow-up was 66 months, and data cutoff was December 1, 2022. Results: A total of 45 patients were enrolled and treated with pembrolizumab after LAT (median age, 64 y [range, 46-82]; 21 women [47%]; 31 with a solitary oligometastatic site [69%]). At the data cutoff, 32 patients had progressive disease, 19 patients had died, and 13 patients had no evidence of relapse. Median PFS was 19.7 months (95% confidence interval: 7.6-31.7 mo); median OS was not reached (95% confidence interval: 37.7 mo-not reached). OS at 5 years was 60.0% (SE, 7.4%). Metachronous oligometastatic disease was associated with improved OS and PFS through Cox proportional hazard models. Conclusions: Pembrolizumab after LAT for oligometastatic NSCLC results in promising PFS and OS with a tolerable safety profile.

Genetic profiles of oligometastatic non-small-cell lung cancer and corresponding brain metastases.

OBJECTIVES: In patients with oligometastatic non-small-cell lung cancer (NSCLC), systemic therapy in combination with local ablative treatment of the primary tumour and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary NSCLC and corresponding brain metastases (BM). METHODS: We retrospectively identified patients with oligometastatic NSCLC and synchronous (<3 months) or metachronous (>3 months) BM who underwent surgical resection of both primary tumour and BM. Mutation profiling of formalin-fixed paraffin-embedded tumour cell blocks was performed by targeted next-generation sequencing using the Oncomine Focus Assay panel. RESULTS: Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumours (67.4%) and 40 BM (86.9%). The alteration of the primary tumours was preserved in the corresponding BM in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumours and BM was a KRAS (Kirsten rat sarcoma viral oncogene) mutation (s = 21). In 16 patients (34.8%), the BM harboured additional oncogenic alterations. The presence of a private genetic alteration in the BM was an independent predictor of shorter overall survival. CONCLUSIONS: In oligometastatic NSCLC, BM retain the main genetic alterations of the primary tumours. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the BM are dismal.

Robotic Stereotactic Body Radiation Therapy for Oligometastatic Liver Metastases: A Systematic Review of the Literature and Evidence Quality Assessment.

INTRODUCTION: The role of stereotactic body radiation therapy (SBRT) as a locally effective therapeutic approach for liver oligometastases from tumors of various origin is well established. We investigated the role of robotic SBRT (rSBRT) treatment on oligometastatic patients with liver lesions. MATERIAL AND METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The PubMed and Scopus databases were accessed by two independent investigators concerning robotic rSBRT for liver metastases, up to 3 October 2023. RESULTS: In total, 15 studies, including 646 patients with 847 lesions that underwent rSBRT, were included in our systematic review. Complete response (CR) after rSBRT was achieved in 40.5% (95% CI, 36.66-44.46%), partial response (PR) in 19.01% (95% CI, 16.07-22.33%), whereas stable disease (SD) was recorded in 14.38% (95% CI, 11.8-17.41%) and progressive disease (PD) in 13.22% (95% CI, 10.74-16.17%) of patients. Progression-free survival (PFS) rates at 12 and 24 months were estimated at 61.49% (95% CI, 57.01-65.78%) and 32.55% (95% CI, 28.47-36.92%), respectively, while the overall survival (OS) rates at 12 and 24 months were estimated at 58.59% (95% CI, 53.67-63.33%) and 44.19% (95% CI, 39.38-49.12%), respectively. Grade 1 toxicity was reported in 13.81% (95% CI, 11.01-17.18%), Grade 2 toxicity in 5.57% (95% CI, 3.82-8.01%), and Grade 3 toxicity in 2.27% (955 CI, 1.22-4.07%) of included patients. CONCLUSIONS: rSBRT represents a promising method achieving local control with minimal toxicity in a significant proportion of patients. Further studies are needed to evaluate the role of rSBRT in the management of metastatic liver lesions.

An isolated vaginal metastasis from rectal cancer: a case report.

INTRODUCTION: Vaginal metastasis from colorectal cancer is a rare occurrence, typically associated with other metastatic lesions. Isolated metastasis is exceedingly uncommon, with only a few cases documented in the literature. Vaginal involvement in colorectal cancer primarily results from direct contiguous spread from the primary tumor. CASE PRESENTATION: We present the case of a 70-year-old African woman diagnosed with adenocarcinoma of the middle rectum. She underwent chemotherapy, radiotherapy, and subsequent anterior resection. After 2 months, an isolated metastasis of rectal cancer was identified in the lower third of the left vaginal wall, confirmed by biopsy. Colonoscopy ruled out colorectal recurrence. Thoraco-abdominal computed tomography scan showed no distant metastases. The patient underwent abdominoperineal resection, removing the lateral and posterior vaginal wall with free macroscopic margins and a definitive colostomy. The final histopathological analysis confirmed the diagnosis of moderately differentiated adenocarcinoma of the vagina, measuring 5 × 4.5 cm. The rectal wall was extrinsically invaded by the tumor down to the muscularis propria while respecting the rectal mucosa. Resection margins were negative. The patient was discharged 1 week postoperation with no complications. Adjuvant chemotherapy was indicated, and the patient is currently tolerating the treatment well. CONCLUSION: Vaginal metastases from colorectal cancer are extremely rare. A vigilant gynecological examination is recommended during the follow-up of colorectal cancer patients. Diagnosis can be challenging, especially if the metastatic lesion is small and asymptomatic, even after standard radiological examination. Surgical resection followed by chemotherapy is a valid option for patients with early isolated metastases.