Metastasis-directed Radiotherapy Research Articles

Outcomes of De Novo Oligometastatic Breast Cancer Treated With Surgery of Primary and Metastasis Directed Radiotherapy.

With sensitive imaging for breast cancer, the question arises whether present-day oncologists treat dOMBC with palliative systemic therapy (ST), which, a few years earlier, would have been treated with curative intent. We retrospectively analyzed outcomes of dOMBC treated with curative intent using a combination of surgery, metastasis-directed radiotherapy (RT), and adjuvant/neoadjuvant ST and have also explored the possible role of total lesional glycolysis of metastases and p53 immunohistochemistry in predicting outcomes. Data were collected from a prospectively maintained database using electronic medical records and Radiation Oncology Information System. In the study, dOMBC was defined as up to 3 metastatic sites, all amenable to treatment with ablative RT and primary and axillary disease amenable to curative surgery. Patients were treated with surgery, ST, and RT. Patients underwent either breast conservation surgery or modified radical mastectomy. Patients were treated with 6 to 8 cycles of chemotherapy in the neoadjuvant and/or adjuvant setting. Hormone receptor-positive patients received either tamoxifen or aromatase inhibitors. Trastuzumab was offered to Her-2-neu receptor-positive patients. RT included locoregional RT and metastases-directed ablative body RT. The median progression-free survival was 39 months (95% CI: -28.7 to 50.1mo). Two and 3 year estimated disease-free survival (DFS) was 79% and 60.5%, respectively. The median overall survival was not reached. The estimated 3-year overall survival was 87.3%. Total lesional glycolysis of metastases score and p53 status did not affect DFS. Combination treatment of surgery, metastases-directed ablative RT, and ST may provide prolonged DFS in dOMBC.

Prostate-specific membrane antigen PET/CT-guided, metastasis-directed radiotherapy for oligometastatic castration-resistant prostate cancer.

e17057 Background: Systemic treatments for metastatic castration-resistant prostate cancer (mCRPC) include androgen deprivation therapy (ADT), androgen receptor pathway inhibitors (ARPIs), chemotherapy, and radiopharmaceutical therapy, all of which have associated toxicity. We hypothesized that prostate-specific membrane antigen (PSMA) PET/CT-guided, metastasis-directed radiotherapy may offer durable disease control with low toxicity rates in patients with mCRPC who have a limited number of metastatic sites. Methods: We retrospectively screened 7 prospective databases of PSMA PET/CT scans conducted between 1/2016-2/2023 for patients with mCRPC who had ≤5 sites of oligorecurrent or oligoprogressive disease and received metastasis-directed radiotherapy to all sites of disease. Castration resistance was defined as either radiographic progression or biochemical progression (two consecutive prostate-specific antigen [PSA] increases ≥3 weeks apart) while on ADT with serum testosterone <50 ng/dL. Progression-free survival (PFS), freedom from new lines of systemic therapy, and overall survival (OS) were calculated from the start of metastasis-directed radiotherapy using Kaplan-Meier analysis. Progression was defined as the first instance of biochemical progression (PSA increase of 25% and 2 ng/mL above nadir, confirmed by repeat measurement ≥3 weeks later), radiographic progression, biopsy-proven recurrence, new systemic or local therapy, or death. Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE), Version 5. Results: Twenty-six patients met inclusion criteria with a median follow-up of 34.6 months (interquartile range, 28.1-47.2 months). All patients previously received ADT, 20 (77%) received ARPIs, and 3 (12%) had prior chemotherapy. Median PSA was 1.2 ng/mL, median time from initial diagnosis was 6.2 years, and median time from castration resistance was 1.8 years. Between 10/2017-4/2023, 12 patients (46.2%) had one treated metastatic site, 11 patients (42.3%) had two, and 3 patients (11.5%) had three. Twenty-four patients (92.3%) received concurrent systemic therapy. Median PFS was 16.4 months (95% confidence interval [CI], 11.4-21.4 months). Four-year PFS was 26.7% (95% CI, 8.9-44.5%). Median time to initiation of a new line of systemic therapy was 18.0 months (95% CI, 0-36.2 months). Four-year freedom from new lines of systemic therapy was 36.1% (95% CI, 15.5-56.7%). Median OS was not reached. Four-year OS was 72.5% (95% CI, 51.1-93.9%). Grade 2 and ≥3 toxicity rates were 3.8% and 0%, respectively. Conclusions: For patients with oligometastatic CRPC, PSMA PET/CT-guided metastasis-directed radiotherapy appears to offer durable disease control with low toxicity. Further prospective studies are needed to compare PSMA PET/CT-guided versus conventional imaging-guided radiotherapy.

Concomitant Immunotherapy and Metastasis-Directed Radiotherapy in Upper Tract Urothelial Carcinoma: A Biomarker-Driven, Original, Case-Based Proof-of-Concept Study.

Metastatic upper tract urothelial carcinoma (mUTUC) has a poor prognosis. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in patients with metastatic urothelial carcinoma. However, data supporting the use of ICIs in patients with mUTUC are limited. A promising synergy between ICI and concomitant radiotherapy (RT) has been reported in patients with mUTUC. Our research involved a case-based investigation and emphasized the successful integration of different specialists' skills. Observed after partial urethrectomy procedures for muscle-invasive upper tract urothelial carcinoma (UTUC), the radiological detection of lung metastases prompted us to implement cisplatin-based first-line chemotherapy and molecular characterization in the treatment process. We uncovered alterations in the ERBB2 and FGFR3 genes and mismatch repair deficiency at a molecular level. First-line chemotherapy treatment led to a stable disease, and the patient was started on maintenance immunotherapy with Avelumab. Subsequently, an increase in the size of the lung nodules was described, and the patient received radiotherapy for three lung lesions in combination with immunotherapy. After 3 months, a restaging CT scan reported a complete response, which is still ongoing. We discuss the mechanisms driving RT/ICI synergy and the molecular profile of mUTUC as factors that should be considered in therapeutic strategy planning. Molecular insight enhances the originality of our study, providing a nuanced understanding of the genetic landscape of mUTUC and paving the way for targeted therapeutic strategies. The therapeutic armamentarium expansion encourages the design of a multimodal and personalized approach for each mUTUC patient, taking into account tumor heterogeneity and molecular profiling.

Utility of PSMA PET Guided Metastasis-Directed Radiotherapy

Metastasis-directed radiotherapy (MDT) is becoming a mainstay in the management of oligometastatic prostate cancer (PCa), and PSMA-PET is currently the most sensitive imaging modality for PCa metastasis screening. The efficacy of MDT guided by PSMA-PET imaging has not yet been well characterized. Moreover, the optimal role of androgen deprivation therapy (ADT) in the context of MDT is not known. We sought to assess the efficacy of PSMA PET-guided MDT in patients with metastatic PCa treated with and without ADT. This is a single institutional retrospective study of patients diagnosed with metastatic prostate cancer by PSMA-PET imaging who were treated with MDT. Biochemical progression was defined as a PSA increase of ≥ 25% and ≥ 2 ng/mL if PSA was ≥ 2 ng/mL at time of initiating salvage treatment, or a PSA increase of ≥ 25% if PSA was < 2 ng/mL at time of salvage treatment. Survival analyses were performed using the Kaplan-Meier method with log-rank testing for significance. Cumulative incidence analyses were performed with Gray's testing for significance. Adverse event data were assessed per CTCAE v5 guidelines. A total of 196 PSMA PET-avid lesions from 101 patients were irradiated with stereotactic body radiotherapy (SBRT). Median time from prior definitive locoregional therapy to MDT was 6.2 years. 79 patients had hormone-sensitive PCa (HSPC) and 22 patients had castration-resistant PCa (CRPC) at time of MDT. 47 of 79 (59%) patients with HSPC received ADT along with MDT, and 20 of the 47 patients received augmented ADT. 25 of the 32 (78%) HSPC patients receiving MDT without ADT had undergone at least one prior course of ADT, and none had castrate levels of testosterone at time of MDT with a median testosterone level of 341 ng/dl. With a median follow-up of 22.4 months, 5 of 196 lesions (2.6%) demonstrated radiographic progression. 2-year cumulative incidence of progression from HSPC to CRPC was 11% in patients who received ADT at time of MDT and 35% in those who did not (P = 0.027). Median biochemical progression free survival of patients with CRPC, HSPC treated without ADT, and HSPC treated with ADT following MDT was 5.4, 7.6, and 43.9 months respectively (P<0.0001). 2-year overall survival of the abovementioned groups was 72.2%, 100%, and 97.5% respectively (P<0.001). No Grade 3-5 adverse effects were observed. MDT guided by PSMA-PET imaging is well-tolerated and delays biochemical progression in patients with CRPC and HSPC, with a greater effect observed in patients also receiving ADT.

The Role of Local Prostate and Metastasis-Directed Radiotherapy in the Treatment of Oligometastatic Prostate Cancer

The local ablative therapy for oligometastatic disease (OMD) has the potential to delay further metastases and improve survival. However, it has not been fully elucidated how prostate primary radiotherapy (PPR) and metastasis-directed radiotherapy (MDR) affect prognosis in each different OMD scenario. Herein, we tried to provide efficacy and future perspectives for MDR in oligometastatic prostate cancer. Patients diagnosed with prostate cancer between 2010 and 2019 and treated for OMD (≤5 active lesions), which occurred synchronously or metachronously, were included. All patients received MDR at all detected lesions (OMDRT). OMDRT which was performed as soon as OMD was detected was classified as early, and OMDRT for progressions after hormone therapy was classified as late. The primary endpoint was survival after OMDRT, and timing of progression after RT was also analyzed. A total of 82 patients with oligometastatic prostate cancer received OMDRT. Among 36 patients with synchronous OMD, 58% received PPR at diagnosis, and 64% received early OMDRT. Among 46 patients with metachronous OMD, 80% received early OMDRT, and 28 received sequential OMDRT for repetitive OMD events. With a median follow-up of 32 months after OMDRT, 54 patients experienced progression and 5-year survival was 78%. Survival was highest in patients with synchronous OMD and early RT (5-year 86%), and 5-year survival of patients with metachronous OMD and early RT was significantly higher than those with late RT (78% vs. 44%, p = 0.003). Survival of patients with synchronous OMD and PPR was significantly higher than those without PPR or with metachronous OMD (5-year 90% vs. 66%, p = 0.030), by delaying progressions (17.9 vs. 7.0 months, p = 0.005). Survival gain could be achieved through OMDRT in oligometastatic prostate cancer, especially in synchronous OMD status. Also, it was possible to improve the prognosis further when OMDRT was performed early and with PPR.

Survival Outcomes for Oligometastatic vs. Polymetastatic Extensive-Stage Small Cell Lung Cancer Following Consolidative Thoracic Radiotherapy

For patients with limited metastatic burden, metastasis-directed radiotherapy has been shown to be associated with improved OS for certain types of cancer. However, these prior trials did not include patients with ES-SCLC. It is not yet clear if patients with oligometastatic ES-SCLC have improved outcomes over polymetastatic ES-SCLC after cTRT. We identified patients treated with cTRT for ES-SCLC in 2013-2020 at a single institution. Oligometastatic disease was defined at the time of diagnosis as three or fewer organs with distant disease, and with each organ having three or fewer metastatic lesions. All other patients were considered polymetastatic. The Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazards regression were used to compare OS, progression-free survival (PFS), local recurrence-free survival (LRFS), and new metastasis-free survival (NMFS) between oligometastatic and polymetastatic ES-SCLC patients undergoing cTRT. Among 70 included patients, 36 were defined as oligometastatic. All patients received platinum-doublet chemotherapy and cT. Immunotherapy was given in 7 (19.4%) oligometastatic patients and 5 (14.7%) polymetastatic patients (p = 0.56). Median follow-up time was 38.2 months. Multivariable Cox regression analysis showed that oligometastatic disease (vs. polymetastatic disease) at diagnosis was associated with improved OS (hazard ratio [HR] 0.44, 95% CI 0.25-0.78, p = 0.005, 1-year OS 86.1% vs. 46.9%, 2-year OS 47.1% vs. 15.1%). PFS, LRFS, and NMFS were not significantly different between the cohorts. Among oligometastatic patients, pleural involvement (HR 2.44, 95% CI 1.02-5.83, p = 0.046) and lung involvement (HR 4.93, 95% CI 1.02-23.9, p = 0.047) were associated with inferior OS. Among the 26 of 36 (72.2%) oligometastatic patients with neither pleural nor bilateral lung involvement, 1-year OS was 88.5% and 2-year OS was 58.3%. We observed that oligometastatic ES-SCLC patients treated with cTRT (especially those without pleural or bilateral lung involvement) have superior OS than those with polymetastatic disease. We encourage enrollment on the NRG LU007/RAPTOR randomized trial to determine the impact of complete or incomplete consolidative RT to up to 5 sites in ES-SCLC, especially in those with oligometastatic disease.

Independent Validation of a Unifying Prognostic Model for Intracranial and Extracranial Metastasis-directed Radiotherapy.

The aim of this study was to analyze the validity of a unifying prognostic model, originally developed by Kowalchuk et al., because relevant variations in clinical practice and observed survival may impact on the performance of predictive tools. Retrospectively, data from a single institution were analyzed. The study included 253 patients managed with radiotherapy for spine and/or brain metastases. The Kowalchuk et al. score [3 parameters including performance status, number of organ systems involved with disease outside of the organ system of the treatment target, and treatment of intracranial target(s)] was assigned and the resulting prognostic strata compared. The decision tool developed by Kowalchuk et al. performed well, e.g., in terms of 2-year survival. Complementary information could be obtained by analyses of blood test results such as hemoglobin, albumin, and C-reactive protein. The new unifying score emerged as a valid prognostic model in our external validation database.

Development and validation of a unifying pre-treatment decision tool for intracranial and extracranial metastasis-directed radiotherapy.

Though metastasis-directed therapy (MDT) has the potential to improve overall survival (OS), appropriate patient selection remains challenging. We aimed to develop a model predictive of OS to refine patient selection for clinical trials and MDT. We assembled a multi-institutional cohort of patients treated with MDT (stereotactic body radiation therapy, radiosurgery, and whole brain radiation therapy). Candidate variables for recursive partitioning analysis were selected per prior studies: ECOG performance status, time from primary diagnosis, number of additional non-target organ systems involved (NOS), and intracranial metastases. A database of 1,362 patients was assembled with 424 intracranial, 352 lung, and 607 spinal treatments (n=1,383). Treatments were split into training (TC) (70%, n=968) and internal validation (IVC) (30%, n=415) cohorts. The TC had median ECOG of 0 (interquartile range [IQR]: 0-1), NOS of 1 (IQR: 0-1), and OS of 18 months (IQR: 7-35). The resulting model components and weights were: ECOG = 0, 1, and > 1 (0, 1, and 2); 0, 1, and > 1 NOS (0, 1, and 2); and intracranial target (2), with lower scores indicating more favorable OS. The model demonstrated high concordance in the TC (0.72) and IVC (0.72). The score also demonstrated high concordance for each target site (spine, brain, and lung). This pre-treatment decision tool represents a unifying model for both intracranial and extracranial disease and identifies patients with the longest survival after MDT who may benefit most from aggressive local therapy. Carefully selected patients may benefit from MDT even in the presence of intracranial disease, and this model may help guide patient selection for MDT.

Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy.

Ablative radiotherapy is a highly efficient treatment modality for patients with metastatic prostate cancer (PCa). However, a subset of patients does not respond. Currently, this subgroup with bad prognosis cannot be identified before disease progression. We hypothesize that markers indicative of radioresistance, stemness and/or bone tropism may have a prognostic potential to identify patients profiting from metastases-directed radiotherapy. Therefore, circulating tumor cells (CTCs) were analyzed in patients with metastatic PCa (n=24) during radiotherapy with CellSearch, multicolor flow cytometry and imaging cytometry. Analysis of copy-number alteration indicates a polyclonal CTC population that changes after radiotherapy. CTCs were found in 8 out of 24 patients (33.3%) and were associated with a shorter time to biochemical progression after radiotherapy. Whereas the total CTC count dropped after radiotherapy, a chemokine receptor CXCR4-expressing subpopulation representing 28.6% of the total CTC population remained stable up to 3 months. At once, we observed higher chemokine CCL2 plasma concentrations and proinflammatory monocytes. Additional functional analyses demonstrated key roles of CXCR4 and CCL2 for cellular radiosensitivity, tumorigenicity and stem-like potential in vitro and in vivo. Moreover, a high CXCR4 and CCL2 expression was found in bone metastasis biopsies of PCa patients. In summary, panCK+ CXCR4+ CTCs may have a prognostic potential in patients with metastatic PCa treated with metastasis-directed radiotherapy.

A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL)

BackgroundThe significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases.MethodsThis phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI.DiscussionThis will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone.Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358

18F-DCFPyL (PSMA) PET as a radiotherapy response assessment tool in metastatic prostate cancer.

Prostate Specific Membrane Antigen (PSMA) - positron emission tomography (PET) guides metastasis-directed radiotherapy (MDRT) in prostate cancer (PrCa). However, its value as a treatment response assessment tool after MDRT remains unclear. Importantly, there is limited understanding of the potential of radiotherapy (RT) to alter PSMA gene (folate hydrolase 1; FOLH1) expression. We reviewed a series of 11 men with oligo-metastatic PrCa (25 metastasis sites) treated with MDRT before re-staging with 18F-DCFPyL (PSMA) PET upon secondary recurrence. Acute effects of RT on PSMA protein and mRNA levels were examined with qPCR and immunoblotting in human wild-type androgen-sensitive (LNCap), castrate-resistant (22RV1) and castrate-resistant neuroendocrine (PC3 and DU145) PrCa cell lines. Xenograft tumors were analyzed with immunohistochemistry. Further, we examined PSMA expression in untreated and irradiated radio-resistant (RR) 22RV1 (22RV1-RR) and DU145 (DU145-RR) cells and xenografts selected for survival after high-dose RT. The majority of MDRT-treated lesions showed lack of PSMA-PET/CT avidity, suggesting treatment response even after low biological effective dose (BED) MDRT. We observed similar high degree of heterogeneity of PSMA expression in both human specimens and in xenograft tumors. PSMA was highly expressed in LNCap and 22RV1 cells and tumors but not in the neuroendocrine PC3 and DU145 models. Single fraction RT caused detectable reduction in PSMA protein but not in mRNA levels in LNCap cells and did not significantly alter PSMA protein or mRNA levels in tissue culture or xenografts of the other cell lines. However, radio-resistant 22RV1-RR cells and tumors demonstrated marked decrease of PSMA transcript and protein expression over their parental counterparts. PSMA-PET may be a promising tool to assess RT response in oligo-metastatic PrCa. However, future systematic investigation of this concept should recognize the high degree of heterogeneity of PSMA expression within prostate tumors and the risk for loss of PSMA expression in tumor surviving curative courses of RT.

The oncological characteristics of non-prostate-specific membrane antigen (PSMA)-expressing primary prostate cancer on preoperative PSMA positron emission tomography/computed tomography.

The oncological characteristics of non-prostate-specific membrane antigen (PSMA)-expressing primary prostate cancer on preoperative PSMA positron emission tomography/computed tomography.

Outcome of Cyto Reductive Prostatectomy and ADT and Metastasis-Directed Therapy (MDT) in Patients with Oligometastatic Prostate Cancer: A Prospective Cohort

Objective: We wanted to evaluate the efficacy and safety of a new treatment of Oligosmetastatic prostate cancer (OMPC) with multimodal approach including local primary tumor therapy, in the form of Cytoreductive Prostatectomy, metastasis-directed therapy (MDT), and hormonal therapy . Methods: We reviewed data of patients with Oligometastatic Prostate Cancer(OMPC) at diagnosis treated in our institutions with ADT and followed by Cytoreductive Prostatectomy (CP) with or without metastases-directed radiotherapy. In this prospective cohort study, 19 patients underwent Cytoreductive radical Prostatectomy and routine Lymphadenectomy, ADT with Degarelix, Aberateron and Prednisolone in the form of neoadjuvant setting during the period of Jan 2016 - March 2021. Of these,05 patients (26.31%) received stereotactic body radiation therapy (SBRT) to all metastatic sites as a MDT in addition to above protocol. Results: The median follow-up period was 46.2 months. Perioperative outcomes, clinical progression, and cancer-specific mortality (CSM) were evaluated. Median age was 72 yr. Median operative time, blood loss, and length of hospitalization were 176 min, 850 ml, and 6 d, respectively. Overall, two patients (10.52%) experienced grade 3 complications in the postoperative period. All received blood transfusions. Overall, 15 (78.94%) and 8 (42.10%) patients had lymph node invasion and positive surgical margins, respectively. Adjuvant Radiation Therapy and androgen deprivation therapy was administered to all 8 patients (42.10%)who confirmed margin Positive status. Of the 19 patients, the 3-year castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival was100%. Our findings support the safety and effectiveness of Cytoreductive Prostatectomy (C P) in a highly selected cohort of PCa patients with bone metastases and long-term follow-up Conclusion: This Prospective cohort revealed the feasibility of combining ADT and Cytoreductive prostatectomy and metastasis-directed radiotherapy for newly-diagnosed Oligometastatic Prostatic Cancer. This treatment strategy has the potential to delay the progression to CRPC. Bangladesh J. Urol. 2021; 24(2): 146-154

1264MO Development and validation of a unifying pre-treatment decision tool for intracranial and extracranial metastasis-directed radiotherapy

Metastasis-directed therapy (MDT) has the potential to improve clinical outcomes and even overall survival (OS). However, prognostication and appropriate patient selection for MDT remain challenging. We aimed to develop a unifying model predictive of OS for patients with intracranial and extracranial disease to refine patient selection for MDT and clinical trials.

Androgen Deprivation therapy for Oligo-recurrent Prostate cancer in addition to radioTherapy (ADOPT): study protocol for a randomised phase III trial

BackgroundMore than 60% of oligo-recurrent prostate cancer (PCa) patients treated with metastasis-directed radiotherapy (MDRT) develop biochemical recurrence within 2 years. This recurrence rate emphasises the need for improved treatment and patient selection. In line with the treatment of primary PCa, the efficacy of MDRT may be enhanced when combined with androgen-deprivation therapy (ADT). Furthermore, the availability of PSMA PET/CT offers an excellent tool for optimal patient selection for MDRT. This phase III randomised controlled trial will investigate the role of the addition of ADT to MDRT in oligo-recurrent PCa patients selected with PSMA PET/CT to enhance oncological outcome.MethodsTwo hundred and eighty patients will be randomised in a 1:1 ratio to the standard treatment arm (MDRT alone) or the experimental arm (MDRT + 6 months ADT). Patients with biochemical recurrence after primary treatment of PCa presenting with ≤ 4 metastases will be included. The primary endpoint is the 2.5-year metastases progression-free survival (MPFS). Secondary endpoints are acute and late toxicity, quality of life, biochemical progression-free survival, overall survival, and the sensitivity of the PSMA PET/CT for detecting oligometastases at low PSA-levels. So far, between March 2020 and December 2021, one hundred patients have been included.DiscussionThis phase III randomised controlled trial will assess the possible benefit of the addition of 6 months ADT to MDRT on metastases progression-free survival, toxicity, QoL and survival in PCa patients with 1–4 recurrent oligometastatic lesions.Trial registrationClinicalTrials.gov, NCT04302454. Registered 10 March 2020.

Radiotherapy in oligometastatic prostate cancer—a pattern of care survey among members of the German Society for Radiation Oncology (DEGRO)

PurposeDue to improved imaging, oligometastatic prostate cancer (OMPC) is diagnosed more frequently. Growing evidence shows that patients with a limited number of metastases benefit from primary-directed radiotherapy (PDT) as well as from metastasis-directed radiotherapy (MDT). This survey investigates the current treatment practice for OMPC among German-speaking radiation oncologists.MethodsMembers of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie [DEGRO]) were surveyed regarding their current treatment practice via an anonymous online questionnaire sent by email. The survey included six general items and 14 specific items regarding treatment characteristics. Questionnaires with at least 50% of questions completed were considered for further analysis.ResultsA total of 204 responses were received (15% response rate), 167 were considered for further analysis. Most respondents stated to be specialized in treating prostate cancer patients and to treat 10–30 patients with OMPC per annum; 97% considered PSMA-PET/CT necessary to define oligometastatic disease. Opinions differed regarding the use of systemic therapies: 63% of the respondents aimed to defer systemic therapy using radiotherapy in OMPC, whereas 37% considered systemic therapy necessary. In the setting of synchronous OMPC, 97% recommended PDT with or without a combination of MDT and/or systemic therapy. For metachronous nodal or bone oligometastatic recurrence, 98 and 99%, respectively, would opt for MDT. The majority would combine MDT with systemic therapy in patients with metachronous oligorecurrence. Respondents recommended normofractionation, hypofractionation, and SBRT for lymph node metastases in 49, 27, and 24%, respectively. No consensus existed regarding the field size for MDT of lymph node metastases. Most respondents preferred > 5 fractions for treatment of bone metastases.ConclusionLocal radiotherapy for PDT and MDT is routinely used among respondents of this survey, representing 12% of all German-speaking radiation oncologists. The timing of systemic therapy, fractionation schedules, and field sizes are handled differently and remain an area of active investigation.

Narrative review of local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer.

The role of local treatment in patients with de novo metastatic prostate cancer is controversial. In population-based retrospective studies, metastatic prostate cancer patients who received local treatment with prostate radiotherapy showed a better prognosis than those who did not. In addition, several prospective randomized studies demonstrated that prostate radiotherapy achieves a survival benefit for patients with oligo-metastasis. Moreover, the efficacy of metastasis-directed radiotherapy was evaluated, revealing a potential benefit for patients with oligo-metastasis. Importantly, these radiotherapies may reduce the occurrence of symptomatic local events. In this review, the rationale, efficacy and future perspectives for local prostate and metastasis-directed radiotherapy in the treatment of metastatic prostate cancer were described and summarized.

Combined radio-immunotherapy: An opportunity to increase the therapeutic ratio of oligometastasis-directed radiotherapy.

The utility of radiotherapy as a means of palliating symptoms due to metastatic cancer is well-accepted. A growing body of literature suggests that radiotherapy may play a role beyond palliation in some patients with low-burden metastatic disease. Recent data suggest that oligometastasis-directed radiotherapy may improve progression-free and even overall survival in select patients. Immunotherapy also has a growing role in the management of patients with metastatic cancer and, like radiotherapy, appears to be most effective in the setting of low-volume disease. Thus, the addition of immunotherapy may be a feasible means of increasing the therapeutic ratio of metastasis-directed radiotherapy, particularly among patients with oligometastatic cancer.

Abstract CS1-1: Oligometastatic disease: Definitions and practice patterns

Abstract Available evidence on oligometastatic disease (OMD) and its treatment, more in particular the use of metastasis directed radiotherapy (MDRT), mostly derives from retrospective, single-center series, with significant heterogeneity in patient inclusion criteria, definition of OMD, and outcomes reported. No molecular biomarker being clinically available for the identification of patients with true OMD, its diagnosis is typically based on imaging findings. However, the presentation on imaging may represent a whole range of different clinical scenarios, depending on the moment in the disease history, and the use - or not - of systemic therapy. Based on the available data, consensus was reached amongst radiation oncology experts representing ASTRO and ESTRO, that OMD can to date be defined as 1-5 metastatic lesions, both occurring synchronously or metachronously, in which a controlled primary tumor is considered optional but with as prerequisite that all metastatic sites must be safely treatable. Moreover, in a collaboration between the ESTRO and EORTC, subclassification into oligorecurrence, oligoprogression, and oligopersistence was suggested, depending on whether OMD is diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion is progressing on current imaging.While further evidence is being generated in (randomized) clinical trials as well as through collecting real-world data from clinical practice, it is imperative to use consistent definitions and reporting to further refine and validate the OMD classification and nomenclature, and to acquire a better understanding of the true impact of MDRT in different clinical scenarios. Citation Format: Y Lievens. Oligometastatic disease: Definitions and practice patterns [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr CS1-1.

Metastasis-Directed Radiotherapy for Oligoprogressive or Oligopersistent Metastatic Colorectal Cancer

IntroductionSome patients with cancer may present with progressive or persistent disease at a limited number of sites following a period of treatment response. We evaluated the safety and effectiveness of metastasis-directed radiotherapy (MRT) for oligoprogressive or oligopersistent disease in patients receiving systemic treatment for metastatic colorectal cancer (mCRC). Patients and methodsPatients with mCRC who received 5-fluorouracil, leucovorin, and oxaliplatin; 5-fluorouracil, leucovorin, and irinotecan; and/or capecitabine chemotherapy between 2011 and 2020 at a single institution were identified. Then, those who underwent MRT for five or fewer lesion sites while receiving systemic treatment for other metastases were categorized. The primary endpoint was time to change to systemic therapy. Secondary endpoints included MRT-related toxicity, overall survival, and local control. ResultsAmong 4157 patients included, 91 (2%) received MRT to limited lesion sites (55 oligoprogressive and 36 oligopersistent) during systemic treatment following a period of treatment response. The median time to change to next-line systemic therapy was 5 months in the overall cohort (measured from the current chemotherapy session) and 9.5 (range, 6.0–40.6) months in the MRT group (measured from the MRT session). No severe toxicity or systemic treatment interruption was observed following MRT. The 1-year local control and overall survival rates were 69% and 99%, respectively. ConclusionIn patients with oligoprogressive or oligopersistent mCRC, MRT may be performed safely in conjunction with systemic treatment to maximize the benefit of systemic therapy and to prolong the time to change to systemic therapy. Further prospective studies should confirm these findings.