Metastasis-directed Radiation Therapy Research Articles

Expert Perspectives on Controversies in Castration-Sensitive Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 1

Purpose: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC. Materials and Methods: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy. Results: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC. Conclusions: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC.

Clinical Outcomes with Stereotactic Body Radiation Therapy for Oligometastatic Prostate Cancer: Results from a Prospective Registry Trial

Metastasis-directed radiation therapy using stereotactic body radiation therapy (SBRT) in oligometastatic prostate cancer (Oligo PCa) has a demonstrated benefit for local control and biochemical recurrence free survival for men with oligorecurrent PCa; however, the impact of SBRT within other oligometastatic states and in the context of systemic therapy remains poorly characterized. In this study, we investigate prognostic factors for clinical outcomes in a prospective cohort of Oligo PCa patients treated with metastasis-directed SBRT. Using a single-institution registry trial, we analyzed a prospective cohort of 86 patients with Oligo PCa (≤5 metastatic lesions) and treated with metastasis-directed SBRT between 2017- 2022. Patients were classified as synchronous, metachronous, or induced oligometastatic disease as per the ESTRO guidelines. We evaluated the time to radiographic progression (TTRP), defined as the time from SBRT start date to radiographic progression, as well as time to initiation of new treatment (TTNT), defined as the time from SBRT end date to initiation of new therapy (systemic or radiation therapy). Time to event (TTE) was defined as the time from SBRT start date to radiographic progression or initiation of new therapy, whichever occurred first. Patients without documented events were censored at the date of last disease assessment. Comparative analyses were performed using Kaplan-Meier and Cox proportional hazards regression methods. Eighty-six men with Oligo PCa treated with SBRT were followed for a median of 16.4 months with M0 (73%), Oligo PCa (21%) or polymetastatic PCa (6%) GS > = 8 (63%) at initial diagnosis. At the time of treatment with initial SBRT, 21% had synchronous oligometastatic disease, 63% had metachronous or repeat oligorecurrence or oligoprogression, and 16% had induced oligometastatic disease. Most patients were treated to 1-3 sites (94%), which predominantly included bone (86%), and the median dose was 35 Gy/5F. Concurrent systemic therapy during SBRT was seen in 85% of patients, including (60.5% with new generation androgen receptor signaling inhibitors). Overall survival at 1-year and 2-years was 96.9% [95% CI, 88.2-99.2%] and 94.4% [95% CI, 83.2-98.2%]. Using univariable analysis, those who did not receive systemic treatment during SBRT had significantly shorter TTRP (HR 3.67, [95% CI, 1.62-8.32], p = 0.002), TTNT (HR 3.24, 95% CI [1.49-7.06], p = 0.003), and TTE (HR 3.05, [95% CI, 1.44-6.45], p = 0.004). Additionally, patients treated with SBRT for metachronous (HR 2.89, [95% CI 0.68-12.30]) and induced metastatic disease (HR 8.96, [95% CI 1.85-43.37]) had significantly shorter TTE compared to synchronous oligometastatic disease (p = 0.006). Using a prospective registry cohort of men with Oligo PCa treated with SBRT, we identify an association of oligometastatic state and the use of concurrent systemic therapy with improved TTRP and TTNT. Further prospective studies are warranted.

Savremeni pristup u lečenju oligometastatskog karcinoma prostate

Oligometastatic disease is defined as an intermediate state between localized and widespread metastatic disease. Oligometastatic prostate cancer is generally defined by the presence of five or fewer metastatic sites on imaging. In the era of precision and personalized cancer care, the introduction of more sensitive imaging technologies and the availability of safe and effective localized non-or minimally invasive treatment options, have led to an increase in the incidence and clinical interest in oligometastatic prostate cancer. In addition, the therapeutic paradigm for oligometastatic prostate cancer is evolving toward a more aggressive approach. Retrospective studies have shown that in the metastatic setting, treatments such as radical prostatectomy and local or metastasis-directed radiation therapy can be performed with minimal risk of toxicity and may enhance clinical outcomes. As there is insufficient data to draw reliable conclusions about their impact on survival, aggressive approaches in the treatment of oligometastatic prostate cancer should be considered only in the context of prospective clinical trials, with the patient informed of the limited evidence of benefit. The current inconsistent approach of detecting and treating oligometastatic prostate cancer patients will need to be standardized in order for future clinical studies to be properly performed and, more importantly, compared. These crucial conditions will reveal if oligometastasis diagnosis and therapy should be included in the standard clinical practice of prostate cancer patients.

Enhancing Radiation Therapy Plan Quality in a Multi-Site Randomized Clinical Trial with a Benchmark Credentialing Exercise: The VA STARPORT Experience

<h3>Purpose/Objective(s)</h3> VA STARPORT is a phase 2/3 trial comparing systemic therapy +/- PET-directed, metastasis directed radiation therapy (RT) for oligo recurrent prostate cancer enrolling at 16 sites. RT options include SBRT to metastases only or elective nodal RT with a simultaneous integrated boost (ENRT+SIB). We hypothesized that benchmark credentialing exercise results that were shared across study sites would enhance protocol understanding, increase compliance, and identify opportunities to improve the study protocol. <h3>Materials/Methods</h3> A hypothetical benchmark patient scenario was created including prior definitive prostate RT with recurrences in a right obturator node, right external iliac node, and right iliac bone. OARs, target structures, and prior RT dosimetry were created on an open-source CT dataset. The benchmark exercise included: Phase 1: Each site described their preferred protocol treatment approach (SBRT or ENRT+SIB) and RT details (dose, fractions, PTV margins, and method to address prior RT). Phase 2: Each site performed 2 standardized treatment planning exercises on the dataset (SBRT vs. ENRT+SIB). Compliance worksheets summarized and assessed dose metrics, target coverage, and conformality. Plan DICOM files, worksheets, and IMRT QA were submitted for central RT quality assurance (RTQA). Phase 3: SBRT and ENRT + SIB plans were scored by the study RTQA team using a numerical plan scoring system. Scorecards and lessons learned were discussed with local investigators and further communicated to all study sites. <h3>Results</h3> Site survey results (n=16) revealed 8 preferred ENRT+SIB. Only 4 ENRT+SIB prescriptions were per-protocol, and there was PTV margin non-compliance in an intended SBRT plan. Benchmark lessons learned are summarized in the Table. <h3>Conclusion</h3> A practical and useful benchmark exercise successfully assessed protocol compliance, revealed key lessons, and identified ways to improve the protocol's RT section and RTQA process. Teaching points and learned planning strategies were shared across study sites and have a potential to improve metastasis-directed RT planning for both trial and non-trial patients at each facility.

Planning Trade-offs for SABR in Patients With 4 to 10 Metastases: A Substudy of the SABR-COMET-10 Randomized Trial

The oligometastatic state refers to a clinical scenario where a cancer is no longer localized, but not yet widely metastatic. Although many trials define the oligometastatic state as 1 to 3 or 1 to 5 metastatic lesions, there is no universally accepted definition.1-4 A recently published ESTRO-ASTRO consensus article, in defining oligometastasis, states that “the possibility to safely deliver curative intent metastasis-directed radiation therapy determines the maximum number.”5 However, the maximum number of metastases that can be safely treated is unknown.

Metastasis-Directed Radiation Therapy with Consolidative Intent for Oligometastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

Simple SummaryPatients with oligometastatic urothelial carcinoma represent a challenging subset of subjects to manage. Herein we summarized evidence about the role of metastasis-directed radiation therapy in this clinical setting. Available preliminary evidence supports the role of metastasis-directed radiation therapy as a safe and efficacious option as it has the potential to facilitate local disease control and overall survival. However, in the absence of data from high-quality trials, definitive recommendations cannot be provided, and patients should be counseled on an individual basis.The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with consolidative intent in oligometastatic UC patients. A systematic review was performed in December 2021. Six studies involving 158 patients were identified. Most patients (n = 120, 90.2%) had a history of bladder cancer and the most frequent sites of metastases were lymph nodes (n= 61, 52.1%) followed by the lungs (n = 34, 29%). Overall, 144 metastases were treated with MDRT. Median follow-up ranged from 17.2 to 25 months. Local control rates ranged from 57% to 100%. Median Overall Survival (OS) ranged from 14.9 to 51.0 months and median progression-free survival ranged from 2.9 to 10.1 months. Rates of OS at one and two years ranged from 78.9% to 96% and from 26% to 63%, respectively. Treatment-related toxicity was recorded in few patients and in most cases a low-grade toxicity was evident. MDRT with consolidative intent represents a potential treatment option for selected patients with oligometastatic UC.

Oligometastases Treated With an Elective Simultaneous Integrated Boost Have Reduced Marginal Recurrence Rates

<h3>Purpose/Objective(s)</h3> Radiation is increasingly used to treat oligometastatic patients (OM). Following metastasis directed radiation therapy, progression in nearby nodal basins or bones is common. We previously reported clinical outcomes of OM treated with an elective simultaneous integrated boost (SIB) technique delivering higher doses to known metastases and reduced doses to adjacent bones/nodal basins. Here we compare outcomes of OM receiving radiation to metastases alone (MA) versus those treated via an SIB. We hypothesized that use of SIB would maintain treated metastasis control (TMC) while reducing MR. <h3>Materials/Methods</h3> OM patients with ≤5 active metastases treated with either SIB or MA at our IRB approved sites from 2013-2018 were analyzed for toxicities, pain control, and recurrence patterns. TMC was defined as absence of progression in high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside elective PTV, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as any recurrence outside of the treatment PTVs not meeting other criteria. Outcome rates were estimated using the Kaplan-Meier method. Patients treated with the two techniques were compared using the log rank test. <h3>Results</h3> 101 patients were treated to 90 SIB (58% nodal and 42% osseous) and 46 MA (22% nodal and 78% osseous) sites. The most common primary tumors were prostate (37%), lung (15%), and breast (7%). Median follow up among surviving patients was 24.6 months (range 1.4-71.0). Of the MA treated patients, doses ranged from 18 Gy in 1 fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No patients in either cohort experienced acute grade ≥3 toxicity. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis n = 1, vertebral body compression n = 2) and no MA patients. There was similar crude pain relief between cohorts: 82% with MA (9/11 patients reporting improved pain) and 86% with SIB (19/22). Crude MR were more frequent in the MA group 13% (n = 6) compared to SIB group 2% (n = 2). MR-free survival at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (<i>P</i> = 0.07). Crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences found in DR-free survival (<i>P</i> = 0.24) or Disease-free survival (<i>P</i> = 0.4) and Overall survival (<i>P</i> = 0.26) between MA and SIB cohorts. <h3>Conclusion</h3> Both SIB and MA irradiation of OM achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for OM treated with SIB. Although more late grade 3 toxicities were seen in the SIB cohort, these were mechanistically related to the high dose PTV and not the elective volume, with differences in treated metastasis location/characteristics. Further investigation of this technique with prospective trials is warranted.

PD55-05 METASTASIS-DIRECTED RADIATION THERAPY AFTER RADICAL CYSTECTOMY FOR BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Invasive IV (PD55)1 Sep 2021PD55-05 METASTASIS-DIRECTED RADIATION THERAPY AFTER RADICAL CYSTECTOMY FOR BLADDER CANCER Andre Miranda, Jeffrey Howard, Mark McLaughlin, Xiaosong Meng, Aurelie Garant, Aditya Bagrodia, Vitaly Margulis, Yair Lotan, Raquibul Hannan, Neil Desai, and Solomon Woldu Andre MirandaAndre Miranda More articles by this author , Jeffrey HowardJeffrey Howard More articles by this author , Mark McLaughlinMark McLaughlin More articles by this author , Xiaosong MengXiaosong Meng More articles by this author , Aurelie GarantAurelie Garant More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Vitaly MargulisVitaly Margulis More articles by this author , Yair LotanYair Lotan More articles by this author , Raquibul HannanRaquibul Hannan More articles by this author , Neil DesaiNeil Desai More articles by this author , and Solomon WolduSolomon Woldu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002089.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Metastasis-directed radiation therapy (MDRT) may improve oncologic and quality of life outcomes in patients with metastatic cancer, but data on its use in metastatic bladder cancer is severely limited and is primarily from the pre-immunotherapy era. We sought to review our recent institutional experience with MDRT in patients with metastatic bladder cancer following radical cystectomy. METHODS: We reviewed records of patients who underwent radical cystectomy and subsequent MDRT at our institution between 2009 and 2020. Baseline demographic and clinical/pathologic factors were collected, as were details of treatment including systemic therapy and MDRT. Cases were categorized by treatment intent as consolidative (intended to prolong survival) and palliative (intended only to relieve symptoms). Response to treatment, survival, and toxicity outcomes were reviewed. RESULTS: A total of 52 patients underwent MDRT following radical cystectomy. MDRT was categorized as consolidative in 40% of cases and palliative in 60%. Toxicity (CTCAE Grade ≥2) was reported in 15% of patients, none of which exceeded Grade 3. Most patients undergoing consolidative MDRT were treated with SBRT techniques (76%) and a majority (67%) received concurrent treatment with an immuno-oncology agent. Among patients treated with consolidative intent, 2-year progression-free and overall survival were 19% and 60%, respectively. CONCLUSIONS: This represents one of the largest published series of metastasis-directed radiation therapy (MDRT) in metastatic bladder cancer. MDRT is safe and well-tolerated by a majority of patients. A majority of patients treated with consolidative intent survived ≥2 years from treatment, suggesting that some appropriately selected patients can achieve long-term survival. Further prospective research is required to define the role of MDRT in metastatic bladder cancer. Source of Funding: This study was funded internally by the UT Southwestern Department of Urology. © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e998-e999 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andre Miranda More articles by this author Jeffrey Howard More articles by this author Mark McLaughlin More articles by this author Xiaosong Meng More articles by this author Aurelie Garant More articles by this author Aditya Bagrodia More articles by this author Vitaly Margulis More articles by this author Yair Lotan More articles by this author Raquibul Hannan More articles by this author Neil Desai More articles by this author Solomon Woldu More articles by this author Expand All Advertisement Loading ...

MO27-3 Clinical outcomes of metastasis-directed radiation therapy (MDRT) for oligometastatic prostate cancer

MO27-3 Clinical outcomes of metastasis-directed radiation therapy (MDRT) for oligometastatic prostate cancer

Metastasis-directed radiation therapy after radical cystectomy for bladder cancer

PurposeMetastasis-directed radiation therapy (MDRT) may improve oncologic and quality of life outcomes in patients with metastatic cancer, but data on its use in metastatic bladder cancer is severely limited. We sought to review our institutional experience with MDRT in patients with metastatic bladder cancer following radical cystectomy. Materials and MethodsWe reviewed records of patients who underwent radical cystectomy and subsequent MDRT at our institution between 2009 and 2020. Baseline demographic and clinical/pathologic factors were collected, as were details of treatment including systemic therapy and MDRT. Cases were categorized by treatment intent as consolidative (intended to prolong survival) and palliative (intended only to relieve symptoms). Response to treatment, survival, and toxicity outcomes were reviewed. ResultsA total of 52 patients underwent MDRT following radical cystectomy. MDRT was categorized as consolidative in 40% of cases and palliative in 60%. Toxicity (CTCAE Grade ≥ 2) was reported in 15% of patients, none of which exceeded Grade 3. Most patients undergoing consolidative MDRT were treated with SBRT techniques (76%) and a majority (67%) received concurrent treatment with an immuno-oncology agent. Among patients treated with consolidative intent, 2-year progression-free and overall survival were 19% and 60%, respectively. ConclusionMDRT is safe and well-tolerated by a majority of patients. A majority of patients treated with consolidative intent survived ≥ 2 years from treatment.

Combining 68Ga-PSMA-PET/CT-Directed and Elective Radiation Therapy Improves Outcome in Oligorecurrent Prostate Cancer: A Retrospective Multicenter Study.

BackgroundIn case of oligo-recurrent prostate cancer (PC) following prostatectomy, 68Ga-PSMA-PET/CT can be used to detect a specific site of recurrence and to initiate metastasis-directed radiation therapy (MDT). However, large heterogeneities exist concerning doses, treatment fields and radiation techniques, with some studies reporting focal radiotherapy (RT) to PSMA-PET/CT positive lesions only and other studies using elective RT strategies. We aimed to compare oncological outcomes and toxicity between PET/CT-directed RT (PDRT) and PDRT plus elective RT (eRT; i.e. prostate bed, pelvic or paraaortal nodes) in a large retrospective multicenter study.MethodsData of 394 patients with oligo-recurrent 68Ga-PSMA-PET/CT-positive PC treated between 04/2013 and 01/2018 in six different academic institutions were evaluated. Primary endpoint was biochemical-recurrence-free survival (bRFS). bRFS was analyzed using Kaplan–Meier survival curves and log rank testing. Uni- and multivariate analyses were performed to determine influence of treatment parameters.ResultsIn 204 patients (51.8%) RT was directed only to lesions seen on 68Ga-PSMA-PET/CT (PDRT), 190 patients (48.2%) received PDRT plus eRT. PDRT plus eRT was associated with a significantly improved 3-year bRFS compared to PDRT alone (53 vs. 37%; p = 0.001) and remained an independent factor in multivariate analysis (p = 0.006, HR 0.29, 95% CI 0.12–0.68). This effect was more pronounced in the subgroup of patients who were treated with PDRT and elective prostate bed radiotherapy (ePBRT) with a 3-year bRFS of 61% versus 22% (p <0.001). Acute and late toxicity grade ≥3 was 0.8% and 3% after PDRT plus eRT versus no toxicity grade ≥3 after PDRT alone.ConclusionsIn this large cohort of patients with oligo-recurrent prostate cancer, elective irradiation of the pelvic lymphatics and the prostatic bed significantly improved bRFS when added to 68Ga-PSMA-PET/CT-guided focal radiotherapy. These findings need to be evaluated in a randomized controlled trial.

Clinical Outcomes of Combined Prostate- and Metastasis-Directed Radiation Therapy for the Treatment of De Novo Oligometastatic Prostate Cancer

PurposeThe Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trial reported overall survival benefits for prostate-directed radiation therapy (PDRT) in low-burden metastatic prostate cancer. Oligometastasis-directed radiation therapy (ORT) improves androgen deprivation therapy (ADT)–free and progression-free survivals. Comprehensive PDRT + ORT to all detectable metastases may offer benefit for de novo oligometastatic prostate cancer (DNOPC) and is under prospective study; given few available benchmarks, we reviewed our institutional experience. Methods and MaterialsForty-seven patients with DNOPC with predominantly M1b disease received neoadjuvant, concurrent, and adjuvant ADT plus PDRT + ORT to 1 to 6 oligometastases. Gross pelvic (N1) nodes were not considered oligometastases unless focally targeted without broader nodal coverage. Outcomes were analyzed from radiation therapy (RT) start using Kaplan-Meier, competing risks, and Cox regression. Median follow-up was 27 (95% confidence interval, 16-42) months. ResultsAt 1- and 2-years post-RT, cumulative incidence of distant metastatic progression (DMP) was 21% and 32%, whereas overall survival was 90% and 87%, respectively. Neuroendocrine/intraductal histology, prostate-specific antigen (PSA) < 20, and detectable PSA after PDRT + ORT were associated with increased DMP risk; number and location of oligometastases were not. Local failure was rare, with 3 prostate recurrences and progression of 10 treated oligometastases during follow-up. After neoadjuvant ADT, 9 (19%) patients had undetectable PSA (<0.05 ng/mL), which increased to 32 (68%) after PDRT + ORT. Overall 2-year incidence of biochemical recurrence (BCR) and development of castrate resistance were 23% and 36%, respectively. Undetectable PSA post-RT was associated with lower risk of BCR (hazard ratio, 0.19; P = .004) and DMP (hazard ratio, 0.26; P = .025). Overall, 23 (49%) patients were trialed off ADT; 16 (70%) had testosterone recovery (>150 ng/dL) and, of these, 5 had subsequent PSA rise and restarted ADT 2 to 21 months postrecovery. The remaining 11 were maintained off ADT without BCR. Median noncastrate duration was 8 months; 7 patients had normalized testosterone for >1 year. ConclusionsA comprehensive, radiotherapeutic-based treatment strategy has favorable clinical outcomes and can produce prolonged noncastrate remissions in a subset with DNOPC.

The efficacy of metastasis-directed radiation therapy (MDRT) for oligometastatic castration-resistant prostate cancer (CRPC).

240 Background: We have utilized imaging study, especially whole body magnetic resonance imaging (WB-MRI), to detect oligometastatic disease of castration resistant prostate cancer (CRPC) and performed metastasis-directed radiation therapy (MDRT) for oligometastatic disease. We review our institutional experience of MDRT for oligometastatic CRPC. Methods: We retrospectively reviewed the database comprising 26 oligometastatic CRPC patients treated by MDRT for oligometastatic disease combined with baseline androgen deprivation therapy at Osaka International Cancer Institute from January 2013 to August 2019 and investigated treatment efficacy of MDRT. Diagnosis of oligometastatic disease was performed by computed tomography, bone scintigraphy and/or WB-MRI. Treatment efficacy was assessed by change of serum prostate specific antigen (PSA) level and progression free survival (PFS). PFS was analyzed by Kaplan-Meier method and comparison was made by log-rank test. Results: The median age at treatment was 75.5 years (range, 62-86). The oligometastatic diseases were bone in 22 patients, lymph node in 2 patients and both in 2 patients. The number of treated lesions were as follows: 1 lesion for 21 patients, 2 lesions for 4 patients and 3 lesions for 1 patient. WB-MRI was performed in 19 patients (73%). Median dose of MDRT was 35Gy (range, 30-60) for bone and 60Gy (range, 50-60) for lymph node. The median PSA prior MDRT was 6.3 ng/ml (range, 0.5-191). Post MDRT PSA reduction was observed in 24 patients (92%) and over 50% PSA reduction was observed in 14 patients (54%). Median PFS was 8.7 month and patients with over 90 days PSA doubling time (PSADT) showed longer PFS (p=0.0074). Conclusions: Our data suggest that MDRT can achieve PSA reduction in most CRPC patients with oligometastasis and PSADT could be a predictor of disease progression after MDRT.

The Evolving Role of Prostate-Specific Membrane Antigen-Based Diagnostics and Therapeutics in Prostate Cancer.

Prostate-specific membrane antigen (PSMA)-based imaging seeks to fill some critical gaps in prostate cancer staging and response assessment, and may select patients for treatment with radiolabeled PSMA conjugates. In biochemical recurrence, at prostate-specific antigen (PSA) levels as low as 0.2 ng/dL, 68Ga-PSMA imaging has demonstrated a 42% detection rate of occult metastatic disease, and detection has been greater than 95% when PSA levels are higher than 2 ng/dL. This may facilitate novel approaches, including salvage lymphadenectomy or metastasis-directed radiation therapy, in patients with oligometastatic disease. PSMA-based imaging has shown promise in evaluating treatment response in hormone-sensitive and castration-resistant disease; however, additional longitudinal assessment is needed given the heterogeneity in uptake changes after the initiation of androgen-deprivation therapy. Changes in uptake must be taken in context of RECIST measurements and other response parameters, given the potential for growth of PSMA-negative lesions and persistent uptake in treated bone lesions of uncertain significance. For selecting patients to receive PSMA-targeted radioconjugate therapy, standardized uptake value thresholds remain to be established. Nevertheless, preliminary data from 177Lu-PSMA theranostic trials have yielded PSA responses in up to 57% of patients, as well as pain relief and improved quality of life. Thrombocytopenia was the most common grade 3 or greater toxicity; however, grade 1 xerostomia occurred frequently and was cited as the most common reason for treatment discontinuation.

Outcomes of Curative-Intent Treatment for Patients With Breast Cancer Presenting With Sternal or Mediastinal Involvement

Optimal treatment of patients diagnosed with de novo metastatic breast cancer limited to the mediastinum or sternum has never been delineated. Herein, we sought to determine the efficacy of multimodality treatment, including metastasis-directed radiation therapy, in curing patients with this presentation. This is a single-institution retrospective cohort study of patients with de novo metastatic breast cancer treated from 2005 to 2014, with a 50-month median follow-up for the primary cohort. The primary patient cohort had metastasis limited to the mediastinum/sternum treated with curative intent (n=35). We also included a cohort of patients with stage IIIC disease treated with curative intent (n=244). Additional groups included a mediastinal/sternal palliative cohort (treatment did not include metastasis-directed radiation therapy; n=14) and all other patients with de novo stage IV disease (palliative cohort; n=1185). The primary study outcomes included locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Cox multivariable models compared survival outcomes across treatment cohorts adjusted for molecular subtype, age, and race. For the mediastinal/sternal curative-intent cohort, 5-year LRRFS was 85%, RFS was 52%, and OS was 63%. After adjustment, there was no statistically significant difference in LRRFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.13-1.13; P=.08), RFS (HR, 0.87; 95% CI 0.50-1.49; P=.61), or OS (HR, 0.79; 95% CI 0.44-1.43; P=.44) between the stage IIIC cohort and the mediastinal/sternal curative-intent cohort (referent). In contrast, RFS was worse for the mediastinal/sternal palliative cohort (HR, 2.29; 95% CI 1.05-5.00; P=.04). OS was worst for the de novo stage IV palliative cohort (HR, 2.61; 95% CI 1.50-4.53; P<.001). For select patients presenting with breast cancer metastatic to the sternum and/or mediastinum, curative-intent treatment with chemotherapy, surgery, and radiation yields outcomes similar to those of stage IIIC disease and superior to de novo stage IV breast cancer treated with palliative intent.