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Simultaneous PET/MRI imaging has the advantage of combining metabolic information from PET with the high-spatial resolution of MRI to identify disease with greater accuracy than conventional imaging. F-18 rhPSMA 7.3 (rhPSMA) ligands are a new class of diagnostic/therapeutic PSMA-targeting agents in prostate cancer (PCa). We hypothesized that F-18 rhPSMA 7.3 PET/MRI accurately detects recurrent PCa to direct field design in salvage radiation therapy (RT) planning even at low PSA levels. This is a prospective phase II pilot study enrolling men with biochemical recurrence (BCR) after prostatectomy for PCa who underwent rhPSMA 7.3 PET on a simultaneous 3T PET/MRI scanner. The radiation oncologists answered surveys to document changes to RT plan based on the PET/MRI results. All patients underwent standard fractionated RT with at least 6 months of hormonal therapy (HR). Patients with positive scan returned 6-18 months after the first scan for a second timepoint PET/MRI scan after treatment. Standard of truth was established by pathology when feasible or a combination of confirmatory imaging showing radiographic and PSA response after treatment. The primary aim is to evaluate the positive predictive value (PPV) of rhPSMA PET/MRI in detecting disease. The secondary aims included change in RT plan after rhPSMA PET/MRI and treatment response. 29 patients with a median age of 66 years (IQR: 47-76) at the time of imaging were enrolled between Aug 2021 to Jan 2023, of which 28 patients underwent rhPSMA PET/MRI scan. The Gleason score at diagnosis was ≥7 with a median PSA of 7.0 ng/mL (IQR: 0.9-29.5) before surgery. Median PSA was 0.3 ng/mL (IQR: 0.2-1.5) at BCR presentation with 24 (86%) patients having PSA <0.5. Twenty patients (71%) had rhPSMA positive findings. 4/20 patients with rhPSMA positive lesions did not receive follow up imaging as they chose to undergo treatment elsewhere. Of the 16 patients who underwent a confirmatory scan and/or biopsy, 15/16 (94%) patients were found to be true positive while 1/16 (6%) was a false positive. RT plan was changed in 22/28 (79%) with major changes including extension of clinical target volumes to cover PSMA positive pelvic lesions or cancellation of RT due to polymetastatic disease in 8/22 (36%), minor changes including dose escalation to gross disease or dose de-escalation to the rest of prostate fossa in 9/22 (41%) and both major and minor changes in 5/22 (23%) patients. All 14 patients who underwent a combination of RT and HT had complete response on the second timepoint rhPSMA PET/MRI. Median PSA was <0.1 ng/mL (IQR: <0.1-0.1) ng/mL after treatment before the second scan. Even at low PSA levels, F-18 rhPSMA 7.3 PET/MRI resulted in a high detection rate of true positive lesions. Furthermore, incorporation of this technology led to changes in 79% of RT plans. Simultaneous F-18 rhPSMA 7.3 PET/MRI imaging can potentially serve as a "one stop shop" to stratify patient treatment and tailor salvage radiation fields. (NCT04978675) [ABSTRACT FROM AUTHOR]

The benefit of local consolidative therapy (LCT) for oligometastasis across histologies is undefined. EXT ernal beam radiation to Eliminate Nominal metastatic disease (EXTEND; NCT03573611) is a phase II basket trial randomizing patients with 1-5 metastatic sites to standard of care (SOC) systemic therapy with or without LCT. We hypothesized that patients treated with LCT would have superior progression-free survival (PFS). Prior to the randomization phase of this trial, we initiated a single-arm lead-in component to evaluate enrollment feasibility and identify histology baskets most likely to complete accrual. Here we report the accrual, efficacy, and toxicity results of the lead-in phase. Eligible histologies included colorectal, sarcoma, lung, head and neck, ovarian, kidney, melanoma, pancreatic, prostate, cervix/uterine, breast, and cholangiocarcinoma. All patients were treated with SOC systemic therapy plus LCT to all sites of active metastatic disease and primary/regional disease (as applicable). Enrollment in the lead-in phase was capped after 6 months, or for an individual histology, after accrual of 8 patients with that histology. Definitive LCT included surgery or radiation. Dose, fractionation, and systemic therapy were per oncologist discretion. PFS was defined by radiographically (RECIST v1.1), biochemically (prostate only), or clinically or by death, and was estimated by the Kaplan-Meier method. Common Terminology Criteria for Adverse Events v4.0 was used. From August 2018 through January 2019, 49 patients were enrolled and received LCT. The average age was 63 (range: 32-86). Data cutoff was February 14, 2022. Thirty-six patients had progression and 13 died. The median follow-up time for censored patients was 38 months (range 16-42 months). Prostate (n=8), breast (n=8), and kidney (n=7) represented the most common histologies. Many patients had one metastasis (53%), and 86 total lesions were treated. The most common LCT modality was radiation (97%), which was typically stereotactic (63%). Local control rate was 98% (n=84/86 tumors). Median PFS time was 13 months (95% CI 9–24), and 3-year overall survival rate was 73% (95% CI 57%–83%). Most progression events were new lesions outside the irradiated field (n=30, 83%). Grade 3 toxicity rate was 4% (n=2) and no grade 4+ toxicities were observed. The prospective lead-in phase of EXTEND demonstrated feasibility of rapid accrual to a multi-histology basket trial, encouraging PFS, and low rates of severe toxicity at mature follow-up. The randomized phase is ongoing with histology-based baskets, which will provide histology-specific evidence to guide the application of LCT in oligometastatic disease. [ABSTRACT FROM AUTHOR]

Prior retrospective and prospective evidence have suggested a potential survival benefit of adding metastasis-directed therapy (MDT) to standard of care systemic therapy for oligometastatic breast cancer. This has led to the increased utilization of MDT in this setting despite the lack of randomized evidence to support this approach. Furthermore, the recent presentation of NRG-BR002 has questioned the value of MDT. Thus, we evaluated whether the addition of MDT to systemic therapy improves PFS in oligometastatic breast cancer. EXTEND (NCT03599765) is a phase II randomized basket trial for multiple solid tumors testing whether the addition of MDT improves PFS. The primary endpoint was pre-specified to be independently assessed and reported for the breast basket when a minimum of 6 months of follow-up had been reached. Patients with ≤5 metastases were randomized to standard of care systemic therapy with or without MDT. The choice of systemic therapy was at the discretion of the treating medical oncologist. Number of metastatic lesions and prior lines of systemic therapy for metastatic disease were used as stratification variables pre-randomization. The primary endpoint was progression-free survival (PFS) defined as time to randomization to date of clinical or radiographic progression or death. The study was designed to have 80% power to detect an improvement in median PFS from 18 to 36 months, with a type I error of 0.1. Between September 2018 to July 2022, 43 patients were randomized. 22 patients were assigned to the MDT arm, and 21 patients to the no MDT arm. Three patients were not evaluable. The MDT arm patients were older vs the no-MDT arm patients (median 61.5 years vs 48 years, p = 0.01). Otherwise, the arms were well-balanced. Overall, 8 patients had triple negative disease (18.6%), and 12 patients (30%) had de novo metastatic disease. Of those patients with de novo presentation randomized to MDT, all except one had the primary tumor treated with surgery and radiation. At a median follow-up of 19.4 months, 20 events were observed. Among the 40 evaluable patients, there were 5 deaths (3 in the MDT arm and 2 in the no MDT arm). There was no difference in PFS between the MDT and no MDT arms (median 15.6 v 24.9 months, p = 0.66). Similarly, there was no difference in the secondary endpoint of time to new metastatic lesion appearance between the MDT and no MDT arms (median 15.6 months vs not reached, p = 0.09). Two grade 3 toxicities were observed in the MDT arm, and 1 in the no MDT arm. Further analysis of correlative translational biomarkers, including immune markers and ctDNA, are ongoing. The addition of MDT to standard of care systemic therapy did not improve PFS or time to new metastatic lesion in patients with oligometastatic breast cancer. This data coupled with the recently presented NRG-BR002 results, suggests there is no benefit to MDT in an otherwise unselected oligometastatic breast cancer population. [ABSTRACT FROM AUTHOR]

Patients with de novo clinical T4 (cT4) prostate cancer represent a heterogenous and understudied population. The advanced nature of their local disease often results in obstructive urinary symptoms that lead to significant morbidity and mortality. We analyzed the effects of definitive local therapy on the outcomes of patients with cT4 prostate cancer. We retrospectively reviewed 155 patients with de novo cT4 prostate cancer, treated at a single institution between 1996 and 2020. Baseline obstructive symptoms were defined as lower urinary tract symptoms (LUTS, AUA_SI>20 on flomax), urinary retention requiring foley, or acute renal failure (ARF). The association between baseline and treatment characteristics with outcomes were analyzed using Cox regression univariable analysis (UVA) and multivariable analysis (MVA), p<0.05 was considered significant. Analysis included 155 men, with median follow-up of 71 mos. Most patients had adenocarcinoma (88%), Gleason 9-10 (77%), and median baseline PSA of 19.9ng/ml (range, 0.5-1110). The majority of patients had T4NanyM1 disease (54%), followed by T4N1M0 (24%), and T4N0M0 (22%), as defined by conventional imaging studies. All men received systemic therapy with ADT (80%), ADT+abiraterone (12%), ADT+chemo (4%) or chemotherapy alone (4%). Local therapy was delivered with radiation (RT) (n=44), surgery (n=28), or both (n=9). Median prostate RT dose was 78Gy (IQR, 70-78) in 2Gy fractions. Patients did not receive definitive RT to their metastatic disease. Seventy-two (47%) men presented with obstructive symptoms with 36 (25%) being catheter dependent. For patients with obstructive symptoms, local therapy was associated with improved overall survival (OS: HR 0.33, p=0.001), freedom from local recurrence (FFLR:HR 0.19, p=0.003), and freedom from castration resistance (FFCR:HR 0.28, p=0.002). Patients who received local therapy were less likely to have local progression (HR 0.23, p=0.01), obstructive symptoms with progression (HR 0.21, p=0.03), or die with local disease (HR 0.15, p=0.001). On MVA local therapy improved OS (HR 0.45, p=0.03). OS was also affected by Gleason 10 and M1 disease (HR 15.58, p=0.02, HR 2.99, p=0.004; respectively). Conversely, in men who did not present with obstructive symptoms (n=83), there was no improvement in OS (HR=0.63, P=0.15). Men with cT4 prostate cancer commonly present with obstructive symptoms due to local disease burden, representing a source of significant morbidity and potential mortality. Even among patients with metastatic disease, definitive local therapy is associated with improved patient outcomes including OS. Pending prospective evaluation, these data support the use of local therapy in men with cT4 disease presenting with obstructive urinary symptoms, irrespective of the presence of metastatic disease. [ABSTRACT FROM AUTHOR]

There has been increased utilization of metastasis directed therapy (MDT) for oligometastatic prostate cancer. Despite data demonstrating the benefit of upfront hormone therapy (HT) and synergy between radiation and HT, there exists no randomized trials testing their combination. As it is accepted by most clinicians and men with prostate cancer that time off HT holds intrinsic value, we evaluated whether the addition of metastasis directed therapy (MDT) to intermittent HT in men with oligometastatic prostate cancer facilities time off HT by improving PFS and eugonad PFS. EXTEND (NCT03599765) is a phase II randomized basket trial for multiple solid tumors testing whether the addition of MDT improves PFS. The primary endpoint was pre-specified to be independently assessed and reported for the prostate intermittent HT basket at 41 events. Men with ≤5 metastases were randomized after ≥2 months of HT to continuing HT with or without MDT. HT consisted of a luteinizing hormone-releasing hormone agonist/antagonist with or without a 2nd generation androgen-receptor targeting agent (SART). The primary endpoint was progression, defined as death or radiographic, clinical, or biochemical progression. A planned HT break occurred 6 months after enrollment, after which HT was withheld until progression. The study was designed to have 80% power to detect an improvement in median PFS from 18 to 36 months, with a type I error of 0.1. Exploratory analysis included flow cytometry and TCR sequencing from peripheral blood at baseline and 3 months follow up. Between Sept 2018 to Nov 2020, 87 men were randomized, 43 combined therapy and 44 to HT-only. Arms were well balanced. At a median follow-up of 22.1 months (range 13.0 to 39.3 months), 41 events were observed. PFS was improved by the receipt of MDT (median not reached vs 15.8 months for HT-only, P<0.001; HR=0.25 [95% CI, 0.12 to 0.55]). Among secondary endpoints, time from eugonad testosterone levels (>150 ng/dL) to progression was improved by MDT (median not reached vs 6.1 months, P=0.03), as was time to appearance of new lesions (2-year rate 33% vs 41%, P=0.04). Three grade 3 toxicities were observed in each arm. Subgroup analysis identified PFS improvement with MDT in patients who received (HR=0.24 [95% CI, 0.08 to 0.71]) or did not receive a SART (HR=0.36 [95% CI, 0.15 to 0.83]). Flow cytometry and TCR sequencing demonstrated increases in markers of T cell activation, proliferation, and clonal expansion limited to the combined therapy arm. EXTEND represents the first randomized study to evaluate MDT with HT in oligometastatic prostate cancer and demonstrated improvement in PFS and eugonad PFS. Combination of MDT with intermittent HT may allow for both excellent disease control while facilitating prolonged eugonad testosterone intervals. [ABSTRACT FROM AUTHOR]

Session: Imaging and dosimetry OC-1034: Parallel imaging compressed sensing for prostate MRI without an endorectal coil: a prospective study J. Sanders, S. Frank, A. Venkatesan, T. Bathala, C. Tang, R. Kudchadker, T. Bruno, M. Pagel, J. Ma. [Extracted from the article]