Oligorecurrent Prostate Cancer Research Articles

Salvage lymph node dissection in nodal oligorecurrent prostate cancer: literature review and our experience

Salvage lymph node dissection in nodal oligorecurrent prostate cancer: literature review and our experience

Biochemical Response of

BackgroundIn a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value. ObjectiveTo evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS. Design, setting, and participantsThis cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014–2022). InterventionPSMA-RGS. Outcome measurements and statistical analysisPostsalvage surgery PSA response was categorized as <0.1, 0.1–<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response. Results and limitationsAmong 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2–16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1–<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1–<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1–0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1–3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2–4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group. ConclusionsFor patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy. Patient summaryWe studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen–targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time.

Limited prognostic role of routine serum markers (AP, CEA, LDH and NSE) in oligorecurrent prostate cancer patients undergoing PSMA-radioguided surgery

IntroductionWe evaluated the prognostic role of pre-salvage prostate-specific membrane antigen–radioguided surgery (PSMA-RGS) serum levels of alkaline phosphatase (AP), carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and neuron-specific enolase (NSE).Materials and methodsPatients who consecutively underwent PSMA-RGS for prostate cancer (PCa) oligorecurrence between January 2019 and January 2022 were selected. Biomarkers were assessed one day before surgery. Cox regression and logistic regression models tested the relationship between biochemical recurrence-free survival (BFS), 6- and 12-month biochemical recurrence (BCR), and several independent variables, including biomarkers.Results153 consecutive patients were analyzed. In the univariable Cox regression analysis, none of the biomarkers achieved predictor status (AP: hazard ratio [HR] = 1.03, 95% CI 0.99, 1.01; p = 0.19; CEA: HR = 1.73, 95% CI 0.94, 1.21; p = 0.34; LDH: HR = 1.01, 95% CI 1.00, 1.01; p = 0.05; NSE: HR = 1.02, 95% CI 0.98, 1.06; p = 0.39). The only independent predictor of BFS was the number of positive lesions on PSMA PET (HR = 1.17, 95% CI 1.02, 1.30; p = 0.03).The number of positive lesions was confirmed as independent predictor for BCR within 6 and 12 months (BCR < 6 months: odds ratio [OR] = 1.1, 95% CI 1.0, 1.3; p = 0.04; BCR < 12 months: OR = 1.1, 95% CI 1.0, 1.3; p = 0.04).ConclusionThe assessment of AP, CEA, LDH, and NSE before salvage PSMA-RGS showed no prognostic impact. Further studies are needed to identify possible predictors that will optimize patient selection for salvage PSMA-RGS.

Metastasis-directed therapy: new standard or too early to change paradigm?

SummaryMetastasis-directed therapy (MDT) is an emerging treatment strategy for patients with oligometastatic prostate cancer (PCa), particularly for oligorecurrent disease. This review aims to summarize findings from several prospective trials in the setting of oligorecurrent PCa. We found that MDT is feasible, has high tolerability, and is effective in terms of local control of treated lesions and of deferring disease progression in well-selected patients. Selecting patients for MDT requires thoughtful consideration of factors such as the castration status, the number of detected metastases, and the imaging modality used for metastasis detection. Notably, the studies included in this review varied in terms of these factors, complicating the comparability of their results. Despite the existence of several prospective clinical trials in the field, there is an absence of high-level evidence attributable to the lack of phase 3 clinical trials. As a result, current guidelines recommend the administration of MDT exclusively within the context of clinical trials. Despite this, retrospective series indicate that MDT is already frequently utilized outside of clinical trials.

Association of PSMA PET-derived Parameters and Outcomes of Patients Treated for Oligorecurrent Prostate Cancer.

Background Prostate-specific membrane antigen (PSMA) PET is useful in the early detection of oligorecurrent prostate cancer (PCa), but whether PSMA PET parameters can be used to identify patients who would benefit from metastasis-directed therapy (MDT) with radiation or surgery remains uncertain. Purpose To assess the association of PSMA PET parameters with outcomes of patients with oligorecurrent PCa after MDT. Materials and Methods In this retrospective analysis of a single-center phase II trial that enrolled patients with biochemical recurrence of PCa after maximal local therapy and with no evidence of disease at conventional imaging, patients underwent PSMA PET (between May 2017 and November 2021), and unveiled recurrences were treated with MDT. Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) and PSMA tumor volume derived using thresholds of 2.5 (SUVmean2.5) and 41% (SUVmean41%), respectively, were recorded for sites of recurrence on PSMA PET scans, and a molecular imaging PSMA score was assigned. These parameters were also corrected for smooth filter and partial volume effects, and the PSMA score was reassigned. Cox proportional hazards models were used to evaluate the relationship between PSMA PET parameters and outcomes. Results A total of 74 men (mean age, 68.3 years ± 6.6 [SD]) with biochemical recurrence of PCa were included. PSMA PET revealed 145 lesions in the entire cohort, of which 125 (86%) were metastatic lymph nodes. Application of the correction factor changed the PSMA score in 88 of 145 lesions (61%). Mean SUVmax, SUVmean2.5, and SUVmean41% were associated with lower risk of biochemical progression (hazard ratio [HR] range, 0.77-0.95; 95% CI: 0.61, 1.00; P = .03 to P = .04). For corrected parameters, mean SUVmax, mean SUVmean2.5, mean SUVmean41%, mean PSMA score, maximum SUVmean2.5, maximum SUVmean41%, and maximum PSMA score were associated with a lower risk of biochemical progression (HR, 0.61-0.98; 95% CI: 0.39, 1.00; P = .01 to P = .04). Conclusion Measured and corrected PSMA PET parameters were associated with biochemical progression in men with oligorecurrent PCa treated with MDT. Clinical trial registration no. NCT03160794 © RSNA, 2023 See also the editorial by Civelek in this issue.

P127 - Oncological outcomes of patients with oligorecurrent prostate cancer on PMSA PET/CT who underwent stereotactic body radiotherapydiotherapy

P127 - Oncological outcomes of patients with oligorecurrent prostate cancer on PMSA PET/CT who underwent stereotactic body radiotherapydiotherapy

EAU Biochemical Recurrence Risk Classification and PSA Kinetics Have No Value for Patient Selection in PSMA-Radioguided Surgery (PSMA-RGS) for Oligorecurrent Prostate Cancer.

To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS. We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS). Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR (p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70-3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46-2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR (p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95-1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97-1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99-1.04, p = 0.2). Consistent negative findings were recorded for PSA-V. The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.

A Pilot Study of Stereotactic Body Radiotherapy and 177Lu-PSMA-617 for Oligometastatic Hormone Sensitive Prostate Cancer

Stereotactic body radiotherapy (SBRT) is increasingly used for oligorecurrent prostate cancer (OPC). Despite excellent local control, distant metastasis free survival rates are more modest. We hypothesized SBRT outcomes could be optimized with improved staging imaging and integration of a well-tolerated targeted radiopharmaceutical therapy (RLT) for microscopic disease. We report initial results of a prospective, single-institution pilot (NCT05079698) of a novel, PSMA-based theranostic strategy for OPC. Men with castrate sensitive OPC and 1-3 sites of PSMA PET avid disease ("index lesions") and no PSMA non-avid sites were eligible. No androgen deprivation therapy was permitted. Subjects first received 2 cycles of 177Lu-PSMA-617 RLT (7.47±0.14 GBq) spaced 6 weeks apart. In vivo dosimetry was performed during cycle 1. Four weeks post-cycle 2, patients were restaged with 68Ga-PSMA PET for an interim (post-RLT) response assessment. Index lesions were then consolidated with SBRT (9 Gy x 3) irrespective of post-RLT PET response. The primary outcome was feasibility defined as successful completion of protocol-mandated therapy without intercurrent distant failure on post-RLT PET. Six men were treated with nine total index lesions (5 nodal, 3 osseous, 1 visceral). The study met its primary endpoint; all completed required interventions and no distant progression was seen on interim PSMA PET. Treatment was well tolerated; no grade 3+ toxicities, 2/6 had grade 2 toxicities (transient anemia and hyperbilirubinemia) and 5/6 had grade 1 toxicities. Median baseline lesion-level PSMA SUVmax was 16.8±8.7. Median interim SUVmax was 6.2±2.5 and declined for all but one lesion post-RLT (median -65%). Median SUVmax at 3-mos post-SBRT was 3.3±2.5 and decreased for all evaluable lesions (median -80%). Median baseline PSA was 2.01 ng/mL (range: 0.72-4.56) which declined in 5/6 post-RLT. The 6th patient experienced biochemical rise with interim PET showing only greater avidity in the known index lesion and SBRT was completed per protocol. All 4 evaluable patients with at least one post-SBRT follow-up have improved PSA at last visit (range 5.5-12 mos from cycle 1), and 2/4 have undetectable PSA. Composite dosimetry, correlatives and quality of life studies are forthcoming. Our pilot study demonstrates the feasibility of a novel PSMA anchored theranostic strategy combining SBRT with targeted RLT for OPC. Preliminary data suggests promising outcomes, including the possibility of achieving an undetectable biochemical disease state without hormone therapy.

Global research status and hotspots of radiotherapy for prostate cancer: a bibliometric analysis based on Web of Science from 2010-2022.

Radiotherapy (RT) is one of the important treatments for various cancer types and its application to prostate cancer (PCa) has also gradually gained increasing attention. However, there is a lack of comprehensive and objective studies on the overall status of research on RT for PCa. This article aims to summarize and quantify the dynamic trends of RT in PCa by using bibliometrics. Studies on RT for PCa were screened from the Web of Science Core Collection (WoSCC) database between 1 January 2010 and 21 November 2022 to collate and quantify information characteristics by analyzing parameters including annual publications, countries/regions, institutions and authors with the aid of the bibliometric software CiteSpace and VOSviewer. In addition, research trends and hotspots were explored by analyzing keywords and co-cited references. A total of 21338 documents were retrieved. The United States of America (USA) ranked first and maintained the leading position among all countries in the number of publications (8489) and total citations (266342). The University of Toronto was the most active institution in total publications (n=587). Paul L Nguyen enjoyed the most publications (n=179), and Michael J Zelefsky enjoyed the most co-citations (n=3376). INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS published the most papers (n=1026), and was the most frequently co-cited journal (n=78550). The largest and closest cluster in the reference cluster analysis was "oligorecurrent prostate cancer". The timeline view of keywords reveals that cluster "biochemical recurrence(BCR)" is ongoing. Moreover, keywords burstness analysis showed that "radiation dosimetry", "dose rate brachytherapy(BT)", "salvage radiotherapy", "stereotactic body radiotherapy(SBRT)", "guideline", and "multicenter" were the terms with great bursts in the past a few years. The application of RT targeting oligometastatic prostate cancer(OMPC) has garnered considerable attention among researchers. SBRT and BT have become hot topics in the field. Additionally, the BCR of PCa has long been a critical issue requiring extensive research and resolution, and salvage radiotherapy has currently emerged as a closely related research focus. Related large-scale multicenter studies have been conducted over the past few years, providing valuable insights. More high-quality research is expected to be employed to guide clinical decision-making.

OC-0434 Long -term results of OLIGOPELVIS, a Phase II Trial of pelvic RT in Oligorecurrent Prostate Cancer

OC-0434 Long -term results of OLIGOPELVIS, a Phase II Trial of pelvic RT in Oligorecurrent Prostate Cancer

PSMA-PET Guided Treatment in Prostate Cancer Patients with Oligorecurrent Progression after Previous Salvage Treatment

Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients. we performed a retrospective analysis of 113 recurrent PCa after previous radical prostatectomy and salvage therapies with oligorecurrent disease at PSMA-PET (≤3 lesions in N1/M1a-b) in three high-volume European centres. Patients underwent second-line salvage treatments: MDT targeted to PSMA (including surgery and/or radiotherapy), and the conventional approach (observation or Androgen Deprivation Therapy [ADT]). Patients were stratified according to treatments (MDT vs. conventional approach). Patients who underwent MDT were stratified according to stage in PSMA-PET (N1 vs. M1a-b). The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were Metastases-free survival (MFS) and Castration Resistant PCa free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS. Multivariable Cox regression models identified predictors of progression and metastatic disease. Overall, 91 (80%) and 22 (20%) patients were treated with MDT and the conventional approach, respectively. The median follow-up after PSMA-PET was 31 months. Patients who underwent MDT had a similar PFS compared to the conventional approach (p = 0.3). Individuals referred to MDT had significantly higher MFS and CRPC-FS compared to those who were treated with the conventional approach (73.5% and 94.7% vs. 30.5% and 79.5%; all p ≤ 0.001). In patients undergoing MDT, no significant differences were found for PFS and MFS according to N1 vs. M1a-b disease, while CRPC-FS estimates were significantly higher in patients with N1 vs. M1a-b (100% vs. 86.1%; p = 0.02). At multivariable analyses, age (HR = 0.96) and ADT during second line salvage treatment (HR = 0.5) were independent predictors of PFS; MDT (HR 0.27) was the only independent predictor of MFS (all p ≤ 0.04) Conclusion: Patients who underwent second-line PSMA-guided MDT experienced higher MFS and CRPC-FS compared to men who received conventional management.

Comparison of Hormone-Sensitive Oligorecurrent Prostate Cancer Patients Based on Routine Use of Choline and/or PSMA PET/CT to Guide Metastasis-Directed Therapy

In hormone-sensitive oligorecurrent prostate cancer (PC), the literature showed [68Ga]Ga-PSMA (PSMA) and [18F]F-choline (FCH) PET/CT can successfully guide metastasis-directed therapies (MDT). This observational retrospective study aimed to explore, in routine use, the impact of FCH or PSMA PET/CT in guiding MDT for hormone-sensitive oligometastatic PC at different recurrences. In 2017-2020, patients initially treated with radical prostatectomy but, in biochemical recurrence (with PSA ≤ 2 ng/mL), diagnosed as oligometastatic based on FCH or PSMA PET/CT, were identified. MDT was stereotactic body radiotherapy (SBRT), elective nodal or prostate bed radiotherapy ± boost and ± androgen deprivation therapy (ADT). The primary endpoint was biochemical relapse-free survival (BR-FS), defined as a PSA increase ≥ 0.2 ng/mL above the nadir and increasing over two successive samples and the secondaries were ADT-free survival (ADT-FS). 123 patients (70 PSMA and 53 FCH) were included. The median follow-up was 42.2 months. The median BR-FS was 24.7 months in the PSMA group versus 13.0 months in the FCH group (p = 0.008). Similarly, ADT-FS (p = 0.001) was longer in patients in the PSMA group. In multivariate analysis, a short PSA doubling time before imaging (p = 0.005) and MDT with SBRT (p = 0.001) were poor prognostic factors for BR-FS. Routine use of FCH or PSMA PET/CT in hormone-sensitive PC showed an advantage for using PSMA PET/CT to guide MDT in terms of BR-FS and ADT-FS in patients with low PSA value. Prospective studies are needed to confirm these hypotheses.

Predictors of Recurrence After Metastasis-directed Therapy in Oligorecurrent Prostate Cancer Following Radical Prostatectomy

BackgroundMetastasis-directed therapy (MDT) is performed to delay systemic treatments for oligorecurrent disease after primary prostate cancer (PCa) treatment. ObjectiveThe aim of this study was to identify the predictors of therapeutic response of MDT for oligorecurrent PCa. Design, setting, and participantsbicentric, retrospective study, including consecutive patients who underwent MDT for oligorecurrent PCa after radical prostatectomy (RP; 2006–2020) was conducted. MDT encompassed stereotactic body radiation therapy (SBRT), salvage lymph node dissection (sLND), whole-pelvis/retroperitoneal radiation therapy (WP[R]RT), or metastasectomy. Outcome measurements and statistical analysisndpoints were 5-yr radiographic progression-free survival (rPFS), metastasis-free survival (MFS), palliative androgen deprivation treatment (pADT)-free survival, and overall survival (OS) together with prognostic factors for MFS following primary MDT. Survival outcomes were studied by Kaplan-Meier survival and univariable Cox regression (UVA). Results and limitationsA total of 211 MDT patients were included; 122 (58%) developed a secondary recurrence. Salvage lymph node dissection was performed in 119 (56%), SBRT in 48 (23%), and WP(R)RT in 31 (15%) of the cases. Two patients received sLND + SBRT and one received sLND + WPRT. Eleven (5%) patients received metastasectomies. The median follow-up since RP was 100 mo, while follow-up after MDT was 42 mo. The 5-yr rPFS, MFS, androgen deprivation treatment(–free survival, castration-resistant prostate cancer–free survival, CSS, and OS after MDT were 23%, 68%, 58%, 82%, 93%, and 87% respectively. There was a statistically significant difference between cN1 (n = 114) and cM+ (n = 97) for 5-yr MFS (83% vs 51%, p < 0.001), pADT-free survival (70% vs 49%, p = 0.014), and CSS (100% vs 86%, p = 0.019). UVA was performed to assess the risk factors (RFs) for MFS in cN1 and cM+. Alpha was set at 10%. RFs for MFS in cN1 were lower initial prostate-specific antigen (PSA) at the time of RP (hazard ratio [95% confidence interval] 0.15 [0.02–1.02], p = 0.053], pN stage at RP (2.91 [0.83–10.24], p = 0.096), nonpersisting PSA after RP (0.47 [0.19–1.12], p = 0.089), higher PSA at primary MDT (2.38 [1.07–5.24], p = 0.032), and number of positive nodes on imaging (1.65 [1.14–2.40], p < 0.01). RFs for MFS in cM+ were higher pathological Gleason score (1.86 [0.93–3.73], p = 0.078), number of lesions on imaging (0.77 [0.57–1.04], p = 0.083), and cM1b/cM1c (non-nodal metastatic recurrence; 2.62 [1.58–4.34], p < 0.001). ConclusionsFollowing MDT, 23% of patients were free of a second recurrence at 5-yr follow-up. Moreover, cM+ patients had significantly worse outcomes in terms of MFS, pADT-free survival, and CSS. The RFs for a metastatic recurrence can be used for counseling patients, to inform prognosis, and potentially select candidates for MDT. Patient summaryIn this paper, we looked at the outcomes of using localized, patient-tailored treatment for imaging-detected recurrent prostate cancer in lymph nodes, bone, or viscera (maximum five recurrences on imaging). Our results showed that targeted treatment of the metastatic lesions could delay the premature use of hormone therapy.

Elective nodal radiotherapy with a gapless radiation field junction for oligorecurrent prostate cancer after previous radiotherapy

PurposeTo evaluate the feasibility of subsequent elective nodal radiotherapy (ENRT) for nodal recurrences after previous radiotherapy with a defined planning approach for a gapless radiation field junction. MethodsPatients with 1) previous radiotherapy of prostate or prostatic fossa and subsequent pelvic ENRT or 2) previous pelvic radiotherapy and subsequent ENRT to paraaortic lymph nodes (LN) and gapless junction of both radiation fields were analyzed. The cumulative maximum dose (Dmax-cum) and the maximum cumulative dose in 1 cc (D1cc-cum) were estimated. Absolute toxicity and the toxicity exceeding baseline were evaluated. ResultsTwenty-two patients with PSMA-PET/CT-staged nodal oligorecurrence after prior radiotherapy were treated with pelvic (14 patients) or paraaortic ENRT (9 patients). One patient was treated sequentially at both locations. Median time between first and second RT was 20.2 months. Median doses to the lymphatic pathways and to PET-positive LN were 47.5 Gy and 64.8 Gy, respectively. The planning constraint of an estimated Dmax-cum ≤ 95 Gy and of D1cc-cum < 90 Gy were achieved in 23/23 cases and 22/23 cases, respectively. Median follow-up was 33.5 months. There was no additional acute or late toxicity ≥ grade 3. Worst acute toxicity exceeding baseline was grade 1 in 68.2% and grade 2 in 22.7% of patients. Worst late toxicity exceeding baseline was grade 1 in 31.8% and grade 2 in 18.2% of patients. ConclusionENRT for nodal recurrences after a previous radiotherapy with gapless junction of radiation fields seems to be feasible, applying the dose constraints Dmax-cum ≤ 95 Gy and D1cc-cum < 90 Gy without grade 3 acute or late toxicities exceeding baseline.

SPARKLE: a new spark in treating oligorecurrent prostate cancer: adding systemic treatment to stereotactic body radiotherapy or metastasectomy: key to long-lasting event-free survival?

BackgroundMetastasis-directed therapy (MDT) significantly delays the initiation of palliative androgen deprivation therapy (pADT) in patients with oligorecurrent prostate cancer (PCa) with a positive impact on patient’s quality of life. However, it remains unclear whether the addition of ADT improves polymetastatic free survival (PMFS) and metastatic castration refractory PCa-free survival (mCRPC-FS) and how long concomitant hormone therapy should be given. A significant overall survival (OS) benefit was shown when an androgen receptor targeted agent (ARTA) was added to pADT in patients with metastatic hormone sensitive PCa (HSPC). However, whether the addition of and ARTA to MDT in the treatment of oligorecurrent PCa results in better PMFS and mCRPC-FS has not been proven yet.Methods & designPatients diagnosed with oligorecurrent HSPC (defined as a maximum of 5 extracranial metastases on PSMA PET-CT) will be randomized in a 1:1:1 allocation ratio between arm A: MDT alone, arm B: MDT with 1 month ADT, or arm C: MDT with 6 months ADT together with ARTA (enzalutamide 4 × 40 mg daily) for 6 months. Patients will be stratified by PSA doubling time (≤ 3 vs. > 3 months), number of metastases (1 vs. > 1) and initial localization of metastases (M1a vs. M1b and/or M1c). The primary endpoint is PMFS, and the secondary endpoints include mCRPC-FS, biochemical relapse-free survival (bRFS), clinical progression free survival (cPFS), cancer specific survival (CSS), overall survival (OS), quality of life (QOL) and toxicity.DiscussionThis is the first prospective multicentre randomized phase III trial that investigates whether the addition of short-term ADT during 1 month or short-term ADT during 6 months together with an ARTA to MDT significantly prolongs PMFS and/or mCRPC-FS.Trial registrationClinicalTrials.gov Identifier: NCT05352178, registered April 28, 2022.

Metastasis-directed Therapy Without Androgen Deprivation Therapy in Solitary Oligorecurrent Prostate Cancer.

As controversy remains regarding the role of metastasis-directed therapy in patients with oligometastatic prostate cancer, we sought to characterize outcomes of metastasis-directed therapy without concomitant androgen deprivation therapy in the specific subset of patients with a solitary metastatic lesion on C-11 choline positron emission tomography imaging whose primary tumor has already been treated. We identified 124 consecutive prostate cancer patients from 2008 to 2018 with a solitary oligorecurrent metastatic lesion on positron emission tomography imaging who were treated with metastasis-directed therapy without androgen deprivation therapy from the Mayo Clinic C-11 choline registry. Metastasis-directed therapy consisted of either stereotactic body radiation therapy or surgical excision. Of these 124 patients, 67 were treated with surgery (median follow-up 54 months) and 57 patients were treated with stereotactic body radiation therapy (median follow-up 53 months). Of patients treated with surgery, 80.5% had &gt;50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 29%. Median time to initiation of systemic therapy in this cohort was 18.5 months (interquartile range 8.4-44.7 months). Meanwhile, for patients treated with stereotactic body radiation therapy, 40.3% had &gt;50% decline in prostate specific antigen at first follow-up, and the 3-year radiographic progression-free survival was 17%. Similarly, median time to initiation of systemic therapy was 17.8 months (interquartile range 7.1-42.3 months). This study represents the first reported series of metastasis-directed therapy without androgen deprivation therapy in patients with solitary oligorecurrent metastatic prostate cancer. These results suggest that metastasis-directed therapy without androgen deprivation therapy can delay initiation of systemic therapy and highlight the need for further prospective study for select patients with solitary metastatic recurrences of prostate cancer.

174TiP SPARKLE: A new spark in treating oligorecurrent prostate cancer: Adding systemic treatment to stereotactic body radiotherapy or metastasectomy: Key to long-lasting event-free survival?

Metastasis-directed therapy (MDT), performed by either metastasectomy or stereotactic body radiation therapy (SBRT) significantly delays the initiation of palliative androgen deprivation therapy (pADT) in patients with oligorecurrent prostate cancer (PCa). This delay positively impacts patient’s quality of life. For this approach, however, it remains unclear whether adding a certain period of ADT improves polymetastatic disease-free survival (PM-DFS) and castration refractory PCa-free survival (CRPC-FS).

O2 - Does metastases-direct therapy guided by PSMA PET/CT really improve oncologic outcomes in oligorecurrent prostate cancer patients?

O2 - Does metastases-direct therapy guided by PSMA PET/CT really improve oncologic outcomes in oligorecurrent prostate cancer patients?

Para-Aortic Radiation Therapy for Oligorecurrent Prostate Cancer

<h3>Purpose/Objective(s)</h3> Patients with oligorecurrent prostate cancer (PCa) limited to the pelvic lymph nodes (LNs) are often treated with whole pelvis radiotherapy (RT) with excellent clinical outcomes, as demonstrated in a phase 2 clinical trial. For oligorecurrent PCa in the para-aortic (PA) LNs, although the standard of care is systemic therapy only, RT may also be beneficial. The purpose of this study is to retrospectively assess the safety and efficacy of RT to the PA LNs (PA-RT) in this population. <h3>Materials/Methods</h3> We identified a sequential cohort of patients with oligorecurrent PCa to the PA LNs (≤5) after pelvic RT at our institution from 2015 to 2021. Eligible patients had oligorecurrent PCa to the PA LNs treated with elective, conventionally fractionated PA-RT plus simultaneous integrated boost (SIB) to LN+ disease. The primary endpoint was defined as progression-free survival (PFS) at 2 years using Kaplan-Meier estimation. PFS was defined as the time from PA-RT to the first event: biochemical failure (PSA 50% above post-treatment nadir and at least 4 ng/mL), escalation of therapy, clinical progression, or death. Secondary endpoints included 2-year biochemical failure-free survival (BFFS), 2-year overall survival (OS) and treatment-related toxicity. <h3>Results</h3> In total, 34 patients were included (median age 66 years), and 82.4% were status post-prostatectomy. The median time from diagnosis to PA-RT was 5.7 years. The median PSA at PA-RT was 3.15 ng/mL (IQR 1.30-5.90), and 23.5% had castration-resistant PCa (CRPC). All patients were treated to the PA region with 50 Gy (88.2%) or 45 Gy (11.8%) in 25 daily fractions. LN+ disease received a SIB to a median dose of 62.5 Gy (range 60-65 Gy). Most received photon-based RT, while 21.1% were treated with proton therapy. Nearly all (97.1%) patients had androgen deprivation therapy (ADT) monotherapy (median duration 20 months), and 52.9% had ADT plus abiraterone. The median follow-up time from PA-RT was 21.5 months. The primary endpoint, PFS at 2-years, was 83.4% (95% CI: 68.6-100%). 2-year BFFS was 90.4% and OS 100%. 8 patients had castration resistant PCa with trend to worse PFS (p=0.14). There were no grade 3 or higher acute toxicities. There were 10 (29.4%) grade 2 acute toxicities, 8 were gastrointestinal. There were 2 (5.9%) grade 3 chronic toxicities (small bowel obstruction and hematuria requiring intervention). There were 4 (11.8%) chronic grade 2 toxicities. <h3>Conclusion</h3> PA-RT for oligorecurrent PCa has low toxicity with encouraging early disease control. These preliminary results show similar outcomes to RT for oligorecurrent PCa limited to the pelvis; however, these results require validation in prospective studies.

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.