Oligometastatic Prostate Cancer Research Articles

Prospective Characterization of Circulating Tumor Cells in Hormone Sensitive Oligometastatic Prostate Cancer Patients on a Metastasis-Directed Therapy Trial

Prospective data have shown that metastasis-directed therapy (MDT) can alter the natural history of oligometastatic disease. In hormone-sensitive prostate cancer (HSPC), the clinical effect of MDT has been validated by STOMP, ORIOLE and SABR-COMET phase II trials. Circulating tumor cells (CTCs) are likely the source for the formation of macroscopic metastases. CTCs may provide an approach for identifying subgroups of patients with oligometastatic HSPC (oligoHSPC) that would benefit most from MDT. Our main goal was to evaluate the feasibility of CTC detection and subtypes in oligoHSPC patients that may benefit from MDT. ORIOLE randomized men with recurrent HSPC with 1-3 metastases to observation (Obs) vs. stereotactic ablative radiotherapy (SABR) MDT. Blood samples were prospectively collected at baseline (D0) and 6-mos (D180) and shipped for analysis on Epic Sciences liquid biopsy platform (Epic Sciences, San Diego, CA). Machine learning algorithms identified CTCs and characterized androgen receptor (AR) and PSMA expression. Association with clinical factors and outcomes were examined. Biochemical failure-free survival (BFFS) event was a PSA rise of at least 2 ng/mL and 25% above nadir. Progression-free survival (PFS) was a composite endpoint including BFFS event, radiologic progression (RECIST v1.1); symptomatic progression; initiation of ADT; or death. Comparisons of patient and tumor characteristics performed by two-sample t-tests. Survival curves were generated by the Kaplan-Meier method and evaluated by the log-rank test. Effect of SABR on post-SABR on CTC levels were calculated by McNemar test. A total of 82 samples were collected in ORIOLE: 70 SABR (35 D0 and 35 D180) and 12 Obs (7 D0 and 5 D180). 30/42 men had CTCs detected on D0 (71%; AR+ = 7, PSMA+ = 13) and in 26/40 on D180 (65%; AR+ = 9, PSMA+ = 8). Median follow-up was 41.7-mos. There was no association between CTC presence or subtypes (AR+ or PSMA+) with Gleason score or PSA. PFS was significantly lower in the patients with AR+ vs. AR- CTCs on D0 in the SABR arm (p = 0.011, median PFS: AR+ = 9.3- vs. AR+ = 27.1-mos). The median BFFS trended towards a difference for AR+ = 12.9- vs. AR- = 29.2-mos (D180, p = 0.058). SABR had no effect on the presence or subtypes of CTC at D180. Baseline and dynamic CTC levels and their subtypes in oligoHSPC from the ORIOLE randomized trial of MDT was examined. AR+ CTCs at baseline and 6-mos were correlated with clinical outcomes following SABR. Longer follow-up, further analysis and a greater number of patients are needed for a more comprehensive conclusion.

Oligometastatic Prostate Cancer Treated with Stereotactic Body Radiation Therapy: The Role of Three-Dimensional Tumour Volume in Patient Survival

AimsThe definition of oligometastatic prostate cancer (OPCa) is currently based solely on the maximum number of detectable metastases, as there are no validated biomarkers available. The aim of this study was to identify novel predictive factors for OPCa patients who underwent metastases-directed therapy. Materials and methodsThis monocentre, retrospective study included consecutive OPCa patients with a maximum of five metastases in up to two organs, detected with choline- or PSMA-positron emission tomography, who were treated with metastases-directed stereotactic body radiation therapy. Endpoints were overall survival and progression-free survival, assessed with Kaplan–Meier analysis. Univariate and multivariable Cox regression was carried out to evaluate the association between clinical factors and survival outcomes. ResultsBetween 2009 and 2021, 163 patients and 320 metastases were treated with 226 stereotactic body radiation therapy courses. The median three-dimensional metastatic tumour volume was 4.1 cm3, with a range from 0.01 to 233.4 cm3. In total, 87 (53.4%), 21 (12.9%) and 55 (33.7%) metastases were classified as cN1, cM1a and cM1b, respectively. The median follow-up was 28.5 months. The rates of overall survival at 1, 3 and 5 years were 89.5% (95% confidence interval 83.4–93.4), 74.9% (95% confidence interval 66.1–81.7) and 57.2% (95% confidence interval 45.8–67.1), respectively. Multivariable analysis showed that overall survival reduced with the increase in three-dimensional total tumour volume (hazard ratio 1.93, 95% confidence interval 1.06–3.52; P = 0.030) and confirmed a significant difference between cN1 versus cM1a-b disease (hazard ratio 1.81, 95% confidence interval 1.01–3.25; P = 0.046). The cut-off value of total volume correlated with the highest risk of death was 20 cm3 (hazard ratio 2.37, 95% confidence interval 1.34–4.18; P = 0.003). The median progression-free survival was 17.8 months, with 1-, 3- and 5-year rates of 63.7% (95% confidence interval 55.4–70.9), 31.5% (95% confidence interval 22.8–40.6) and 24.7% (95% confidence interval 16.0–34.3). ConclusionsThis study identified three-dimensional total tumour volume and the site of oligometastases as significant predictors of survival in OPCa patients treated with metastases-directed therapy. These parameters can potentially be used to personalised treatment and improve patient outcome.

Lesion Dosimetry for [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer.

A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Methods: Six patients with 9 prostate-specific membrane antigen (PSMA)-positive oligometastases received 2 cycles of [177Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [177Lu]Lu-PSMA-617 (7.46 ± 0.15 GBq), patients underwent SPECT/CT at 3.2 ± 0.5, 23.9 ± 0.4, and 87.4 ± 12.0 h. Voxel-based dosimetry was performed with calibration factors (11.7 counts per second/MBq) and recovery coefficients derived from in-house phantom experiments. Lesions were segmented on baseline PSMA PET/CT (50% SUVmax). After a second cycle of [177Lu]Lu-PSMA-617 (44 ± 3 d; 7.50 ± 0.10 GBq) and an interim PSMA PET/CT scan, SBRT (27 Gy in 3 fractions) was delivered to all PSMA-avid oligometastatic sites, followed by post-PSMA PET/CT. RPT and SBRT voxelwise dose maps were scaled (α/β = 3 Gy; repair half-time, 1.5 h) to calculate the biologically effective dose (BED). Results: All patients completed the combination therapy without complications. No grade 3+ toxicities were noted. The median of the lesion SUVmax as measured on PSMA PET was 16.8 (interquartile range [IQR], 11.6) (baseline), 6.2 (IQR, 2.7) (interim), and 2.9 (IQR, 1.4) (post). PET-derived lesion volumes were 0.4-1.7 cm3 The median lesion-absorbed dose (AD) from the first cycle of [177Lu]Lu-PSMA-617 RPT (ADRPT) was 27.7 Gy (range, 8.3-58.2 Gy; corresponding to 3.7 Gy/GBq, range, 1.1-7.7 Gy/GBq), whereas the median lesion AD from SBRT was 28.1 Gy (range, 26.7-28.8 Gy). Spearman rank correlation, ρ, was 0.90 between the baseline lesion PET SUVmax and SPECT SUVmax (P = 0.005), 0.74 (P = 0.046) between the baseline PET SUVmax and the lesion ADRPT, and -0.81 (P = 0.022) between the lesion ADRPT and the percent change in PET SUVmax (baseline to interim). The median for the lesion BED from RPT and SBRT was 159 Gy (range, 124-219 Gy). ρ between the BED from RPT and SBRT and the percent change in PET SUVmax (baseline to post) was -0.88 (P = 0.007). Two cycles of [177Lu]Lu-PSMA-617 RPT contributed approximately 40% to the maximum BED from RPT and SBRT. Conclusion: Lesional dosimetry in patients with oligometastatic castration-sensitive prostate cancer undergoing [177Lu]Lu-PSMA-617 RPT followed by SBRT is feasible. Combined RPT and SBRT may provide an efficient method to maximize the delivery of meaningful doses to oligometastatic disease while addressing potential microscopic disease reservoirs and limiting the dose exposure to normal tissues.

Systemic therapy escalation after stereotactic body radiation therapy for oligometastatic hormone-sensitive prostate cancer

PurposeTo evaluate the oncological outcome after stereotactic body radiation therapy (SBRT) for oligometastatic hormone-sensitive prostate cancer (omHSPC) patients. Materials-MethodsIn this retrospective, observational, multi-institutional study, omHSPC patients (≤5 metastases) underwent SBRT. Primary endpoint was systemic therapy escalation-free survival (STE-FS) after SBRT. Local (LR), distant (DR), prostatic (PR) and isolated biochemical (iBR) relapses were reported with progression-free survival (PFS) and overall survival (OS). Prognostic factors for STE-FS were investigated. Toxicity was reported. ResultsFrom 01/07 to 09/19, 119 pts with omHSPC underwent SBRT. With a MFU of 34 months [12–97], median STE-FS was 33.4 months (95%CI 26.6–––40.1). Median OS was not reached and PFS was 22.7 months (CI95% 18.6–––32.3). Post-SBRT-PSA remained stable or decreased in 87 pts (73.1%). Progression events (LR, MR, PR, iBR) were observed in 72 pts (60.5%), among whom 6 relapsed in the irradiated area (local control rate: 95%). DR, BR, PR were observed in 44 pts (37%), 21pts (17.7%) and 2 pts (1.7%) respectively. In multivariate analysis, post-SBRT biochemical response was an independent prognostic factor for STE-FS. Grade ≥ 3 toxicity occurred in 1pt. ConclusionWith excellent local control and tolerance, SBRT for omHSPC patients represents an attractive approach to defer systemic therapeutic escalation and prevent its side effects. Accurate patient selection for SBRT requires more data with longer follow-up and higher numbers of patients pending the results of upcoming randomized trials.

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.

Stereotactic Body Radiotherapy for Lymph-Nodal Oligometastatic Prostate Cancer: A Multicenter Retrospective Experience.

Background: The favorable role of SBRT for lymph-nodal oligometastases from prostate cancer has been reported by several retrospective and prospective experiences, suggesting a more indolent natural history of disease when compared to patients with bone oligometastases. This retrospective multicenter study evaluates the outcomes of a cohort of patients treated with stereotactic body radiotherapy for lymph-nodal oligometastases. Methods: Inclusion criteria were up to five lymph-nodal oligometastases detected either with Choline-PET or PSMA-PET in patients naïve for ADT or already ongoing with systemic therapy and at least 6 Gy per fraction for SBRT. Only patients with exclusive lymph-nodal disease were included. The primary endpoint of the study was LC; a toxicity assessment was retrospectively performed following CTCAE v4.0. Results: A total of 100 lymph-nodal oligometastases in 69 patients have been treated with SBRT between April 2015 and November 2022. The median age was 73 years (range, 60-85). Oligometastatic disease was mainly detected with Choline-PET in 47 cases, while the remaining were diagnosed using PSMA-PET, with most of the patients treated to a single lymph-nodal metastasis (48/69 cases), two in 14 cases, and three in the remaining cases. The median PSA prior to SBRT was 1.35 ng/mL (range, 0.3-23.7 ng/mL). Patients received SBRT with a median total dose of 35 Gy (range, 30-40 Gy) in a median number of 5 (range, 3-6) fractions. With a median follow-up of 16 months (range, 7-59 months), our LC rates were 95.8% and 86.3% at 1 and 2 years. DPFS rates were 90.4% and 53.4%, respectively, at 1 and 2 years, with nine patients developing a sequential oligometastatic disease treated with a second course of SBRT. Polymetastatic disease-free survival (PMFS) at 1 and 2 years was 98% and 96%. Six patients needed ADT after SBRT for a median time of ADT-free survival of 15 months (range, 6-22 months). The median OS was 16 months (range, 7-59) with 1- and 2-year rates of both 98%. In multivariate analysis, higher LC rates and the use of PSMA-PET were related to improved DPFS rates, and OS was significantly related to a lower incidence of distant progression. No G3 or higher adverse events were reported. Conclusions: In our experience, lymph-nodal SBRT for oligometastatic prostate cancer is a safe and effective option for ADT delay with no severe toxicity.

Long-term outcomes of SBRT for PSMA PET detected oligometastatic prostate cancer

BackgroundOligometastatic disease in prostate cancer (PCa) is a challenging clinical scenario encountered more frequently with the widespread adoption of PSMA-PET. SBRT aims to defer androgen deprivation and may deliver sustained biochemical failure (BF) free survival in selected patients. Little long-term data is currently available regarding the effectiveness of this approach.MethodsA retrospective single institution study of PSMA-PET directed SBRT without initial ADT for oligo-metachronous PCa. Median dose/fractionation was 24 Gy in 2# to bones and 30 Gy in 3# to lymph nodes. The primary endpoint was time to BF (PSA + 0.2 ug/L above nadir). Secondary endpoints included time to ADT for relapse (i.e. palliative ADT), BF defined as PSA nadir + 2 ug/L, toxicity, patterns of failure and survival. Patients were excluded if they received ADT with their SBRT, had short disease-free interval, or > 3 metastases on PSMA-PET.Results103 patients treated from November-2014 to December-2019 were analysed from our prospective database. Median follow-up was 5 years. 64 patients were treated for nodal only disease, 35 bone only and 4 mixed. 15% were free of any BF at 5 years with median time to BF of 1.1 years. 32% (33/103) of patients had further curative-intent radiation treatment following their first BF after SBRT, including subsequent SBRT. Eight patients underwent potentially curative treatment for their second or third relapse. Allowing for salvage treatment, 29/103 (28%) were biochemically disease free at last follow up. At 5 years, 39% of patients had never received any ADT and 55% had not started ADT for relapse with a median time to ADT for relapse of 5.5 years. There were 2 grade 3 toxicities (rib fracture and lymphoedema), and no local failures.ConclusionPSMA-PET guided SBRT for oligo-metachronous PCa recurrence in appropriately triaged patients results in excellent local control, low toxicity and over 50% ADT free at 5 years.

Real-world evidence of outcomes of oligometastatic hormone-sensitive prostate cancer patients treated with metastasis-directed therapy.

To investigate characteristics and outcomes of oligometastatic hormone-sensitive prostate cancer (mHSPC) patients undergoing metastases-directed therapy (MDT) with external beam radiation therapy (EBRT). We relied on an institutional tertiary-care database to identify mHSPC patients who underwent EBRT as MDT between 12/2019 and 12/2022. Main outcomes consisted of progression to metastatic castration-resistant prostate cancer (mCRPC) and overall mortality (OM). Oligometastatic was defined as ≤3 metastases and bone and/or lymph node deposits were treated with conventional doses up to 54 Gy or with hypofractionated stereotactic regimes of median 24 Gy (20-27 Gy). Overall, 37 patients treated with EBRT as MDT were identified. The median follow-up was 13 months. Median age at MDT was 71 years and 84% exhibited ECOG performance status 0. The median baseline PSA at diagnosis was 10 ng/mL. Overall, primary local therapy consisted of radical prostatectomy (65%), followed by external beam radiation therapy to the prostate (11%), focal therapy (8%), and palliative transurethral resection of the prostate (5%). Overall, 32% exhibited de novo oligometastatic mHSPC. Bone metastases were present in 78% versus 19% lymph node metastases versus 3% both. The distribution of targeted oligo-metastases was 62% versus 38% for respectively one metastasis versus more than one metastasis. Androgen deprivation therapy (ADT) was combined with MDT in 84%. Moreover, 19% received combination therapy with apalutamide/enzalutamide and 12% with abiraterone or docetaxel. The median time to mCRPC was 50 months. In incidence analyses, 13% developed mCRPC after 24 months. OM after 24 months was 15% in mHSPC patients receiving MDT. Significant OM differences were observed after stratification into targeted metastatic burden (<0.05). No high-grade adverse events were recorded during MDT. Our real-world data suggest that MDT represents a safe treatment option for well-selected oligometastatic mHSPC patients.

The diagnosis and treatment of castrate-sensitive oligometastatic prostate cancer: A review.

Oligometastatic prostate cancer (OMPCa) is emerging as a transitional disease state between localized and polymetastatic disease. This review will assess the current knowledge of castrate-sensitive OMPCa. A review of the current literature was performed to summarize the definition and classification of OMPCa, assess the diagnostic methods and imaging modalities utilized, and to review the treatment options and outcomes. We further identify gaps in knowledge and areas for future research. Currently there is no unified definition of OMPCa. National guidelines mostly recommend systemic therapies without distinguishing oligometastatic and polymetastatic disease. Next generation imaging is more sensitive than conventional imaging and has led to early detection of metastases at initial diagnosis or recurrence. While mostly retrospective in nature, recent studies suggest that treatment (surgical or radiation) of the primary tumor and/or metastatic sites might delay initiation of androgen deprivation therapy while increasing survival in selected patients. Prospective data are required to better assess the incremental improvement in survival and quality of life achieved with various treatment strategies in patients with OMPCa.

Stereotactic Body Radiation Therapy Salvage for Lymph Node Recurrent Prostate Cancer in the Era of PSMA PET Imaging.

Our understanding of patterns of prostate cancer recurrence after primary treatment of localized disease has significantly evolved since the development of positron emission tomography (PET) agents targeting prostate cancer. Previously, most biochemical recurrences were not associated with imaging correlates when restaging with computed tomography (CT), magnetic resonance imaging (MRI), or bone scintigraphy and, hence, were typically assumed to represent occult metastases. A rising prostate specific antigen (PSA) after previous local therapy prompting a PET scan showing uptake limited to regional lymph nodes is an increasingly common clinical scenario as advanced prostate cancer imaging becomes more widely utilized. The optimal management strategy for patients who have lymph node recurrent prostate cancer is both unclear and evolving, particularly in terms of local and regionally directed therapies. Stereotactic body radiation therapy (SBRT) utilizes ablative radiation doses with steep gradients to achieve local tumor control while sparing nearby normal tissues. SBRT is an attractive therapeutic modality due to its efficacy, favorable toxicity profile, and flexibility to administer elective doses to areas of potential occult involvement. The purpose of this review is to briefly describe how SBRT is being implemented in the era of PSMA PET for the management of solely lymph node recurrent prostate cancer. SBRT has been shown to effectively control individual lymph node tumor deposits within the pelvis and retroperitoneum for prostate cancer and is well-tolerated with a favorable toxicity profile. However, a major limitation thus far has been the lack of prospective trials supporting the use of SBRT for oligometastatic nodal recurrent prostate cancer. As further trials are conducted, its exact role in the treatment paradigm of recurrent prostate cancer will be better established. Although PET-guided SBRT appears feasible and potentially beneficial, there is still considerable uncertainty about the use of elective nodal radiotherapy (ENRT) in patients with nodal recurrent oligometastatic prostate cancer. PSMA PET has undoubtedly advanced imaging of recurrent prostate cancer, revealing anatomic correlates for disease recurrence that previously went undetected. At the same time, SBRT continues to be explored in prostate cancer with feasibility, a favorable risk profile, and satisfactory oncologic outcomes. However, much of the existing literature comes from the pre-PSMA PET era and integration of this novel imaging approach has led to greater focus on new and ongoing clinical trials to rigorously evaluate this approach and compare to other established treatment modalities utilized for oligometastatic, nodal recurrence of prostate cancer.

Oligometastatic carcinoma prostate - An overview of the last decade.

Oligometastatic prostate cancer (OMPC) has gained profound interest lately due to its different tumor biology and our ability to use multimodality therapy for cure or prolonged survival. Selecting the appropriate patient for treatment has become the aim of treating urologists, medical oncologists, and radiation oncologists. Through this review, we try to highlight the management of OMPC in light of recent literature. Literature search was performed on Pubmed, Scopus and Embase using keywords "Oligometastatic", " Prostate Cancer" using operators such as "And" & "Or". Relevant articles were screened and all the latest articles on this emerging entity were included in this review. All trials relevant to oligometastatic prostate cancer defining the role of surgery, radiotherapy and systemic therapy were included and appropriate inferences were drawn. Relevant studies were compiled in tabular form for this article. The current standard of care of management for OMPC remains systemic therapy on the lines of hormone-sensitive metastatic prostate cancer. The evolving role of surgery, and radiotherapy along with systemic therapy is highlighted in this article.

Local Therapeutics for the Treatment of Oligo Metastatic Prostate Cancer.

Metastatic prostate cancer remains universally lethal. Although de-novo metastatic prostate cancer was historically managed with systemic therapy alone, local therapies are increasingly utilized in the early treatment of the disease, particularly in patients with oligometastatic prostate cancer (OMPC). OMPC represents an intermediate stage between clinically localized and widespread metastatic disease. Diseases classified within this stage present an opportunity for localized targeting of the disease prior to progression to widespread metastases. The purpose of this review is to discuss the contemporary and emerging local therapies for the treatment of OMPC. To date, there are three utilized forms of local therapy for OMPC: cryoablation, radiation therapy, and cytoreductive prostatectomy. Cryoablation can be utilized for the total ablation of the prostate and has shown promising results in patients with OMPC either in combination with ADT or with ADT and systemic chemotherapy. Radiation therapy along with ADT has demonstrated improvement in progression-free survival. The STAMPEDE Arm G, PEACE-1, and the HORRAD clinical trials have investigated radiation therapy for mPCa compared to standard of care versus systemic therapy with varying results. Cytoreductive radical prostatectomy (CRP) in conjunction with ADT has also been proposed in the management of OPMC with promising results from case-control and retrospective studies. Currently there are larger controlled trials investigating CRP for OPMC including the SIMCAP, LoMP, TRoMbone, SWOG 1802, IP2-ATLANTA, g-RAMPP, and FUSCC-OMPCa trials. Given the novel nature of local treatments for OPMC, treatment selection is still controversial and requires long-term follow-up and randomized clinical trials to aid patient and clinician decision making.

Oncological and perioperative outcomes of surgery with or without metastasis-directed therapy as part of a multimodal treatment in men with de-novo oligometastatic prostate cancer.

To investigate the feasibility, safety, and oncological outcomes of Radical Prostatectomy (RP; either Robot-Assisted [RARP] or Open RP [ORP]) in oligometastatic prostate cancer (omPCa). Additionally, we assessed whether there was an added benefit of metastasis-directed therapy (MDT) in these patients in the adjuvant setting. Overall, 68 patients with omPCa (≤ 5 skeletal lesions at conventional imaging) treated with RP and pelvic lymph node dissection between 2006 and 2022 were included. Additional therapies (androgen deprivation therapy [ADT] and MDT) were administered according to the treating physicians' judgment. MDT was defined as metastasis surgery/radiotherapy within 6months of RP. We assessed Clinical Progression (CP), Biochemical Recurrence (BCR), post-operative complications and overall mortality (OM) of RP and the impact of adjuvant MDT + ADT versus RP + ADT alone. Median follow-up was 73months (IQR 62-89). RARP reduced the risk of severe complications after adjusting for age and CCI (OR 0.15; p = 0.02). After RP, 68% patients were continent. Median 90-days PSA after RP was 0.12ng/dL. CP and OM-free survival at 7years were 50% and 79%, respectively. The 7-years OM-free survival rates were 93 vs. 75% for men treated with vs. without MDT (p = 0.04). At regression analyses, MDT after surgery was associated with a 70% decreased mortality rate (HR 0.27, p = 0.04). RP appeared to represent a safe and feasible option in omPCa. RARP reduced the risk of severe complications. Integrating MDT with surgery in the context of a multimodal treatment might improve survival in selected omPCa patients.

Treatment of Primary Tumor in Oligometastatic Prostate Cancer: An Observational Study of the Turkish Urooncology Association Prostate Diseases Working Group

Treatment of Primary Tumor in Oligometastatic Prostate Cancer: An Observational Study of the Turkish Urooncology Association Prostate Diseases Working Group

Oligometastatic Hormone-Sensitive Prostate Cancer. Why Radiotherapy?

Androgen deprivation therapy (ADT) has been considered for years the standard initial treatment for patients with metastatic prostate cancer (mPC). Recently published results support the use of taxanes, second-generation antiandrogens or radiotherapy to the primary tumor as part of the treatment in these patients, considering ADT alone as suboptimal. Metastasis-directed therapy (MDT) is used as part of the treatment for oligometastatic patients in different tumor types. In oligometastatic hormone-sensitive prostate cancer the role of MDT is being studied with promising results. In the present review we assess the available evidence for radiotherapy to the primary tumor in newly diagnosed mPC and for MDT in oligometastatic prostate cancer, as well as future directions in this clinical setting.

APPROACH trial: Multimodal approach in patients with mHSPC: A pragmatic, randomized, phase 3 trial of androgen-deprivation therapy (ADT) plus apalutamide (APA) versus ADT plus apalutamide (APA) and local treatment—Meet-URO 29 study.

TPS5115 Background: it is reasonable to offer radiotherapy (RT) to improve outcomes for patients with newly diagnosed M1 prostate cancer with &lt; 5 bone metastases (HORRAD) or low volume disease (STAMPEDE) (Burdett, S et al., Eur. Urol. 2019). Data from clinical randomized trials evaluating feasibility and overall benefit of cytoreductive radical prostatectomy (cRP) in oligometastatic ormone sensitive patients are not available. The rationale for performing cytoreductive radical prostatectomy is to eliminate lethal clones ofcastration-resistant intraprostatic PCa, which can favor the process of metastasis (A Heidenreich et al. Current Opinion in Urology 2020), in order to improve OS and PFS and to prevent local progression and correlated events. Methods: APPROACH is an Italian multicenter study, which is enrolling ~566 pts with oligometastatic hormone sensitive prostate cancer who are candidates to receive treatment with apalutamide. After 6 months from the start of treatment, patients will be randomized 1:1 to receive local treatment or not in addition to apalutamide (investigator's choice between primary radiotherapy and cytoreductive prostatectomy). Primary end point: To determine whether treatment with apalutamide plus ADT for 6 months followed by locoregional treatment with radiotherapy or radical prostatectomy has better efficacy than treatment with apalutamide plus ADT alone in terms of radiographic progression-free survival (rPFS). Secondary end points: To evaluate tumor shrinkage after locoregional approach and to evaluate short and long-term side effects after locoregional surgery or RT, time to PSA progression, time to castration resistance, cancer specific survival, overall survival and quality of life according to EPIC-26 and EQ-5D-5L questionnaires. Clinical trial information: NCT05649943 .

JU Open Plus: More AUA 2023 Annual Meeting Behind the Scenes

JU Open Plus: More AUA 2023 Annual Meeting Behind the Scenes

Sequential metastasis-directed therapy (MDT) for oligometastatic prostate cancer (Oligo PCa) assessed by PET-based imaging.

5032 Background: Prostate specific membrane antigen (PSMA) and F-18-Fluciclovine PET imaging have high sensitivity for the detection of prostate cancer (PCa) metastases. MDT with stereotactic body radiation therapy (SBRT) to PET-detected Oligo PCa has been shown to improve progression free survival (PFS) and delay androgen deprivation therapy (ADT). However, in those patients (pts) who ultimately develop oligoprogressive disease following MDT, the utility of subsequent courses of MDT has not been well defined. Methods: A single institution retrospective review was undertaken to describe outcomes following ≥2 courses of PET-guided SBRT in pts with Oligo PCa. Pts included in this analysis had undergone initial SBRT for ≤5 PCa lesions detected on PSMA or Fluciclovine PET, and subsequently underwent ≥1 additional course of SBRT at progression. Baseline data collected included stage, PSA level, Gleason Score, tracer type, and concurrent systemic therapy. Endpoints collected for each SBRT course included PSA decline ≥50% (PSA50), PFS, and systemic therapy change free survival (RxFS) (initiation of ADT, or for pts already on ADT, addition of an androgen signaling inhibitor). Association of factors with PFS after SBRT2 were analyzed using multivariable Cox proportional-hazards models. Results: 34 pts underwent ≥2 courses of MDT (SBRT1, SBRT2). At SBRT2, progression was identified by PSMA-PET in 26 (77%) pts, and by Fluciclovine-PET in 8 (23%). With SBRT2, 18 (53%) had a concurrent systemic therapy change; 10 (29%) did not receive any systemic therapy. 12 pts subsequently underwent SBRT3. Progression was detected by PSMA PET in 9 (75%) and Fluciclovine PET in 3 (25%). Clinical outcomes are summarized in the table. In the multivariable analysis, predictors associated with PFS following SBRT2 were 1) PSA decline at SBRT1 (HR 1.10, 95% CI 1.05-1.16, P&lt;0.001) and 2) PSA doubling time (PSADT) &lt; 12 months at the time of SBRT2 (HR 11.52, 95% CI 1.36-97.38, P 0.025). Overall, from SBRT1 to last follow-up (median 25.2 months), 23 (68%) pts remained ADT-free (14 after SBRT2; 9 after SBRT3). Conclusions: Serial MDT for Oligo PCa detected on PSMA or Fluciclovine PET is feasible and results in PSA declines, independent of change in systemic therapy. There is a persistent but diminishing benefit of MDT over successive courses. Overall, 2/3 of pts were able to postpone the use of ADT. PSA decline at SBRT1 and PSADT at SBRT2 may be biomarkers for SBRT2 benefit. Despite the retrospective nature of this study and cohort heterogeneity, these data provide a rationale for serial SBRT in Oligo PCA, and the need for larger, prospective studies of this strategy. [Table: see text]

The Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Oligometastatic Hormone-sensitive Prostate Cancer: A Post Hoc Analysis of ARCHES

BackgroundFew phase 3 studies have evaluated optimal systemic treatment strategies for patients with oligometastatic hormone-sensitive prostate cancer (HSPC), who may be at risk of undertreatment. ObjectiveTo evaluate outcomes for patients with oligometastatic and polymetastatic HSPC treated with enzalutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT. Design, setting, and participantsThis was a post hoc analysis of data for 927 patients with nonvisceral metastatic HSPC in the ARCHES trial (NCT02677896). InterventionPatients were randomized 1:1 to enzalutamide (160 mg/d orally) plus ADT or placebo plus ADT with HSPC categorized as oligometastatic (1–5 metastases) or polymetastatic (≥6 metastases). Outcome measurements and statistical analysisThe treatment effect on radiographic progression-free survival (rPFS), overall survival (OS), and secondary efficacy endpoints was evaluated in terms of the number of metastases. Safety was assessed. Cox proportional hazards models were used to generate hazard ratios (HRs). The Brookmeyer and Crowley method was used to generate 95% confidence intervals (CIs) for Kaplan-Meier median values. Results and limitationsEnzalutamide plus ADT improved rPFS (HR 0.27, 95% CI 0.16–0.46; p < 0.001), OS (HR 0.59, 95% CI 0.40–0.87; p < 0.005), and secondary endpoints in patients with oligometastatic or polymetastatic disease (rPFS: HR 0.33, 95% CI 0.23–0.46; p < 0.001; OS: HR 0.55, 95% CI 0.41–0.74; p < 0.001). Safety profiles were generally similar across subgroups. Limitations include the small numbers of patients with fewer than three metastases. ConclusionsThis post hoc analysis demonstrated the utility of enzalutamide, irrespective of metastatic burden or type of oligometastatic disease, and suggests that earlier treatment intensification with systemic potent androgen receptor inhibition is advantageous. Patient summaryThis study considered two treatment options for metastatic hormone-sensitive prostate cancer in patients with one to five metastases or six or more metastases. Treatment with enzalutamide plus ADT improved survival and other outcomes over ADT alone, whether patients had few or many metastases.

Clinical and Genomic Differences Between Advanced Molecular Imaging-detected and Conventional Imaging-detected Metachronous Oligometastatic Castration-sensitive Prostate Cancer

In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson’s χ2 test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. Patient summaryMetastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods.