Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Androgens

Abiraterone Acetate

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Hormones

Hormone Antagonists

Cytochrome P-450 Enzyme Inhibitors

Removal of the prostate and seminal vesicles.

Radical prostatectomy

Prostate irradiation

Surgical metastasectomy

Irradiation of metastases

Administered as part of multimodal treatment for oligometastatic prostate cancer

Abiraterone acetate

Enzalutamide

Darolutamide

Apalutamide

Lutetium-PSMA

Androgen deprivation treatment

Tamás Fazekas, MD

Pawel G Rajwa, MD PhD

Shahrokh F Shariat, MD PhD DDsc

PSMA-PET/CT or PSMA-PET/MRI are more accurate imaging modalities compared to CT/BS; in approximately 10-20% of high-risk patients diagnosed using conventional imaging PSMA-PET up-stages the disease. Therefore a substantial proportion of high-risk patients previously considered as non-metastatic are expected to be diagnosed with oligometastatic disease. While standard treatment pathways exist for patients with non-metastatic or oligometastatic disease confirmed using conventional imaging, less is known about the optimal management of patients with oligometastatic prostate cancer on PSMA-PET.

Currently, data on the safety, effectiveness and oncologic outcomes of local therapies in oligometastatic patients diagnosed using PSMA-PET have been poorly reported so far. Thus, there is a need for a prospectively maintained database to collect real-world clinical data to produce high-quality research on the optimal management in oligometastatic prostate cancer who underwent PSMA-PET for primary staging and subsequent local therapy. This database will allow centers to retro- and prospectively collect data to facilitate analysis and assessment of the outcomes of oligometastatic patients managed with local therapy.

The Emerging Role of PSMA-PET in Prostate Cancer Imaging

PSMA-PET, in conjunction with CT or MRI, has significantly enhanced the precision of prostate cancer staging. Traditional imaging modalities, such as CT or BS, often fail to accurately determine the disease's extent. In contrast, PSMA-PET offers a more precise diagnostic alternative, especially in identifying oligometastatic cases among high-risk prostate cancer patients. Remarkably, 10-20% of patients with unfavorable prostate cancer initially classified as non-metastatic through conventional imaging are reclassified as oligometastatic when reassessed with PSMA-PET. This reclassification is pivotal, possibly influencing treatment decisions and prognostic outcomes.

The Need for a Focused Study

Oligometastatic prostate cancer represents an intermediate stage between localized and systemic disease, reflecting an early phase in metastatic progression. These tumors not only exhibit unique biological characteristics but also constitute a distinct clinical entity, offering possibilities for long-term control or even cure. Numerous studies demonstrated benefits from combining local and metastasis-directed therapies with systemic treatment in oligometastatic prostate cancer patients diagnosed with conventional imaging. However, despite diagnostic advancements and the evolving uptake of PSMA-PET, substantial gaps persist in the understanding of optimal management for oligometastatic prostate cancer identified with next-generation imaging.

Due to the diagnostics advancements and dynamically changing treatment landscape with various local, systemic, and metastasis-directed therapies, this topic requires a prospective multicenter registry. To address this, the investigators have initiated this prospective cohort study focusing on the efficacy and safety of local therapies in oligometastatic prostate cancer patients diagnosed with PSMA-PET, performed under the umbrella of EAU Young Academic Urologists (YAU) Prostate Cancer Working Group.

Study Design and Objectives

This multicenter, prospective observational cohort study aims primarily to evaluate time to castration-resistance, clinical and radiological progression-free survival in patients with oligometastatic prostate cancer identified using PSMA-PET. Secondary objectives include assessing complications of local therapies, pathological, functional, and oncologic outcomes among others.

Eligible patients are those diagnosed with primary oligometastatic prostate cancer with PSMA-PET and treated with local therapies such as radical prostatectomy or radiation. The oligometastatic state is defined as cM1a and/or cM1b with ≤5 bone metastases and/or M1c with ≤3 lung lesions, with or without cN positivity. Key exclusion criteria include the presence of visceral metastases (other than lungs) or neoadjuvant therapy before initial PSMA-PET assessment.

The study aims to answer pivotal questions about oncological, functional, and safety outcomes after local treatment in oligometastatic prostate cancer patients on PSMA-PET. Furthermore, the goal is to report treatment strategies for this disease state in this dynamically changing field, and to identify factors predicting improved outcomes.

Data Collection and Management

Data will be meticulously collected and managed using the Castor electronic case report form platform, provided by the European Association of Urology Foundation for Urological Research, ensuring pseudonymization and security. With the study starting in 2024, the investigators aim to collect data until end of 2030.

Estimated Impact of the Study

This study is anticipated to substantially contribute to the understanding of oligometastatic prostate cancer and the role of PSMA-PET in its diagnosis and management. In a recent multicenter EAU-YAU study closely related to OLIGOMET project, the investigators have shown that patients with oligometastatic prostate cancer diagnosed with PSMA-PET and treated with radical prostatectomy have overall favorable oncologic outcomes. Nevertheless, a portion of these patients still faced a risk of early progression, emphasizing the need for multimodal therapy. The study illustrated the lack of evidence and precise clinical guidance in this distinct disease stage; there existed significant heterogeneity in the treatment approach among participating tertiary referral centers, with the majority of patients receiving multimodal therapy.

While the combination of radiation and systemic therapy can be considered the current standard of care in oligometastatic patients on conventional imaging, the preferred management of patients with a small metastatic burden on PSMA-PET remains unknown. Therefore, the investigators believe that evaluating the effectiveness of local therapies in patients diagnosed with next-generation imaging can pave the way for personalized, and effective treatment strategies of oligometastatic disease in the future. Moreover, the use of PSMA-PET may allow for early identification and intervention, potentially altering the natural history of the disease and improving oncologic control. Finally, the investigators expect that by understanding the role of combination therapies and identifying predictive factors to guide treatment selection, could lead to extended survival and improved quality of life of patients.

Outcomes of Local Treatment for Oligometastatic Prostate Cancer Diagnosed Using PSMA PET Imaging: OLIGOMET Study

Defined as increase in size of existing lesion or appearance of new lesion (on any subsequent follow-up imaging modality used for baseline assessment), or death.

Defined as new prostate cancer-related symptom, radiographic progression, initiation of new treatment, or death.

Castration resistance is defined as: castrate serum testosterone \<50ng/dL or 1.7nmol/L, plus either biochemical progression (three consecutive rises in PSA at least one week apart resulting in two 50% increases over the nadir, and a PSA \> 2ng/mL) or radiographic progression (\> 2 new bone lesions or a new soft tissue lesion).

Local therapy complications are assessed using Clavien-Dindo classification for radical prostatectomy and RTOG/EORTC Radiation Toxicity Grading for radiation therapy.

Defined as prostate cancer downstaging and/or decrease in number of metastasis lesions due to the effect of systemic therapy.

Time Frame:

Measured from the administration of systemic treatment until the end of treatment, assessed up to 100 months

Defined as continence rate (no incontinence 0 pads/24h, mild 1 pads/24h, moderate 2-3 pads/24h, severe \>3 pads/24h).

Defined as potency (potent ( IIEF-EF=\>22), inpotent (IIEF-EF \<22)

Time from oligometastasis diagnosis to death from prostate cancer.

Time from oligometastasis diagnosis to death of any cause.

IRCCS Ospedale San Raffaele

University Hospital of Cologne

St. Antonius Hospital

Istituto Europeo di Oncologia

University Hospital, Udine, Italy

Azienda Ospedaliera San Giovanni Battista

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice

Lund University

Medical University of Warsaw

Ziekenhuis Netwerk Antwerpen (ZNA)

Medical University of Vienna

Principal Investigator

Symptoms and General Pathology

Neoplasm Metastasis

Nootropic Agents

Gastrointestinal Agents

Lipid Regulating Agents

Vitamins

Choline

The participants will undergo two project scans: WB-MRI and SPECT-CT

The participants will undergo two project scans: WB-MRI and Cholin-PET-CT

The participants will undergo two project scans: WB-MRI and PSMA-PET-CT

WB-MRI

SPECT-CT

Cholin-PET-CT

PSMA-PET-CT

Eva Dyrberg Mortensen, MD

Henrik S. Thomsen, Professor

Henrik S Thomsen, Professor

An improved diagnosis of bone metastases in prostate cancer patients can have a significant impact on treatment strategy and probably survival as well.

The primary purpose of the project is to determine the diagnostic accuracy of bone SPECT-CT, choline-PET-CT, PSMA-PET-CT, NaF-PET-CT and Whole-body MRI in the diagnosis of bone metastases in prostate cancer patients.

The project is a prospective diagnostic test accuracy study. The project takes place at Herlev Hospital and is a collaboration between the Department of Radiology and the Department of Clinical Physiology and Nuclear Medicine.

The investigators want to include 300 prostate cancer patients referred to our standard diagnostic imaging (NaF-PET-CT scan) by the clinicians.

In addition to the standard diagnostic imaging (NaF-PET-CT-scan), two project will be performed on all participants. The project has three arms with the following scanning combinations:

A) Whole-body MRI + SPECT-CT B) Whole-body MRI + Cholin-PET-CT C) Whole-body MRI + PSMA-PET-CT The recruitment of project participants takes place on the day when the patients are undergoing a NaF-PET-CT scan in the course of regular clinical practice at our institution.

All readers are experienced radiologists or specialists in nuclear medicine. Patient identification on each scan will be anonymized and the reader will not have access to clinical and biochemical information or previous imaging studies.

Study participants will be allocated to the "ongoing project arm" at the time of enrollment.

Diagnostic Imaging of Bone Metastases in Prostate Cancer Patients

A Prospective Study Comparing the Diagnostic Accuracy of Bone SPECT-CT, Choline-PET-CT, PSMA-PET-CT, NaF-PET-CT and WB-MRI in the Detection of Prostate Cancer Bone Metastases

Herlev Hospital

MD, Phd-student

Bone Density Conservation Agents

Etidronic Acid

Radium Ra 223 dichloride

Radium-223-chloride 50kBg/kg, every 4 weeks intravenously, for a total of 6 administrations.

Rhenium-188-HEDP 40MBq/kg, every 8 weeks intravenously, for a total of 3 administrations.

Intravenously 50 kBq/kg every 4 weeks. Total: 6 administrations

Radium-223 chloride

Intravenously 40 MBq/kg every 8 weeks. Total: 3 administrations

Rhenium-188-HEDP

Alfons JM van den Eertwegh, Prof.dr.

Radium-223 chloride is an alpha-emitting radiopharmaceutical with proven survival benefit in patients with castration-resistant prostate cancer metastatic to bone. Beta-emitting radiopharmaceuticals have proven efficacy for palliating malignant bone pain. Nowadays, rhenium-188-HEDP is used in clinical practice for pain relief and palliative care. Several studies suggest that also rhenium-188-HEDP has the potential to improve overall survival. The purpose of this study is to investigate if treatment with rhenium-188-HEDP results in improvement of overall survival compared to treatment with radium-223-chloride.

The main objective of this trial is to compare rhenium-188-HEDP (a beta-emitting radiopharmaceutical) with radium-223-chloride (an alfa-emitting radiopharmaceutical), in patients with castration-resistant prostate cancer metastatic to bone, with overall survival as primary endpoint.

For radium-223-chloride, an overall survival benefit has been proven in a large randomized phase III trial. Although such a trial has never been performed for rhenium-188-HEDP, some trials in literature suggest a survival benefit for rhenium as well.

Rhenium has some advantages compared to radium. Firstly, it is easily available as it can be produced in the hospital. Secondly, the costs of rhenium are significantly lower compared to radium. Lastly, rhenium seems to have a favorable pain response. However, no randomized trials have been performed to confirm this.

Patients will be randomized between

* radium-223-chloride intravenously, for a total of 6 administrations (every 4weeks)
* rhenium-188-HEDP intravenously for a total of 3 administratrions (every 8 weeks)

Rhenium-188-HEDP vs. Radium-223-chloride in Patients With Advanced Prostate Cancer Refractory to Hormonal Therapy

Repeated Rhenium-188-HEDP Versus Radium-223-chloride in Patients With Metastatic Castration-resistant Prostate Cancer: The RaRe Study

Time from randomization until death due to any cause,

Time from randomization to the date of a minimum of rising PSA levels with an interval of \>1week between each determination

Time from randomization to the date of earliest objective evidence of ALP progression.

Time from randomization to the date of first clinical progression.

Time from randomization to the date of first skeletal related events

Measured by the EORTC quality of Life Questionnaire C30

Ratio between the difference in costs and the difference in benefits (quality of life of treatment with rhenium-188-HEDP of radium-223-chloride)

Amsterdam UMC, location VUmc

Radium Ra 223 dichloride will be delivered intravenously at 55 kBq/kg (1.49 mCi)/kg (+/- 10% total dose) for a total of six cycles. 1 cycle= 28 days. The first cycle will commence at study enrollment, then cycles 2-6 will commence after the completion of radiotherapies at 4 week intervals

Radium Ra 223 Dichloride

All external beam radiations oligometastatic sites will commence after cycle 1 of Radium-223 but prior to cycle 2 of Radium-223. All subjects will receive Stereotactic body or hypofractionated radiation to sites of bone disease seen on imaging studies. Patients will have the primary tumor sites and 5 or fewer sites of bone-only metastasis treated with external beam radiation.

Any of the following regimens are considered ablative, acceptable and are biologically equivalent to 60Gy EQD2:

* Single fraction: 16 Gy total at 16 Gy per fraction (SBRT)
* Three fractions: 24 Gy total at 8 Gy per fraction (SBRT)
* Five fractions: 30 Gy total at 6Gy per fraction (SBRT).When using five fractions, can reduce to 25 Gy total at 5 Gy per fraction (SBRT) or to a minimum of 20 Gy total at 4 Gy per fraction (SBRT), per treating investigator.
* Six fractions: 32.4 Gy total at 5.4Gy per fraction (Hypofractionated)

Radiation

This is a phase IIa, open label, single arm, and prospective study of hormone therapy-naïve men with oligometastatic prostate cancer to the bone. The study will test if treating the primary tumor sites and 5 or fewer sites of bone-only metastasis with external beam radiation with concomitant systemic Radium-223 will reduce the utilization of androgen deprivation therapy, improve QOL and improve OS over a the comparator cohort of SWOG intermittent ADT historic cohort.

This is a phase IIa, open label, single arm, prospective study

Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone

A Phase 2 Study of Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone

To determine if 20% of ADT naïve men treated with concurrent EBRT and Radium-223 will not require ADT for progression by 15 months.

Determine the hormone-therapy free survival time for men treated with concurrent EBRT and Radium-223 and determine if it is a 30% risk reduction over the SWOG intermittent ADT historic cohort

To evaluate health related quality of life (QOL) as scored by the 50 item Expanded Prostate Inventory Composite (EPIC) EPIC urinary, bowel, sexual and hormonal domains.

EPIC assesses the disease-specific aspects of prostate cancer and its therapies and comprises four summary domains (Urinary, Bowel, Sexual and Hormonal). Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health-related quality of life.

To evaluate health related quality of life (QOL). The PROMIS-29 (Patient-Reported Outcomes Measurement Information System) will be used to assess general function and well-being.

The raw score for each PROMIS instrument is converted to a T-score on a scale of 0-100. For most PROMIS instruments, a score of 50 is the average for the United States general population with a standard deviation of 10. A higher PROMIS T score represents more of the concept being measured. For negatively worded concepts like Anxiety, a T score of 60 is one SD worse than average. By comparison, an Anxiety T score of 40 is one SD better than average. However, for positively worded concepts like Physical Function Mobility, a T score of 60 is one SD better than average while a T score of 40 is one SD worse than average.

Documentation of complications associated with bone metastases and may include (but not limited to) fractures, spinal cord compression, bone pain, and hypercalcemia.

Time elapsed from baseline PSA to double in value.

Evaluate overall survival at 2 years relative to the SWOG intermittent ADT historic cohort.

Endpoint: Patients will be followed for survival for two years after study enrollment

Bayer

University of Utah

Radium Ra 223 Dichloride: Radium Ra 223 dichloride will be delivered intravenously at 55 kBq/kg (1.49 mCi)/kg (+/- 10% total dose) for a total of six cycles. 1 cycle= 28 days. The first cycle will commence at study enrollment, then cycles 2-6 will commence after the completion of radiotherapies at 4 week intervals

Radiation: All external beam radiations oligometastatic sites will commence after cycle 1 of Radium-223 but prior to cycle 2 of Radium-223. All subjects will receive Stereotactic body or hypofractionated radiation to sites of bone disease seen on imaging studies. Patients will have the primary tumor sites and 5 or fewer sites of bone-only metastasis treated with external beam radiation.

Any of the following regimens are considered ablative, acceptable and are biologically equivalent to 60Gy EQD2:

* Single fraction: 16 Gy total at 16 Gy per fraction (SBRT)
* Three fractions: 24 Gy total at 8 Gy per fraction (SBRT)
* Five fractions: 30 Gy total at 6Gy per fraction (SBRT).When using five fractions, can reduce to 25 Gy total at 5 Gy per fraction (SBRT) or to a minimum of 20 Gy total at 4 Gy per fraction (SBRT), per treating investigator.
* Six fractions: 32.4 Gy total at 5.4Gy per fraction (Hypofractionated)

Radium Ra 223 Dichloride and Radiation, All Patients

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Clinicaltrials.gov and CTRP Specialist

Count of Participants Requiring Androgen Deprivation Therapy (ADT) Use at 15 Months

8 of 20 total patients did not begin ADT while on study, so 12 of 20 patients were evaluated for this measure

Median Time From Start of Study Therapy to Start of ADT

Urinary Summary Score

Bowel Summary Score

Sexual Summary Score

Hormonal Summary Score

Of the 20 total participants, 10 completed the EPIC questionnaire at the End of Treatment timepoint

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Outcomes of Local Treatment for Oligometastatic Prostate Cancer Diagnosed Using PSMA PET Imaging: OLIGOMET Study	NCT06430411	Prostate Cancer... Prostate Cancer... Prostate Cancer Prostate Neopla... Oligometastatic... Oligometastasis	Radical prostat... Prostate irradi... Surgical metast... Irradiation of ... Abiraterone ace... Enzalutamide Darolutamide Apalutamide Docetaxel Lutetium-PSMA Androgen depriv...	18 Years - 80 Years	Medical University of Vienna
Outcomes of Local Treatment for Oligometastatic Prostate Cancer Diagnosed Using PSMA PET Imaging: OLIGOMET Study	NCT06430411	Prostate Cancer... Prostate Cancer... Prostate Cancer Prostate Neopla... Oligometastatic... Oligometastasis	Radical prostat... Prostate irradi... Surgical metast... Irradiation of ... Abiraterone ace... Enzalutamide Darolutamide Apalutamide Docetaxel Lutetium-PSMA Androgen depriv...	18 Years - 80 Years	Medical University of Vienna
Diagnostic Imaging of Bone Metastases in Prostate Cancer Patients	NCT03134261	Prostate Cancer...	WB-MRI SPECT-CT Cholin-PET-CT PSMA-PET-CT	18 Years -	Herlev Hospital
Diagnostic Imaging of Bone Metastases in Prostate Cancer Patients	NCT03134261	Prostate Cancer...	WB-MRI SPECT-CT Cholin-PET-CT PSMA-PET-CT	18 Years -	Herlev Hospital
Rhenium-188-HEDP vs. Radium-223-chloride in Patients With Advanced Prostate Cancer Refractory to Hormonal Therapy	NCT03458559	Prostate Cancer...	Radium-223 chlo... Rhenium-188-HED...	18 Years -	Amsterdam UMC, location VUmc
Radium-223 and Radiotherapy in Hormone-Naïve Men With Oligometastatic Prostate Cancer to Bone	NCT03304418	Prostate Cancer...	Radium Ra 223 D... Radiation	18 Years -	University of Utah

Spots Global Cancer Trial Database for prostate cancer metastatic to bone