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

Skin and Connective Tissue Diseases

Rare Diseases

Neoplasm Metastasis

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Hematinics

Immunomodulating Agents

Liver Extracts

Immunologic Factors

Patients randomised to the interventional study arm, receiving both surgical metastasectomy and continued immunotherapy. Each patient case will be individually planned for surgery. Procedures will include, but will not be limited to, lung resections, liver resections, bowel resection, skin excisions and lymph node clearances. Patients in both study arms will continue with PD-1 inhibitor 12 months after randomization, and will then be treated according to their medical oncologist.

Patients randomized to control study arm, receiving continued immunotherapy only. Patients in both study arms will continue with PD-1 inhibitor 12 months after randomization, and will then be treated according to their medical oncologist.

Surgical removal of metastases aimed at R0 resection.

Continued PD1-inhibitor treatment according to current treatment standards.

Immunotherapy

To evaluate if surgical removal of residual disease adds benefit in stage IV melanoma patients with partial response or stable disease after a minimum 9 months of first-line PD-1 inhibition. Primary endpoint: Disease-free survival (DFS) at 12 months.

A Phase II Randomized Controlled Open-Label Parallel Group Interventional Multicenter Trial. Patients with metastatic melanoma, stratified for stage M1a or M1b/M1c, that have received first-line treatment with PD-1 inhibitors for a minimum of 9 months resulting in either partial response or stable disease according to RECIST 1.1 will be eligible. Patients will be screened for operability based on CT-scans examined by a multidisciplinary team, with the criteria that complete (R0) resection of all metastases should be possible. If the multidisciplinary team find that this would be possible, patients will be included and randomized 1:1 to either surgery with continued PD1-inhibition or current standard of care with continued PD1-inhibition only. At progression, treatment will be according to the treating medical oncologist. Active follow-up will be performed for 12 months.

A Phase II Randomized Controlled Open-Label Parallel Group Interventional Multicenter Trial

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
Surgery of Melanoma Metastases After Systemic Therapy	NCT04242329	Melanoma Melanoma Stage ... Metastatic Mela... Surgery	Surgical metast... Immunotherapy	18 Years -	Vastra Gotaland Region
Surgery of Melanoma Metastases After Systemic Therapy	NCT04242329	Melanoma Melanoma Stage ... Metastatic Mela... Surgery	Surgical metast... Immunotherapy	18 Years -	Vastra Gotaland Region

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