Table 1.

Two or more arm trials assessing the oncologic efficacy of cytoreductive radical prostatectomy in (oligo-)metastatic prostate cancer

Study	Identifier	N°	Setting	BST/SOC/SST	BST/SOC/SST before randomization/intervention	Inclusion criteria	Definition of (oligo-)metastasis	Primary endpoints	Secondary endpoints	Status
Phase II Trial on Best Systemic Therapy or Best Systemic Therapy (BST) Plus Definitive Treatment (Radiation or Surgery) of the Primary Tumor in Metastatic (M1) Prostate Cancer	NCT01751438	180	•BST versus •BST + CRP/RT to the prostate	NR	6 months (±14 days)	•Histologically or cytologically proven PCa •Castration sensitive •ECOG PS 0 or 1 •Life expectancy >2 years	M1 disease by AJCC staging by bone scan, CT, and/or MRI	PFS	NR	Active, not recruiting
SWOG 1802: Phase III Randomized Trial of Standard Systemic Therapy (SST) Versus Standard Systemic Therapy Plus Definitive Treatment (Surgery or Radiation) of the Primary Tumor in Metastatic Prostate Cancer	NCT03678025	1273	•SST versus •SST + CRP/RT to the prostate (± MDRT)	Abiraterone, bicalutamide, degarelix, flutamide, goserelin acetate, histrelin acetate, leuprolide acetate, nilutamide, orchiectomy, triptorelin	22-28 weeks	•Histologically or cytologically proven PCa (adeno) •Castration sensitive •MDRT for up to four sites if completed before randomization	•M1 disease by bone scan, CT, or MRI •Metastatic disease on PET scan only but not conventional imaging or solitary metastases by conventional imaging must be confirmed histologically or cytologically	OS	•OS in SST + CRP versus SST alone in the subset who specify the surgical intent stratification factor •Rate of symptomatic local progression •PFS •PFS in the subsets of patients ± MDRT to oligometastatic sites	Recruiting
SIMCAP: Phase 2.5 Multi-Institution Randomized Prospective Clinical Trial Evaluating the Impact of Cytoreductive Radical Prostatectomy Combined With Best Systemic Therapy on Oncologic and Quality of Life Outcomes in Men With Newly Diagnosed Metastatic Prostate Cancer	NCT03456843	190	•BST versus •BST + CRP	ADT ± docetaxel	≥1 month	•Histologically or cytologically proven PCa (adeno) •Castration sensitive •ECOG PS 0 or 1	•M1(a-c) disease by bone scan, CT, MRI, or histological confirmation •If solitary lesion, metastasis confirmed with biopsy or two independent imaging modalities (CT, PET, bone scan, or MRI)	•FFS (PSA progression, clinical progression, radiographic progression, or death from prostate cancer) •In phase III OSa	In phase II: •OS •CSS •Overall complication rate •Time to biochemical progression	Recruiting
IP2-ATLANTA: Phase II Trial on Additional Treatments to the Local Tumour for Metastatic Prostate Cancer: Assessment of Novel Treatment Algorithms	NCT03763253	•918 •25 (PSMA-PET substudy)	•SST versus •CRP/RT + SST (+ MDT) versus •MIAT (HIFU/cryotherapy) + SST (+ MDT) •PSMA-PET/CT substudy	•ADT ± docetaxel or other systemic/local directed treatment including abiraterone or enzalutamide •RT defined as palliative/cytoreductive in high-volume metastases or to mirror STAMPEDE local RT arm in low-volume metastases	≤3 months	•Histologically proven PCa •Castration sensitive •ECOG PS 0-2	Metastatic disease (any T, any N, M1+) of any grade, stage, or PSA level	•PFS (composite outcome) •PSMA-PET substudy: diagnostic accuracy regarding detection of residual disease	•Several QOL measures •Progression on PSA and imaging •Cost-effectiveness	Recruiting
LoMP II: Phase II trial on Local Treatment With Radical Prostatectomy (RP) for Newly-diagnosed Metastatic Prostate Cancer (mPCa)	NCT03655886	86	•SST + CRP versus •SST + RT to the prostate bed and pelvis	NR	NR	•Histologically proven PCa •Castration sensitive •ECOG PS 0-2 (2 if related to local PCa symptoms)	Newly diagnosed M1 disease by CT or bone scan	Feasibility of randomization at 48 months	CRPC-free survival	Recruiting
FUSCC-OMPCa: An Open-label, Randomized Prospective Phase II Trial of Androgen Deprivation Therapy or Androgen Deprivation Therapy Plus Definitive Treatment (Radiation or Surgery) of the Primary Tumor in Oligometastatic Prostate Cancer	NCT02742675	200	•ADT versus •ADT + CRP/RT to the prostate	Bicalutamide, goserelin acetate, flutamide, leuprolide acetate, triptorelin	NR	•Histologically proven PCa •Age between 18 and 80 years •Castration sensitive •ECOG PS 0-2 (2 if related to local PCa symptoms)	•M1 disease by AJCC staging by bone scan, CT, and/or MRI •Metastatic lesions limited to the lymph nodes or bones (number of lesions ≤5)	PFS	•OS •Time to PSA progression •QOL	Active, not recruiting
Testing Radical Prostatectomy in Chinese Men With Prostate Cancer and oligoMetastases to the Bone	NCT03988686	120	•SOC versus •SOC + CRP	ADT ± other systemic therapies based on current guidelines	NR	•Histologically proven PCa •Age between 19 and 75 years •Castration sensitive •ECOG PS 0-1	•1-3 skeletal lesions on bone-specific imaging •No visceral metastases	Time to CRPC	QOL	Unknown
A Randomized, Controlled, Multi-Center Clinical Trial to Evaluate the Efficacy and Safety of Prostatectomy for Castration-Naive Oligometastatic Prostate Cancer	NCT04992026	128	•SOC versus •SOC + CRP	ADT plus abiraterone	<9 months	•Histologically proven PCa •Age ≥40 and ≤75 years •Castration sensitive •ECOG PS 0-1 •PSA <2 ng/ml before enrollment •Testosterone level of <50 ng/dl or <1.7 nmol/l during treatment for patients previously treated with surgical castration or ADT •Treatment with ≥6 cycles of abiraterone	•≤5 metastatic lesions •No visceral metastasis •Diameter of a single lesion ≤5 cm or surface area ≤250 cm2	•Time to PSA progression •Time to radiographic progression	•Radiographic PFS •Time to CRPC •Time to PSA remission (≥50%) and time to PSA remission (≥90%) •Time to new anticancer treatment	Recruiting

ADT, androgen deprivation therapy; AJCC, American Joint Committee on Cancer; BST, best systemic therapy; CRP, cytoreductive radical prostatectomy; CRPC, castration-resistant prostate cancer; CSS, cancer-specific survival; CT, computed tomography; ECOG PS, Eastern Cooperative Oncology Group performance status; FFS, failure-free survival; HIFU, high-intensity focal ultrasound; LoMP, Local Treatment for Metastatic Prostate Cancer; MDRT, metastasis-directed radiotherapy; MDT, metastasis-directed treatment; MIAT, minimally invasive ablative therapy; MRI, magnetic resonance imaging; NR, not reported; OMPCa, oligometastatic prostate cancer; OS, overall survival; PCa, prostate cancer; PET, positron emission tomography; PFS progression-free survival; PSA, prostate-specific antigen; PSMA, prostate-specific membrane antigen; QOL, quality of life; RT, radiotherapy; SIMCAP, Surgery in Metastatic Carcinoma of Prostate; SOC, standard of care; SST, standard systemic therapy; SWOG, Southwest Oncology Group.

^aIf FFS in the control arm improved by ≥30% at 2 years after randomization, a phase III study will start and OS will be the primary endpoint.