PEACE V: Salvage Treatment of OligoRecurrent Nodal Prostate Cancer Metastases (STORM)

Ghent University Hospital (UZ)

Status and phase: Active, not recruiting; Phase 2

Conditions: Metastatic Cancer; Oligometastatic Cancer; Prostate Cancer Metastatic; Prostate Cancer

Treatments: Procedure: salvage Lymph Node Dissection; Radiation: whole pelvic radiotherapy; Radiation: metastasis-directed treatment; Drug: androgen deprivation therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT03569241

EC/2018/0130

Details and patient eligibility

About

A proportion of prostate cancer (PCa) patients develop relapse following curative local treatment. Regional nodal recurrence is an emerging clinical situation since the introduction of new molecular imaging methods in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of progression, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.

The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (salvage lymph node dissection, sLND or stereotactic body radiotherapy, SBRT) or MDT plus whole pelvis radiotherapy (WPRT: 45 Gy in 25 fractions).

Full description

A proportion of prostate cancer (PCa) patients develop a local, regional (N1) or distant (M1) relapse following curative local treatment. For both local and distant relapses, different treatment recommendations are made in the guidelines (EAU guidelines 2016). However, the entity regional nodal recurrence is not mentioned in the guidelines but is an emerging clinical situation since the introduction of choline and more recently PSMA PET-CT in the restaging of recurrent prostate cancer. More specifically, a subgroup of these patients is being diagnosed with a recurrence confined to the regional lymph nodes and limited in number (oligorecurrence) using choline or PSMA PET-CT. As there are no specific treatment recommendations for these type of patients, different treatment approaches are currently used, mostly focusing on local ablative treatments using radiotherapy or surgery. These treatments are coined metastasisdirected therapy (MDT). MDT in combination with or without temporary ADT could delay the subsequent risk of metastases, and even cure limited regional nodal recurrences. Consequently, lifelong palliative ADT, with its toxicity and excess in non-cancer mortality might be postponed.

The proposed trial randomizes patients with oligorecurrent nodal prostate cancer following primary PCa treatment to either metastasis-directed therapy (MDT) (sLND or SBRT) or MDT plus WPRT. In the recurrent PCa setting, 2 recent trials have suggested a progression-free and even survival benefit of adding temporary ADT to local salvage prostate bed radiotherapy. Consequently, this positive effect might also be applicable for regional recurrences. Although the optimal duration of ADT is unknown, a minimal duration of 6 months of ADT seems advisable in this setting and will be mandatory for both arms.

This trial will improve our insights in the pattern of recurrence following these treatment modalities with the expectation that WPRT will reduce the number of nodal relapses, improving metastasis-free survival and postponing the need for palliative systemic treatments while maintaining quality-of-life. The current phase II trial will try to establish a golden standard in the treatment of oligorecurrent nodal PCa.

Enrollment: 196 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically proven initial diagnosis of adenocarcinoma of the prostate
• Biochemical relapse of prostate cancer following radical local prostate treatment (radical prostatectomy, primary radiotherapy or radical prostatectomy +/- prostate bed adjuvant/ salvage radiotherapy) according to the EAU guidelines 2016.
• Following radical prostatectomy, patients with a biochemical relapse are eligible in case a nodal relapse is detected in the pelvis even in the absence of prior postoperative prostate bed radiotherapy (adjuvant or salvage).
• In case of a suspected local recurrence following primary radiotherapy, a biopsy should confirm local recurrence and patients with a confirmed local recurrence are eligible in case they also undergo a local salvage therapy. If imaging rules out local relapse, patients are eligible.
• Nodal relapse in the pelvis on choline, PSMA or FACBC PET-CT with a maximum of 3 positive nodal lymph nodes. The upper limit of the pelvis is defined as the aortic bifurcation.
• WHO performance state 0-1
• Age >18 years
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion criteria

• Bone or visceral metastases
• Para-aortic lymph node metastases (above the aortic bifurcation)
• Local relapse in the prostate gland or prostate bed not suitable for a curative treatment
• Previous irradiation of the pelvic and or para-aortic nodes
• Serum testosterone level <50ng/dl or 1.7 nmol/L at time of randomization
• Symptomatic metastases
• Lymph node metastases in previously irradiated areas resulting in dose constraint violation
• Contraindications to pelvic radiotherapy (chronic pelvic inflammatory bowel disease)
• Contraindications to androgen deprivation therapy
• PSA rise while on active treatment with (LHRH-agonist, LHRH-antagonist, anti-androgen, estrogen
• Previous treatment with cytotoxic agent for PCa
• Treatment during the past month with products known to influence PSA levels (e.g. fluconazole, finasteride, corticosteroids,...)
• Other active malignancy, except non-melanoma skin cancer or other malignancies with a documented disease-free survival for a minimum of 3 years before randomization.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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196 participants in 2 patient groups

MDT + ADT

Other group

Description:

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + 6 months androgen deprivation therapy

Treatment:

Drug: androgen deprivation therapy

Radiation: metastasis-directed treatment

Procedure: salvage Lymph Node Dissection

MDT + WPRT + ADT

Experimental group

Description:

Metastasis-directed therapy (salvage lymph node dissection OR stereotactic body radiotherapy) + whole pelvic radiotherapy + 6 months androgen deprivation therapy

Treatment:

Drug: androgen deprivation therapy

Radiation: metastasis-directed treatment

Radiation: whole pelvic radiotherapy

Procedure: salvage Lymph Node Dissection