The primary goal of this study is to determine if adding PET-directed local therapy improves
disease control compared to standard systemic therapy alone in Veterans with oligorecurrent
prostate cancer on PET/CT. The investigators will conduct a multi-institutional phase II/III
randomized trial comparing SST with or without PET-directed local therapy using radiation or
surgery to all metastases and if a local recurrence is present.
Prostate Cancer is the most commonly diagnosed cancer among Veterans, comprising 30% of new
cancer diagnoses in the VA. Eighty-five percent of men present with localized prostate
cancer, which is typically treated with active surveillance or curative local therapy using
surgery or radiation therapy. Unfortunately, twenty percent of Veterans undergoing curative
local therapy will develop metastatic recurrence. These men typically receive palliative
systemic hormonal therapy to control the participants disease. Despite this, over half of men
will have cancer progression within 1-2 years and half will die within 5 years.
Two diverging paradigms have been studied in recent years to improve the survival of men with
recurrent metastatic prostate cancer. First, a subset of patients has oligorecurrent disease,
defined as 1-5 sites of metastases. These patients are hypothesized to have an intermediate
clinical state in which ablative local therapy with surgery or radiation to all metastatic
sites of disease (metastasis-directed therapy; MDT) can lead to durable disease control and
potentially cure in select patients. Recent Phase II randomized trials have demonstrated
improved long-term progression-free survival with MDT in the absence of systemic therapy.
Yet, 75% of patients receiving MDT for oligorecurrent cancer develop progression in new
areas, arguing that systemic therapy is needed to treat occult metastases. This is supported
by data demonstrating that earlier palliative hormonal therapy is associated with improved
survival. In fact, the second approach that has been studied in recent years, is whether
escalating hormonal therapy by adding novel androgen receptor axis targeted agents or
chemotherapy improves outcomes in men with metastatic prostate cancer. Multiple phase III
randomized trials demonstrate that escalating hormonal therapy with these novel therapeutic
agents improves progression-free survival and overall survival dramatically. Therefore, these
agents have been integrated as an option into today's standard systemic therapy (SST) for
metastatic recurrence.
Given the promise of MDT to induce long-term cancer control and the effectiveness of SST to
prevent further cancer progression, there is an urgent need to determine whether adding MDT
to SST improves disease outcomes further. Additionally, prior studies have excluded patients
with local recurrence. However, these comprise a large proportion of Veterans with
oligorecurrent prostate cancer.
The primary goal of the investigators study is to determine if adding PET-directed local
therapy (treatment of local recurrence on PET/CT and/or MDT) improves disease control
compared to SST alone in Veterans with oligorecurrent prostate cancer. The investigators will
conduct a multi-institutional phase II/III randomized trial comparing SST with or without
PET-directed local therapy. Other goals of the study are to determine any differences in
patterns of cancer progression, survival, and quality of life. The investigators also will
determine if certain mutations present in tumor DNA can predict if Veterans will benefit from
PET-directed local therapy and encourage banking of tumor tissues for future analyses in a
separate tumor registry study (VA MAPP).
Inclusion Criteria:
- Age 18 years and ECOG performance status 2.
- Histologically or cytologically confirmed prostate adenocarcinoma.
- Prior curative-intent local therapy with either upfront definitive radiotherapy (any
modality) or prostatectomy +/- post-operative radiotherapy for localized prostate
cancer
- Any T-classification, Gleason's Grade Group, and pre-treatment PSA at the time of
initial curative-intent
- treatment are acceptable.
- Nx, N0, or N1 N-classification at the time of curative-intent local therapy
- No metastatic disease at the time of curative-intent local therapy
- Rising PSA suspicious for biochemical recurrence after local therapy. In general, this
will be defined as:
- PSA 0.2 ng/ml x 2 after prostatectomy +/- post-operative radiotherapy
- Elevation of PSA 2 ng/ml above the nadir after definitive radiotherapy
- Two consecutively rising PSAs with evidence of metastasis on the imaging studies
described in 5.6
- The following lab studies must be performed within 90 days of enrollment (except in
patients who have already started SST):
- PSA
- Total testosterone > 100 ng/dl
- The following imaging studies must be performed within 90 days of enrollment (except
in patients who have started SST):
- CT or MRI abdomen/pelvis
- Technetium (Tc99m-MDP) or sodium fluoride (NaF) bone scan (sodium fluoride
preferred)
- FDA-approved standard of care PET/CT (currently PSMA, Fluciclovine, choline,)
- The imaging studies in 6 reveal a total of 1-5 lesions suspicious for nodal recurrence
or metastasis from prostate cancer as determined by the official report.
- Veterans with radiographic evidence of local recurrence: There must be recurrence on
imaging in at least one other site in addition to a local recurrence in the prostate,
seminal vesicles, or prostate bed. In other words, patients with a local recurrence in
the prostate, prostate bed, or seminal vesicles only are not eligible. The Veteran
must be a candidate for salvage local therapy.
- If a Veteran has started SST for this recurrence prior to enrollment, he is eligible
if all of the following criteria are met:
- He has been on SST for 120 days.
- The imaging studies required for enrollment were performed within 90 days prior
to the SST start date. These studies will be entered as the enrollment studies.
- Biochemically recurrent PSA and serum testosterone > 100 ng/dl within 90 days
prior to SST start.
- There is no evidence of castration-resistant prostate cancer (see section 11.4
for definition of castration-resistant prostate cancer)
- No other prior malignancy is allowed except for the following: adequately treated
non-melanomatous skin cancer, adequately treated Stage 0, I, or II cancer from which
the patient is currently in complete remission, or any other cancer from which the
patient has been disease free for three years.
Exclusion Criteria:
- Any current or prior evidence of castration-resistant prostate cancer (two consecutive
rises in serum PSA, obtained at a minimum of 1-week interval, with the final PSA value
1 ng/ml, while having a total testosterone < 50 ng/dl).
- Presence of a symptomatic metastasis that requires palliative radiotherapy.
- Any known brain metastases, presence of leptomeningeal disease, malignant spinal cord
compression, or malignant cauda equina syndrome are not eligible.
- Prior nodal, bone, or visceral metastasis after curative-intent therapy other than
those identified on the enrollment imaging studies, whether treated or untreated.
- Prior local therapy with surgery or radiation to the nodal or distant metastases
identified on the enrollment PET/CT.
- Prior radiation therapy to any sites requiring PET-directed local therapy or salvage
local therapy that will lead to prohibitively high risk of toxicity from subsequent
local therapy, as determined by the treating radiation oncologist or
surgeon/urologist.
- Any other previous or current condition, which, in the judgement of the responsible
clinician, is likely to interfere with any STARPORT treatments or assessments.
- Patients with psychiatric illness/social situations that would limit compliance with
study requirements.
