(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Valentina Guadalupi presented the results of the APPROACH trial, a pragmatic, randomized phase 3 trial that evaluates the addition of local treatment to ADT plus apalutamide in patients with metastatic hormone sensitive prostate cancer (mHSPC).
In addition to systemic treatment intensification, definitive local therapy in the form of pelvic radiotherapy has emerged as a standard of care approach for the management of low-volume mHSPC patients based on the results of two trials in this space: STAMPEDE (Arm H) and HORRAD.
STAMPEDE (Arm H) was an open label, randomized controlled phase III trial of 2,061 men with de novo mHSPC randomized to standard of care + radiotherapy or standard of care alone. Subgroup analysis by metastatic volume (CHAARTED criteria) was planned a priori. Radiotherapy, when stratified by metastatic burden, showed an overall survival (OS) benefit in the low volume group (HR: 0.68, 95% CI: 0.52 to 0.90) with restricted mean survival time improvement by 3.6 months from 45.4 to 49.1.1 HORRAD was a multicenter trial of 432 patients with previously untreated, de novo mHSPC randomized in a 1:1 fashion to either ADT with external beam radiotherapy or ADT alone. No subgroup analyses by CHAARTED volume criteria were performed, but subgroup analysis by number of metastatic lesions suggested potential (albeit not statistically significant) OS benefit for radiotherapy in patients with <5 metastatic sites (HR 0.68, 95% CI 0.42 to 1.10).2
To date, there are no randomized controlled trials published to assess the feasibility and clinical benefit of cytoreductive radical prostatectomy in the oligometastatic, hormone-sensitive setting. One of the stated rationales for performing a radical prostatectomy in this setting is to eliminate lethal clones of intra-prostatic, castrate-resistant disease, which can ameliorate treatment responses in the metastatic setting.
APPROACH (NCT05649943) is an Italian multicenter trial which will enrol 566 patients with oligometastatic hormone sensitive prostate cancer. All patients should be eligible for and receive apalutamide. Following 6 months of treatment, patients will be randomized in a 1:1 fashion to receive continued apalutamide plus local primary therapy (investigator's choice of primary radiotherapy versus cytoreductive prostatectomy) or continued apalutamide alone.
Eligibility criteria are as follows:
- Inclusion criteria:
- De novo low volume mHSPC
- No prior treatment with an anti-androgen or GnRH analogs prior to enrolment
- No prior history of systemic or local therapy for prostate cancer
- 99Tc bone scan positive with at least 1 bone lesion
- Exclusion criteria:
- Unfit for surgery or radiotherapy
- High cardiovascular risk
The primary outcome is radiographic progression-free survival. Secondary outcomes include:
- Tumor shrinkage after 6 months of apalutamide
- Short and long-term side effects following locoregional surgery or radiotherapy
- Time to PSA progression
- Time to castration resistance
- Cancer-specific survival
- OS
- Quality of life, assessed via the EPIC-26 and EQ-5D-5L questionnaires
Study accrual commenced March 2023 with an estimated completion date of January 2027.
Presented by: Valentina Guadalupi, MD, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.
References:- Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392(10162):2353-2366.
- Boeve LMS, Hulshof MCCM, Vis AN, et al. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. Eur Urol. 2019;75(3):410-418.