AUA 2023: Updates on Clinical Trials in Prostate Cancer

( Dr. Russel Szmulewitz provided a brief update on clinical trials in prostate cancer. He started by highlighting the clinical states of prostate cancer, beginning in the non-castrate clinically localized setting and extending to the late stage metastatic castration resistant prostate cancer.


clinical states of prostate cancer

As noted above these serve as a framework for clinical intervention and regulatory settings for clinical trials. However as treatment intensification continues and treatments are moved earlier into the treatment paradigm, some of the above nomenclature is becoming obsolete.

The goal of today is to provide a snapshot of key ongoing clinical trials most relevant to a urologic oncologist in the following disease states:

  • high risk localized disease
  • recurrent castration cM0 sensitive prostate cancer (CSPC)
  • first line metastatic castration sensitive prostate cancer (mCSPC)
  • emerging and exciting potential trials

First, we begin with treatment intensification and localized PCa-building on androgen deprivation therapy (ADT) alone.

building on adt

There has been a lot of published work in this area already. Urotoday has covered all of it! he highlights a few upcoming and ongoing trials.

  • PROTEUS (NCT03767244) - Evaluate apalutamide in men with high risk localized or locally advanced prostate cancer who are undergoing radical prostatectomy. Patients are treated with apalutamide and ADT preop and postop for six months. The trial has already accrued the target of 2000 patients. The primary endpoint is pathologic complete response and metastasis free survival.
  • GUNS (NCT04812366) - This is a genomic biomarker selected umbrella neoadjuvant study for high risk localized prostate cancer. this is a unique study in which patients undergo genomic profiling of their prostate biopsy tissue and are assigned, based on profiling, into one of four categories. This results in treatment with ADT plus apalutamide or abiraterone and a specific targeted agent (docetaxel, niraparib, atezolizumab) for 16 weeks. the primary endpoint is pathologic complete response. They are currently in ruling with the target accrual of 315 patients.

Next, he moved on to the clinical M0 castration sensitive prostate cancer space. these are the patients with biochemical recurrence looking at salvage therapy.

  • FORMULA-509 - Patients with recurrent prostate cancer after prostatectomy were randomized to either receive salvage radiation with six months ADT OR salvage radiation with six months ADT and abiraterone and apalutamide.
    • GU ASCO 2023 - primary endpoint was three-year progression free survival, HR 0.80. it was a negative primary endpoint.
  • NRG GU-008: Randomized phase three trial incorporating apalutamide and advanced imaging into salvage therapy for patients with node positive prostate cancer after radical prostatectomy. this is currently enrolling and their target accrual is 586. Primary endpoint is metastasis free survival.
  • AFT-19 PPRESTO - Patients with biochemical recurrence after radical prostatectomy or primary radiotherapy who have no evidence of metastases were randomized to treatment with either ADT alone ADT plus apalutamide or ADT plus apalutamide and abiraterone.
    • ESMO 2022 - Median PSA-PFS was better with apalutamide (24.9 months vs. 20.3 months, HR 0.52)
    • Final results have not yet been presented
  • ARASTEP - patients with biochemical recurrence after primary therapy and psma pet positive disease. Randomized to darolutamide/ADT vs. ADT alone, but SBRT/surgery for mets allowed. This study is expecting an accrual of 750 patients and is actively enrolling. Primary endpoint will be metastasis free survival by PSMA PET/CT.

Next, we moved on to the mCSPC setting. the main questions being asked are:

  • do we need docetaxel and triplet therapy?
  • can we de-escalate (iADT) in the modern era?
  • is there any improvement on standard of care?
  • what is the role for precision or molecularly driven therapeutics?

He highlighted the following studies:

  • PSMAddition - International prospective open label randomized phase III study comparing Lutetium-PSMA in combination with SOC vs. SOC alone. They are expecting and accrual of 1126 patients, and they are actively accruing now. Primary endpoint will be radiographic progression free survival.
  • CAPItello-281 - Phase three double-blind randomized placebo-controlled trial assessing Capivasertib + Abiraterone vs. Abiraterone+placebo in patients de novo PTN loss on central IHC. With an expected accrual of 1000 patients, they are actively enrolling. Primary endpoint is again radiographic progression free survival.

Lastly, he highlighted some new and promising trials.


  • ARV-110 – an Androgen Receptor PROTAC degrader. It is an oral agent that promotes the degradation of the androgen receptor.
  • ODM-208 - Steroid biosynthesis inhibitor.


  • PSMA-targeted (Actinium-PSMA-617, Lu177-PSMA-I&T)
  • KLK2 targeted

Novel immunotherapies

  • Cabozantinib-atezolizumab phase III trial (NCT044461117)
  • T-cell engagers (PSMA, STEAP1)
  • B7-H3 antibodies
  • CAR-T?

In conclusion, he notes that prostate cancer standards are rapidly evolving and this is an active time for clinical research. Moving known active therapies forward is the next wave. Precision therapy and perhaps novel immune strategies will hopefully get us closer to a cure.

Presented by: Russel Z. Szmulewitz, MD, Associate Professor of Medicine, University of Chicago, Chicago, IL

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Associate Professor of Urology, University of California, Davis @tchandra_uromd @UCDavisUrology on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023