Combination cytoreductive surgery, radiotherapy, or ablation for De Novo metastatic prostate cancer: The IP2-ATLANTA Internal Pilot, Phase 2, randomised controlled trial.

Connor, Martin J., Shah, Taimur T., Sukumar, Johanna, Basak, Dolan, Fiorentino, Francesca, Heath, Catherine, Horan, Gail, Johnson, Nicholas, Khoo, Vincent, Khoubehi, Bijjan, Klimowska-Nassar, Natalia, Mangar, Stephen, McGrath, John, Nohpal de la Rosa, Consuelo, Price, Derek, Rai, Bhavan, Sarwar, Naveed, Smith, Andrew, Staffurth, John N. ORCID: https://orcid.org/0000-0002-7834-3172, Tam, Henry, Thippu Jayaprakash, Kamal, Winkler, Mathias, Dudderidge, T., Ahmed, Hashim U. and IP2-ATLANTA Trial Investigators 2025. Combination cytoreductive surgery, radiotherapy, or ablation for De Novo metastatic prostate cancer: The IP2-ATLANTA Internal Pilot, Phase 2, randomised controlled trial. European Urology Oncology 10.1016/j.euo.2025.05.010

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Abstract

Cytoreduction of the primary prostate cancer, involved lymph nodes, and metastases may confer improved cancer control in de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC). Herein, we aimed to examine the safety and feasibility of novel cytoreductive therapies. We report the internal pilot of IP2-ATLANTA, a phase 2, multicentre, three-arm, randomised controlled trial. Patients with histologically diagnosed mHSPC of performance status 0-2 were randomly allocated (1:1:1) to the standard of care control group or one of two intervention arms, and stratified by CHAARTED-defined metastatic burden, intent to treat pelvic lymph nodes, and use of docetaxel and stereotactic ablative body radiotherapy (SABR; three or fewer metastases). The minimally invasive ablative therapy (MIAT) arm included cytoreductive prostate ablation with pelvic lymph node dissection (PLND), if involved, followed by SABR for metastases. The radical arm included treatment of the prostate with external beam radiotherapy along with pelvic lymph node radiotherapy (PLNRT), if involved, or cytoreductive radical prostatectomy with PLND, if involved, both followed by SABR for metastases. Systemic therapy was lifelong androgen deprivation therapy with docetaxel or an androgen receptor targeted agent. Repeat pretreatment prostate magnetic resonance imaging and biopsy were carried out. Pilot coprimary endpoints were complete pathological response, randomisation feasibility, and safety. Between April 26, 2019 and February 6, 2021, 108 patients met the eligibility criteria, of whom 81 underwent randomisation (75% [81/108, 95% confidence interval {CI} 65.7-82.8]), exceeding the target recruitment rate. The median follow-up period was 25 mo (interquartile range [IQR] 20-30), age 69.0 yr (IQR 62-74), and prostate-specific antigen 80.50 ng/ml (IQR 20.25-261.78). Metastatic burden was balanced (low 51%; high 49%). Performance status was 0 in 74/81 (91%) patients, with 69/81 (85%) receiving doublet systemic therapy. Cytoreductive interventions performed were as follows: MIAT ± PLND in 23/27 (85%), prostatectomy ± PLND in 5/26 (19%), and radiotherapy ± PLNRT in 14/26 (54%). Among patients with prostate tissue for histopathological assessment, a complete pathological response occurred in 11% (6/53 [95% CI 4.3-23.0]; 11% [3/27] MIAT; 12% [3/26] radical). Grade 3 or worse adverse events were reported in 18% (5/28) of the control group, 7% (2/26) of the MIAT group, and 15% (4/26) of the patients receiving radiotherapy or prostatectomy. Randomisation to combination cytoreductive surgery, radiotherapy, and ablation was feasible. Cytoreductive treatment combinations were well tolerated and deserve further evaluation. The majority of patients still have viable residual prostate cancer after systemic therapy.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Elsevier
Date of First Compliant Deposit:	4 July 2025
Date of Acceptance:	14 May 2025
Last Modified:	04 Jul 2025 09:00
URI:	https://orca.cardiff.ac.uk/id/eprint/179540

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