PEARLS – a multicentre phase II/III trial of extended field radiotherapy for androgen sensitive prostate  cancer patients with PSMA‐avid pelvic lymph nodes at presentation


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Julia Murray1, Clare Cruickshank2, Philip Bell3, Thomas Bird4, John Braun3, Dave Chuter3, Miguel Ferreira5, Clare Griffin2, Nabil Hujairi1, Alan Melcher2, Elizabeth Miles6, Olivia Naismith1, Miguel Panades7, Lara Philips2, Alison Reid1, Jan Rekowski2, Peter Sankey8, John Staffurth9, Isabel Syndikus10, Alison Tree1, Anna Wilkins2, Reena Davda11, Emma Hall2
1Royal Marsden NHS Foundation Trust, 2Institute of Cancer Research (ICR), 3Other, 4University Hospitals Bristol NHS Foundation Trust, 5King’s College London (KCL), 6Mount Vernon Cancer Centre, 7Lincoln County Hospital, 8Plymouth Hospitals NHS Trust, 9Velindre NHS Trust, 10Clatterbridge Cancer Centre NHS Foundation Trust, 11University College London Hospitals NHS Foundation Trust (UCLH)

Abstract

Background

Prostate cancer is the most common male cancer in the UK with around 48,500 men diagnosed each year.  In 2017, 1,973 prostate cancer patients in the UK were diagnosed with N1 disease.

PEARLS (CRUK/19/016) aims to show that, compared to standard field radiotherapy, extended field radiotherapy covering the prostate, pelvis and para-aortic lymph nodes (LN) improves outcomes for prostate cancer patients with PSMA-avid pelvic LN at presentation.  The trial is registered: ISRCTN36344989.

Method

PEARLS is a multi-stage randomised controlled trial. Men with histologically confirmed prostate cancer with PSMA-avid nodal disease within the pelvis +/- para-aortic region receiving androgen deprivation therapy +/- androgen receptor targeted therapy or docetaxel chemotherapy are eligible. Patients will be randomised (1:1) to standard field intensity modulated radiotherapy (IMRT) (control) or extended field IMRT (experimental) with stratification by extent of LN disease determined by PSMA-PET/CT (pelvic only vs. para-aortic).

All participants will receive IMRT given in 20 fractions over 4 weeks. In the control group, participants will receive 60Gy to prostate (and 44Gy to pelvis with an integrated boost of 51Gy to involved LN for patients with pelvic-node disease only). In the experimental group, participants will receive 60Gy to the prostate and 44Gy to the pelvis and para-aortic region with an integrated boost of 51Gy to involved LN. In phase II, the primary endpoint is acute lower gastrointestinal RTOG grade 2+ toxicity. If unacceptable toxicity is seen in the first 75 participants receiving extended field radiotherapy then recruitment will stop; otherwise the study will continue. In phase III, the primary endpoint is metastasis-free survival. The trial aims to recruit 714 patients with pelvic-node disease to detect a hazard ratio of 0.62 in favour of extended field radiotherapy and 179 patients with para-aortic disease.

In selected centres, participants will be asked to donate blood, tissue and stool samples and undergo follow-up PSMA-PET/CT imaging for translational research.

The trial was launched in June 2021. Phase II will be conducted in 20 NHS Trusts across the UK.

Results


Conclusion


Impact statement

This trial will determine the optimal radiotherapy field for node positive prostate cancer patients and potentially extend the envelope of cure.