Timing of Radiotherapy (RT) After Radical Prostatectomy (RP): First Results from the RADICALS RT Randomised Controlled Trial (RCT) [NCT00541047]

Date 27 September 2019
Event ESMO 2019 Congress
Session Proffered Paper – Genitourinary tumours, prostate
Topics Prostate Cancer
Radiation Oncology
Genitourinary Cancers
Therapy
Presenter Chris Parker
Citation Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394
Authors C. Parker1, N.W. Clarke2, A. Cook3, H.G. Kynaston4, P. Meidahl Petersen5, W. Cross6, R. Persad7, C. Catton8, J. Logue9, H. Payne10, F. Saad11, K. Brasso12, H. Lindberg13, A. Zarkar14, R. Raman15, M.A. Roder5, C. Heath16, W.R. Parulekar17, M.K.B. Parmar18, M.R. Sydes19
  • 1Urology, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, SM2 5PT - Sutton/GB
  • 2The Departments Of Surgery And Urology, The Christie and Salford Royal Hospitals, Manchester/GB
  • 3Mrc Clinical Trials Unit At Ucl, Institute of Clinical Trials and Methodology-UCL, WC1V 6LJ - London/GB
  • 4Division Of Cancer And Genetics, Cardiff School of Medicine, CF144XN - Cardiff/GB
  • 5Oncology, University of Copenhagen, Rigshospitalet, DK-2100 - Copenhagen/DK
  • 6Department Of Urology, St James University Hospital, Leeds/GB
  • 7Bristol Urological Institute, North Bristol Hospitals, BS105NB - Bristol/GB
  • 8Radiation Oncology, Princess Margaret Hospital/ University Health Network, M5G2M9 - Toronto/CA
  • 9Oncology, The Christie Hospital, M20 4BX - Manchester/GB
  • 10Oncology, University College London Hospitals, NW12BU - London/GB
  • 11Urology, Hospital St. Luc du CHUM, H2X 3J4 - Montreal/CA
  • 12Clinical Medicine, University of Copenhagen, Rigshospitalet, 9, 2100 - Copenhagen/DK
  • 13Oncology, Herlev Hospital, 2670 - Herlev/DK
  • 14Oncology, University Hospital Birmingham, B152TH - Birmingham/GB
  • 15Clinical Oncology, Kent Oncology Centre, CT13NG - Canterbury/GB
  • 16Clinical Oncology, University Hospital Southampton, SO166YD - Southampton/GB
  • 17Oncology, Canadian Cancer Trials Group, K7L3N6 - Kingston/CA
  • 18Institute Of Clinical Trials & Methodology, MRC Clinical Trials Unit at UCL, WC1V 6LJ - London/GB
  • 19Mrc Clinical Trials Unit At Ucl, Institute of Clinical Trials and Methodology-UCL, WC1V6LJ - London/GB

Abstract

Background

The optimal timing of RT after RP for prostate cancer (PCa) is uncertain. RADICALS-RT compared the efficacy and safety of adjuvant RT (aRT) versus an observation policy with salvage RT for PSA failure (Obs+sRT).

Methods

Patients with post-op PSA≤0.2ng/ml and ≥1 risk factor (pT3/4, Gleason 7-10, positive margins or pre-op PSA≥10ng/ml) were randomised ≤22wk after surgery to aRT or Obs+sRT for PSA failure (PSA≥0.1ng/ml or 3 consecutive rises). Stratification factors were Gleason score, margin status, RT schedule (52.5Gy/20f, 66Gy/33f) and centre. The primary outcome measure (OM) was freedom-from-distant metastases (FFDM) with >1200 pts needed for 80% power to detect an improvement from 90% to 95% at 10yr with aRT. It is too early to present results on the primary OM, but we present secondary OMs: bPFS (any of PSA≥0.4ng/ml post-RT, PSA≥2.0ng/ml at any time, local/distant progression, deferred HT, PCa death), freedom-from-non-protocol hormone therapy (HT), safety (RTOG scale), and patient reported OMs (ICSmaleSF). Standard survival analysis methods were used.

Results

1396 pts were randomised (697 aRT, 699 Obs+sRT) from Oct-2007 to Dec-2016 (82% UK, 13% Denmark, 4% Canada, 1% Ireland). Median follow-up is 5yr. 93% (649/697) aRT started RT within 5mo; 33% (228/699) Obs+sRT started RT by 8yr after randomisation; 26% (166/649) aRT and 31% (71/228) Obs+sRT reported HT with their RT. With 169 events, bPFS at 5yr was 85% v 88% for aRT and Obs+sRT, respectively: HR = 1.10 (95%CI 0.81-1.49, p = 0.56). Freedom-from-non-protocol HT at 5yr was 92% v 94% (HR = 1.24, 95%CI 0.76-2.01, p = 0.39). Self-reported urinary incontinence was worse at 1yr in 5.3% vs 2.7% (p = 0.008), and RTOG Grade 3/4 urethral stricture was reported at any time in 8% vs 5% (p = 0.03), for aRT & Obs+sRT, respectively.

Conclusions

First results from RADICALS-RT do not show a benefit for aRT after RP in this patient group. Further follow-up is needed to report on long-term OMs, including FFDM. Adjuvant RT after RP increases risk of urinary morbidity. An observation policy with sRT for PSA failure should be the current standard after RP.

Clinical trial identification

ISRCTN 40814031.

Editorial acknowledgement

Legal entity responsible for the study

University College London.

Funding

Cancer Research UK, MRC Clinical Trials Unit at UCL, Canadian Cancer Trials Group.

Disclosure

C. Parker: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research Funding, Speaker Fees and Advisory Board Honoraria: Bayer; Advisory / Consultancy, Advisory Board Honoraria: AAA; Speaker Bureau / Expert testimony, Speaker Fees: Janssen. N.W. Clarke: Advisory / Consultancy, Consultation and advisory fees: Janssen. C. Catton: Advisory / Consultancy, Consulting fees: Bayer; Advisory / Consultancy, Research grant / Funding (self), Consulting fees and research support: AbbVie; Advisory / Consultancy, Consulting fees: Sanofi; Research grant / Funding (institution), Peer reviewed trial funding: Canadian Cancer Trials Group. H. Payne: Advisory / Consultancy, Speaker Bureau / Expert testimony, Paid lectures and advisory boards : Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Paid lectures and advisory boards: Astellas; Advisory / Consultancy, Paid advisory boards: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Paid lectures and advisory boards: Ferring; Advisory / Consultancy, Paid advisory boards: Ipsen. F. Saad: Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Astellas; Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Amgen; Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen; Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Bayer; Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Sanofi; Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Pfizer; Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca. H. Lindberg: Research grant / Funding (self), Non-remunerated activity/ies: Astellas Pharma; Research grant / Funding (self), Non-remunerated activity/ies: Bayer; Research grant / Funding (self), Non-remunerated activity/ies: Janssen; Research grant / Funding (self), Non-remunerated activity/ies: Sanofi Aventis; Research grant / Funding (self): Roche. A. Zarkar: Travel / Accommodation / Expenses, Support for attendance of a conference: Bayer; Speaker Bureau / Expert testimony, Educational meeting presentation: Pfizer; Speaker Bureau / Expert testimony, Chairing an educational meeting presentation: Janssen; Speaker Bureau / Expert testimony, Educational meeting presentation: Astellas; Research grant / Funding (self), IST: Sanofi. M.K.B. Parmar: Research grant / Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Astellas; Research grant / Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Clovis Oncology; Research grant / Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Novartis; Research grant / Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Pfizer; Research grant / Funding (institution), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Sanofi. M.R. Sydes: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research Funding, Speaker Fees and Advisory Board Honoraria: Bayer; Honoraria (self), Advisory / Consultancy, Advisory Board Honoraria: AAA; Speaker Bureau / Expert testimony, Speaker Fees: Janssen. All other authors have declared no conflicts of interest.