Timing of radiotherapy (RT) after radical prostatectomy (RP): first results from the RADICALS RT randomised controlled trial (RCT) [NCT00541047]

C. Parker ¹,
N.W. Clarke ²,
A. Cook ³,
H.G. Kynaston ⁴,
P. Meidahl Petersen ⁵,
W. Cross ⁶,
R. Persad ⁷,
C. Catton ⁸,
J. Logue ⁹,
H. Payne ¹⁰,
F. Saad ¹¹,
K. Brasso ¹²,
H. Lindberg ¹³,
A. Zarkar ¹⁴,
R. Raman ¹⁵,
M.A. Roder ⁵,
C. Heath ¹⁶,
W.R. Parulekar ¹⁷,
M.K.B. Parmar ¹⁸,
M.R. Sydes ³

¹ Urology, The Institute of Cancer Research/Royal Marsden NHS Foundation Trust, Sutton, UK ² The departments of surgery and urology, The Christie and Salford Royal Hospitals, Manchester, UK ³ Mrc Clinical Trials Unit At Ucl, Institute of Clinical Trials and Methodology-UCL, London, UK ⁴ Division of cancer and genetics, Cardiff School of Medicine, Cardiff, UK ⁵ Oncology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark ⁶ Department of urology, St James University Hospital, Leeds, UK ⁷ Bristol Urological Institute, North Bristol Hospitals, Bristol, UK ⁸ Radiation oncology, Princess Margaret Hospital/ University Health Network, Toronto, Canada ⁹ Oncology, The Christie Hospital, Manchester, UK ¹⁰ Oncology, University College London Hospitals, London, UK ¹¹ Urology, Hospital St. Luc du CHUM, Montreal, Canada ¹² Clinical medicine, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark ¹³ Oncology, Herlev Hospital, Herlev, Denmark ¹⁴ Oncology, University Hospital Birmingham, Birmingham, UK ¹⁵ Clinical oncology, Kent Oncology Centre, Canterbury, UK ¹⁶ Clinical oncology, University Hospital Southampton, Southampton, UK ¹⁷ Oncology, Canadian Cancer Trials Group, Kingston, Canada ¹⁸ Institute of clinical trials & methodology, MRC Clinical Trials Unit at UCL, London, UK

Comments
Abstract

Publication: September 2019

https://oncologypro.esmo.org/Meeting-Resources/ESMO-2019-Congress/Timing-of-Radiotherapy-RT-After-Radical-Prostatectomy-RP-First-Results-from-the-RADICALS-RT-Randomised-Controlled-Trial-RCT-NCT00541047

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.

Prof. Tsaur

This so far largest trial should aid in solving the conundrum of the usage of radiotherapy in an adjuvant or salvage setting after radical prostatectomy. While adjuvant radiotherapy in the SWOG 8794 study yielded a 28% mortality risk reduction in pathologic stage T3 disease, the EORTC 22911 trial demonstrated no survival benefit. After recruitment of 1396 patients and follow-up of 5 years this early analysis demonstrated no advantage of adjuvant treatment regarding secondary outcomes biochemical progression-free survival and freedom from non-protocol hormonal therapy, but a higher toxicity as compared to salvage strategy. These findings support the use of early salvage radiotherapy for biochemical progression after radical prostatectomy.