Exploration of Medicine

Table 1. Selected key radiotherapy trials addressing contemporary controversies

Controversy	Trial	Eligibility (PSA in ng/mL)	Arms	Outcomes
RT dose	MRC RT01 [63]	T1b-3a, N0, M0 PSA < 50	64 Gy/32 f vs. 74 Gy/37 f Conformal RT + neoadjuvant ADT	Improved bPFS, PFS Increased late bladder and bowel toxicities
Dose fractionation	CHiPP [64]	T1b-3a, N0, M0 PSA < 100	60 Gy/20 f vs. 74 Gy/37 f Conformal RT + neoadjuvant ADT	Non-inferior results
RT dose & ADT	Quebec randomized study, PCS III [54]	Favorable intermediate risk: only 1 risk factor, not GS 4 + 3/biopsy core ≥ 50%. The rest are unfavorable cases PSA > 10	ADT + 70 Gy + 6 m ADT ADT + 76 Gy + 6 m ADT 76 Gy alone	Favorable group: n.s. between the arms Unfavorable group: less biochemical failure with addition of ADT. Low cancer mortalities for all arms
RT pelvic coverage	RTOG 9413 [56]	T1c-4 and estimated 15% nodal risk PSA > 100	WP RT + NCHT PO RT + NCHT WP RT + AHT PO RT + AHT Neoadjuvant ADT or AHT. RT to pelvis: 50.4 Gy/28 f, prostate only: 70.2 Gy/39 f	4-year PFS: 60%* 44% 49% 50% P = 0.008

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ADT: androgen deprivation therapy; AE: adverse effect; AHT: adjuvant hormonal therapy; bPFS: biochemical progression-free survival; f: fraction; MRC: Medical Research Council; NCHT: neoadjuvant and concurrent hormonal therapy; n.s.: non-significant; PFS: progression-free survival; PO: prostate only; PSA: prostate-specific antigen; RT: radiation therapy; RTOG: Radiation Therapy Oncology Group; WP: whole pelvis; Gy: Gray is a unit of absorbed dose; m: months. * This arm has more grade 3 gastrointestinal complications

Declarations

Author contributions

PT, KW, EY, and DL: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. ES, KJ, GO, AJT, PM, AD, and RK: Writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

Kelvin Wong is a full-time employee of Astellas Pharma Canada, Inc. He was invited to assist with the literature review and drafting of this paper based on his scientific knowledge and experience in the therapeutic area. He does not have any conflicts to disclose aside from his employment with Astellas. No funding was received from Astellas for the drafting or publication of this paper. The assistance of Kelvin Wong in the drafting of this paper is solely in his individual capacity and is not a reflection of Astellas’ endorsement or approval of the paper’s content. Patricia Tai who is the Editorial Board Member and Guest Editor of Exploration of Medicine had no involvement in the decision-making or the review process of this manuscript. The remaining authors declare that they have no conflicts of interest.

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