Radiation therapy compared to radical prostatectomy as first-line definitive therapy for patients with high-risk localised prostate cancer: An updated systematic review and meta-analysis

Figures & data

Figure 1. The selection process of the articles to assess survival outcomes among patients with high-risk prostate cancer who received RT compared to RP.

Table 1. Characteristics of the included studies of patients treated locally for high-risk prostate cancer

Study	Year	High-risk PCa definition	Sample size, n	Intervention group	Control group	Outcomes	Radiation dose
Yasui et al. Japan (1970–2014) [8]	2020	T3	4810	EBRT	RP+ sRT	OS/CSS	NR
Zhou et al. [9]	2020	T3	9258	EBRT EBRT+BT	RP	OS/CSS	NR
Muralidhar et al. NCDB and SEER (2004–2012) [10]	2019 NCBD/SEER	GS: 9–10	4367/2278	EBRT+BT	RP+aRT	OS	NR
Knipper et al. SEER 2004–2015 [11]	2019	GS: 9–10	16,018	EBRT	RP+aRT	OS/CSS	NR
Yin et al. SEER (2004–2015) [12]	2019	NCCN	62178	EBRT EBRT+BT	RP+aRT	OS/CSS	NR
Berg et al. NCDB (2004–2009) [13]	2019	NCCN	13985	EBRT+BT	RP	OS	NR
Jayadevappa et al. SEER–Medicare (1996–2003) [14]	2019	GS: ≥8 or T≥ T2c	4878	EBRT EBRT + BT	RP	OS/CSS	NR
Reichard et al. MD Anderson (2004–2013); comparison with matched SEER cohort [15]	2019	NCCN	304	EBRT	RP	OS/MFS	75.6 Gy
Ennis et al. NCDB (2004–2013) [16]	2018	NCCN	40123	EBRT EBRT+BT	RP	OS	NR
Tilki et al. Chicago Prostate Cancer Center, USA, and Martini-Klinik Prostate Cancer Center, Germany (1992–2013) [17]	2018	GS: 9–10	452	EBRT+BT	RP+aRT	CSS/OS	45 Gy IMRT + BT: ^125I (108 Gy), ^103Pa (90 Gy), ^131Cs (100 Gy)
Jang et al. SEER Medicare (1992–2009) [18]	2018	≥T3a or GS 8–10	7946	EBRT	RP+aRT	CSS/OS	NR
Kishan et al. University of California, Los Angeles (2000–2013) [19]	2018	NCCN	1373	EBRT EBRT+BT	RP	CSS/OS/ MFS	XRT: median 74.3 Gy XRT+BT: median 91.5 Gy
Robinson et al. NPCR of Sweden (1998–2012) [20]	2018	NCCN	41503	EBRT	RP	CSS
Markovina et al. Washington University, St. Louis (2002–2011) [21]	2018	NCCN	124	EBRT	RP	OS/MFS	Median 75.6 Gy
Gu et al. SEER (2004–2008) [22]	2018	NCCN	7656	EBRT	RP	CSS/OS	NR
Feldman et al. SEER–Medicare (1992–2009) [23]	2017	T3	2935	EBRT	RP	OS/CSS	NR
Ciezki et al. Cleveland Clinic (1996–2012) [24]	2016	NCCN	2042	EBRT	RP	CSS/BRFS	78 Gy
Taguchi et al. University of Tokyo (2005–2012) [34]	2015	D’Amico	336	EBRT	RP	OS/CSS/BRFS	Median 76 Gy
Yamamoto et al. Japan (1994–2005) [25]	2014	T3	231	EBRT	RP	OS/CSS	70 Gy (60–72)
Sooriakumaran et al. PCBaSe Sweden (1996–2010) [33]	2014	Modified NCCN	7649	EBRT	RP	CSS	NR
Merino et al. Pontificia Universidad Catolica de Chile (1999–2010) [26]	2013	D’Amico	294	EBRT	RP	CSS/BRFS	76 Gy
Hoffman et al. PCOS (1994–2010) [27]	2013	PSA >10 ng/mL or GS 8–10	437	EBRT	RP	OS/CSS	NR
Sun et al. SEER (1992–2005) [28]	2013	T2c	5945	EBRT	RP	OS/CSS	NR
Westover et al. 21st century oncology, Chicago Prostate Center, Duke University (1988–2008) [29]	2012	D’Amico	657	EBRT+BT	RP	CSS	45 Gy RT+ 90–108 Gy BT
Kibel et al. Barnes-Jewish Hospital and Cleveland Clinic (1995–2005) [30]	2012	D’Amico	1201	EBRT	RP	OS/CSS	Median 74 Gy (Barnes Jewish) and 78 Gy (Cleveland Clinic)
Abdollah et al. SEER (1992–2005) [31]	2012	T2c or GS 8–10	6057	EBRT	RP	OS/CSS	NR
Boorjian et al. MayoClinic, Fox Chase (1988–2004) [32]	2011	NCCN	1582	EBRT	RP	OS/CSS	72 Gy (50–79)

aRT: adjuvant RT; BRFS: biochemical recurrence-free survival; GS: Gleason score; IMRT: intensity modulated RT; NCDB: National Cancer Database; NCCN: National Comprehensive Cancer Network; NR: not reported; PCBaSe: Prostate Cancer data Base Sweden; PCOS: Prostate Cancer Outcomes Study; SEER: Surveillance, Epidemiology and End Results; sRT: salvage radiotherapy.

Table 2. The Newcastle-Ottawa scale for all studies in the quantitative synthesis

Study	Selection	Comparability	Outcome	Total
Yasui et al. [8]	****	**	**	8
Zhou et al. [9]	****	**	**	8
Muralidhar et al. [10]	****	**	**	8
Knipper et al. [11]	****	**	***	9
Yin et al. [12]	****	**	**	8
Berg et al. [13]	****	**	**	8
Jayadevappa et al. [14]	****	**	**	8
Reichard et al. [15]	****	**	**	8
Ennis et al. [16]	****	**	*	7
Tilki et al. [17]	***	**	*	6
Jang et al. [18]	****	**	**	8
Kishan et al. [19]	****	**	*	7
Robinson et al. [20]	****	**	*	7
Markovina et al. [21]	****	**	*	7
Gu et al. [22]	****	**	**	8
Feldman et al. [23]	****	**	**	8
Ciezki et al. [24]	****	**	**	8
Taguchi et al. [34]	****	**	*	7
Yamamoto et al. [25]	****	**	**	8
Sooriakumaran et al. [33]	****	**	***	9
Merino et al. [26]	****	**	*	7
Hoffman et al. [27]	****	**	***	9
Sun et al. [28]	****	**	*	7
Westover et al. [29]	***	**	*	6
Kibel et al. [30]	****	**	**	8
Abdollah et al. [31]	****	**	**	8
Boorjian et al. [32]	***	**	**	7

*According to Newcastle-Ottawa scale, stars were awarded for each quality item such that highest quality studies were awarded up to 9 stars.

Figure 2. (a) Forest plots with summary HRs (all included study) for OS of the RT group vs RP (reference group) for high-risk prostate cancer. (b) Forest plots with summary HRs (all included study) for CSS of the RT group vs RP (reference group) for high-risk prostate cancer.

Figure 3. (a) Forest plots with summary HRs (only EBRT) for OS of the RT group vs RP (reference group) for high-risk prostate cancer. (b) Forest plots with summary HRs (only EBRT) for CSS of the RT group vs RP (reference group) for high-risk prostate cancer.

Figure 4. (a) Forest plots with summary HRs (EBRT plus BT) for OS of the RT group vs RP (reference group) for high-risk prostate cancer. (b) Forest plots with summary HRs (EBRT plus BT) for CSS of the RT group vs RP (reference group) for high-risk prostate cancer.

Table 3. Reported data regarding multimodal therapy among studies that used EBRT plus BT compared to RP

Study	Adjuvant ADT, %		Adjuvant or salvage RT, %
	EBRT plus BT	RP	RP
Zhou et al. [9]	NR	NR	NR
Muralidhar et al. [10]	NR	NR	NR
Yin et al. [12]	NR	NR	NR
Berg et al. [13]	69	15	15
Jayadevappa et al. [14]	NR	NR	NR
Ennis et al. [16]	11.1	NR	NR
Tilki et al. [17]	1.0	8.8	15.7
Kishan et al. [19]	92.4	11.3	8.7
Westover et al. [29]	1.0	6	6

NR: not reported.

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