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Table 1 Overview of publications included in the systematic review reporting metastasis-directed radiotherapy for oligometastatic prostate cancer

From: Radiotherapy of oligometastatic prostate cancer: a systematic review

Source

Year

Study design

Maximal numbers of metastases

n (patients/lesions)

Median FU (month)

Imaging method

Site of metastases

Median dose (range) and fractions

Concomitant ADT (%)

Median ADT-FS (month)

Local control

PFS

Jereczek-Fossa [82]

2012

Retrospective analysis

1

19/19

16.9

CT, Bone Scan, Choline-PET/CT

LN 95%, Bone 5%

LN 33 Gy/3 fr, Bone 36 Gy/3 fr

74%

NR

100% (at last FU, median 16.9 mo)

42.6% (30-month PFS)

Tabata [30]

2012

Retrospective analysis

5

35/NR

36

NR

Bone 100%

40 Gy (30–50 Gy)/10–25 fr

100%

NR

NR

Ahmed [61]

2013

Retrospective analysis

5

17/21

6

CT, MRI, Choline-PET/CT

LN 5%, bone 90%, viscera 5%

LN 50 Gy/5 fr, Bone: 20 Gy (18–30 Gy)/1–3 fr, Liver 60 Gy/3 fr

88%

NR

100% (6 mo)

74/40% (1-/2-year FFDP)

Berkovic [14]

2013

Retrospective analysis

3

24/29

24

MRI, Bone Scan, FDG-PET/CT, Choline-PET/CT

LN 45%, bone 55%

50 Gy (40–50 Gy)/10 fr (8–10)

0%

38

100% (2 year)

72/42% (1-/2-year CPFS)

Muacevic [31]

2013

Retrospective analysis

2

40/64

10

Choline-PET/CT

Bone 100%

20 Gy (16.5–22 Gy)/1 fr

48%

NR

95.5% (2 year)

NR

Schick [6]

2013

Retrospective analysis

4

50/79

31

MRI, Bone Scan, Choline-PET/CT

LN 63.5%, bone 31.5%, viscera 5%

pelvic LN: 50.4 Gy + Boost to median 65 Gy (44–74 Gy) Bone 28–36 Gy/5–6 fr

98%

NR

NR

58.6/54.5% (3-year CFFS/BPFS)

Decaestecker [15]

2014

Prospective analysis

3

50/70

24

MRI, Choline-PET/CT, FDG-PET/CT

LN 54%, bone 44%, viscera 2%

50 Gy/10 fr, or 30 Gy/3 fr

70%

25

100% (2 year)

64/35% (1-/2-year)

Detti [83]

2015

Retrospective analysis

2

30/39

12

CT, MRI, Choline-PET/CT

LN 100%

Most commonly used 30 Gy (24–36 Gy)/3 fr (1–5)

47%

NR

100% (1 year)

NR

Ponti [57]

2015

Retrospective analysis

2

16/18

29

Choline-PET/CT

LN 100%

35 Gy (12–35 Gy)/5 fr (1–5)

63%

Mean 23.7

94% (6 mo)

45% (2-year BPFS)

Muldermans [7]

2016

Retrospective analysis

5

66/81

16

CT, MRI, Bone Scan, Choline-PET/CT

LN 7.4%, bone 91%, viscera 1%

16 Gy (16–50 Gy)/1 fr (1–5)

64%

NR

82% (2 year)

45/54% (2-year DPFS/BPFS)

Napieralska [75]

2016

Retrospective analysis

4

18/31

16

CT, MRI, Choline-PET/CT

LN 100%

30 Gy (24–45 Gy), 2–5 fr

100%

93/70% (1/2 year)

NR

Ost [16]

2016

Retrospective analysis

3

119/163

36

MRI, Choline-PET/CT, FDG-PET/CT

LN 60%, bone 36%, mixed 2%, viscera 1%

 ≥ 80 Gy BED (α/β 3), SD ≥ 5 Gy

50%

Median time from first SBRT to palliative ADT: 28 m

93/92% (3/5 year)

31/15% (3-/5-year DPFS)

Pasqualetti [17]

2016

Prospective clinical trial

3

29/45

12

Choline-PET/CT

LN 56%, bone 44%

24 Gy/1 fr or 27 Gy/3 fr

0%

39.7

100% (at last FU, median 12 mo)

NR

Wu [8]

2016

Retrospective analysis

3

30/53

33

Bone Scan, Choline-PET/CT

Bone 100%

Short-Course: 20-30 Gy/5–10 fr, Long-course 37.5–50 Gy/15–25 fr

100%

75% (3 year)

22.8% (3-year)

Bouman-Wammes [46]

2017

Retrospective double arm

4

43/55

31

Choline-PET/CT

LN (77%), bone (21%), mixed (2)

Most commonly used 30 Gy/3 fr and 35 Gy/5 fr

0%

15.6 m

100% (at last FU, median 2.6 year)

NR

Fodor [26]

2017

Retrospective analysis

2

81/NR

36

Choline-PET/CT

LN (100%)

51.8 Gy/28 fr + SIB 65.5 Gy (TD 50–65 Gy/25–30 fr)

72%

NR

89.8% (3 year)

61.8/42.4%(3-year CRFS/BPFS)

Habl [32]

2017

Retrospective analysis

2

15/20

23

MRI, PSMA-PET/CT, Choline-PET/CT

Bone 100%

25–40 Gy

20%

9.3

100% (2 year)

NR

Ingrosso [71]

2017

Retrospective analysis

2

40/47

24

Choline-PET/CT

LN 100%

Most commonly used: 35 Gy/5 fr and 40 Gy/8 fr (12–50 Gy/1–5 fr)

48%

Mean 26

98% (30 mo)

44% (2-year BPFS)

Jereczek-Fossa [9]

2017

Retrospective analysis

5

94/124

19

CT, MRI, Choline-PET/CT

LN 100%

Most commonly used: 24 Gy (15–36 Gy)/3 fr ( 3–6)

36%

7

84% (2 year)

30% (2-year)

Triggiani [18]

2017

Retrospective double arm

3

141/209

OR: 20.4/OP: 23.4

CT, Bone Scan, Choline-PET/CT

LN 84.1.%/70%, bone 15.8%/30%

116 Gy BED (80–216.6 Gy) (α/β 3 Gy)

24%

OR: 21/OP: 22 (second systemic therapy-free survival)

OR: 92.8%/OP: 90.2% (2 year)

OR: 64.4/43/26.6% (1-/2-/3-year) OP: 43.2/21.6/11.9%

Baumann [45]

2018

Retrospective analysis

5

5/18

11

PSMA-PET/CT

LN 21%, bone 79%

35 Gy/5 fr

0%

NR

88% (at last FU, median 11 mo, determined by PET-response)

NR

Fanetti [33]

2018

Retrospective analysis

5

55/77

25

MRT, PSMA-PET/CT, Choline-PET/CT

Bone 100%

24 Gy (15-30 Gy)/3 fr (1–5)

55%

NR

83/76% (1/2 year)

55/27% (1-/2-year CPFS), 51/13% (1-/2-year BPFS)

Franzese [19]

2018

Retrospective analysis

3

64/90

15.2

Bone Scan, Choline-PET/CT

LN 78%, bone 16%, mixed 3%, viscera 3%

42 Gy (18–60)/2–8 fr

42%

NR

88/84% (1/1.5 year)

52/37% (1-/1.5-year DPFS), 38/25% (1-/1.5-year CPFS)

Guler [50]

2018

Retrospective analysis

3

23/38

7

PSMA-PET/CT

LN 43%, bone 43%, both 23%

45 Gy (30–64 Gy)/15 fr (12–27)

100%

100% (1 year)

51% (1 year)

Lépinoy [59]

2018

Retrospective double arm

4

62/88

42

Choline-PET/CT

LN 100%

Extended field: 45–59 Gy in 1.8–2.2 Gy + Boost to median 66 Gy Involved field: 36 Gy (30–66) in 7.5 Gy (2–15)

24%

NR

NR

Extended field: 88.3%/involved field: 55.3% (3-year FFR)

Oertel [21]

2018

Retrospective analysis

LN 5/Bone 1

27/37

NR

CT, MRI, PSMSA-PET/CT, Choline-PET/CT

LN 79%, bone 30%

LN: 63 Gy (30.6–70.2 Gy), Bone: 54 Gy (30–66.6 Gy)

74%

NR

100% (2 year)

LN: 75.4/58.7% (1-/2-year MFS), Bone: 100/83.3%

Ost [60]

2018

Prospective randomized phased II study

3

Surveillance: 31/65, MDT 31/51

36

Choline-PET/CT

LN 55%, bone 39%, mixed 5%, viscera 2%

30 Gy/3 fr

0%

21 versus 13 (p = 0.11)

100 vs. 77% at last FU, median 36 mo

NR

Siva [62]

2018

Prospective clinical trial

3

33/50

24

CT, Bone Scan, NaF-PET/CT

LN 36%, bone 61%, mixed 3%

20 Gy/1 fr

33%

2 year ADT-FS: 48%

97/93% (1/2 year)

58/39% (1-/2-year DPFS)

Steuber [84]

2018

Retrospective matched pair analysis

5

263/NR

70

Choline-PET/CT

LN 100%

 ≥ 80 Gy BED (α/β 3), SD ≥ 5 Gy

NR

NR

NR

NR

Tran [76]

2018

Retrospective analysis

5

53/108

44

MRI, Bone scan, Choline-PET/CT,

LN 100%

45–50.4 Gy on involved LN regions, Boost median to 64.4 (54–69)

100%

96.3% (at last FU, median 44 mo)

58.2/43%(5-year DPFS/BPFS)

Henkenberens [51]

2018

Retrospective analysis

2

29/NR

8

PSMA-PET/CT

LN 58.6%, Bone (20.7%), mixed 3.4%

LN (50.4–54.0 Gy), Bone (40 Gy à 2.5 Gy 4x/week)

28%

NR

100% (at last FU, median 8 mo)

75% (1-year DMFS and BPFS)

Loi [85]

2018

Retrospective analysis

2

23/27

22

Choline-PET/CT

LN 100%

24 Gy/1 fr

0%

NR

NR

65/40/26% (6-mo/1-year /2-year BPFS)

Soldatov [54]

2018

Retrospective analysis

5

108/284

18

PSMA-PET/CT

LN 59%, bone 39.6%, viscera 1.4%

LN 50.4–60 Gy in 1.8 Gy, Bone 40 Gy in 2.5 Gy 4x/week

NR

NR

96,3% (at last FU, median 18 mo)

56,5% (BPFS at 18 mo)

Kneebone [20]

2018

Prospective clinical trial

3

57/73

16

PSMA-PET/CT

LN 65%, bone 31%, mixed 4%

LN 30 Gy/3 fr or 50 Gy/5 fr, Bone 20 Gy/1 fr or 24 Gy/2 fr

0%

NR

100% (at last FU, median 16 mo)

46/16% (1-/2-year BPFS)

Cysouw [10]

2018

Retrospective analysis

4

40/50

33

Choline-PET/CT

LN 74%, bone 26%

35 Gy/5 fr or 30 Gy/3 fr

NR

NR

NR

NR

Patel [34]

2019

Retrospective analysis

3

51/64

23

MRI, Bone Scan PSMA-PET/CT, Choline-PET/CT

Bone 100%

30 Gy (24–30 Gy)/3–6 Gy SD

79%

NR

98/95/90% (1/2/3 year)

45/38% (1-/2-year PFS)

Triggiani [24]

2019

Retrospective analysis

5

86/117

31

Bone Scan, Choline-PET/CT

LN 67%, bone 33%

LN 36 Gy/6 fr or 45 Gy/6 fr; Bone 24 Gy/3 fr

0%

Median systemic treatment-free survival 21.8

80% (at last FU, median 31 mo)

52/34% (1-/2-year DPFS)

De Bleser [48]

2019

Retrospective analysis

5

506/764

36

CT, MRI, PSMA-PET/CT, Choline-PET/CT, FDG-PET/CT

LN 100%

SBRT minimal SD 5 Gy, maximum of 10 fractions; ENRT: minimal TD 45 Gy/up to 25 fx

SBRT: 23%, ENRT: 60%

NR

NR

68/77% (SBRT vs. ENRT 3-year MFS, p = 0.01)

Bowden [22]

2019

Prospective clinical trial

5

199/NR

35

MRI, Bone Scan, PSMA-PET/CT, Choline-PET/CT

LN 63.3%, bone 22.6%, mixed 12.1%, viscera 2%

50 Gy/10 fr

7%

Median treatment escalation-free survival: 27.1

NR

NR

Gomez-Iturriaga [63]

2019

Prospective clinical trial

5

49/102

24

MRI, Choline-PET/CT

LN 69.4%, bone 26.5%, mixed 4.1%

Bone 24–30 Gy/3 fr, LK 45 Gy + SIB 58 Gy/25 fr or 24 -30 Gy/3 fr

Yes, proportion NR

NR

91.8% (at last FU, median 24 mo)

71% at last FU, 2-year BPFS: 74.2%

Artigas [42]

2019

Retrospective analysis

3

20/30

15

PSMA-PET/CT

LN 60%, bone 30%, viscera 10%

30 Gy/3 fr or Pelvic + SIB up to 66 Gy

0%

2 year ADT-FS: 74%

NR

79/53% (1-/2-year BPFS)

Franzese [49]

2019

Retrospective analysis

5

92/119

22

PSMA-PET/CT, Choline-PET/CT

LN 76%, bone 24%, viszera 3%

42 Gy (18–60 Gy)/2–8 fr

NR

NR

90.9/85.5% (1/3 year)

51.9/20.9% (1-/3-year DPFS), 42.8/16.7% (1-/3-year PFS)

Ong [23]

2019

Retrospective analysis

3

20/26

16

PSMA-PET/CT

LN 75%, bone 15%, mixed 10%

Bone 30 Gy/3 fr, LK 35–40 Gy/5 fr

0%

1-year ADT-FS: 70%

93% (1 year)

62% (1-year)

Nicosia [53]

2019

Retrospective analysis

5

109/155

16

PSMA-PET/CT, Choline-PET/CT

LN 100%

36 Gy (25–48 Gy)/4–7 fr

46%

15

93/87% (1/2 year)

55/33% (1-/2-year PFS), 64/52% (1-/2-year nodal PFS)

Berghen [47]

2019

Retrospective analysis

3

30/45

18

CT, MRI, PSMA-PET/CT, Choline-PET/CT

LN 17%, Bone 66%, both 3%, viscera 3%,

SBRT: EQD2 78–142.8 Gy/3–5 fr, fractionated: 39 Gy/13 fr

NR

Median NEST-FS: 16 mo

NR

median PFS 10 mo

Deantoni [35]

2020

Retrospective analysis

2

39/51

47

CT, Bone Scan, Cholin-PET/CT

Bone 100%

44 Gy

100%

95% (at last FU, median 43 mo)

65.7/53.3 (4-year CPFS/BPFS)

Schmidt-Hegemann [64]

2020

Retrospective analysis

5

135/135

16

PSMA-PET/CT, PSMA-PET/MRI

LN 38%, bone or viscera 62%

LN: 50.9 Gy, Bone 56 Gy, Viscera: 93.93 Gy (EQD2, α/β 1.5)

35%

NR

91% at last FU, median 16 month

46% at last FU, median 16 month

Phillips [13]

2020

Prospective randomized phased II study

3

54 (36 SBRT, 18 observation)/73

19

CT, MRT, Bone Scan

LN only 58%, bone-involved 42%

19.5–48 Gy/3–5 fr

0%

NR

98.9% (6-mo)

19 vs 61% (6-mo PFS), 11 vs 50% (6-mo BPFS)

Oehus [25]

2020

Retrospective analysis

5 bone or viscera, no limit for LN

78/185

16

PSMA-PET/CT

LN 69.2%, bone 24.3%, 6.5% viscera

LN: 50.9 Gy, Bone 51.4 Gy, Viscera: 64.7 Gy (EQD2, α/β 1.5)

16.7%

34

NR

55% 1-year bRFS

Koerber [72]

2020

Retrospective analysis

5

86/168

26

PSMA-PET/CT

LN 63%, bone 37%

SBRT: 27–37,5/3–5 fr, 61.2 Gy/34fr

61.9

13.5

90.9% at median 13 mo

85/55% (2/3 year BRFS)

Hurmuz [11]

2020

Retrospective analysis

5

176/353

23

PSMA-PET/CT

LN 43%, bone 35%, both 23%

27 Gy (15–40 Gy)/1–5 fr, 60 (40–78) Gy/25–39 fr

79.5%

NR

93.2% (2-year)

63.1% (2 year BPFS)

Devos [58]

2020

Retrospective analysis

5

191/350

45

CT, Bone Scan, Cholin-PET/CT, PSMA-PET/CT

LN 71%, bone 24%, viscera 6%

30 Gy/3 fr or 62.5/25 fr

61%

66 month

NR

median BRFS 8 month, median CPFS: 30 month

Reverberi [65]

2020

Retrospective analysis

5

37/NR

56

MRI, Cholin-PET/CT

LN 57%, bone 51%, both 19%

45–60 Gy/25 fr, SBRT dose NR/1–5 fr

97.3%

NR

93.9/83.7% (2/5 year)

79.1/55.4% (2/5 year CPFS) 73.3./39.3% (2/5 year BPFS)

Kalinauskaite [12]

2020

Retrospective analysis

5

50/75

34

PSMA-PET/CT

LN 48%, bone 46%, both 4%, viscera 2%

16–28.8 Gy/1–3 fr

30%

2 year ADT-FS: 60.5%

98/96% (1/2 year)

54/22% (1/2 year BPFS)

Deek [27]

2019

Retrospective analysis

5

156/354

25

CT, MRT, Choline-PET/CT, PSMA-PET/CT, NaF-PET/CT, Fluciclovine-PET/CT,

LN 43%, bone 52%, visceral 3%

15–20 Gy/1 fr; 24–36 Gy/3 fr, 30–50 Gy/5 fr

59.6%

27.8

96.1%/93.6% (1/2 year)

52% 1-year BRFS

Deek [44]

2020

Retrospective analysis

5

258/474

25

CT, MRT, Choline-PET/CT, PSMA-PET/CT, NaF-PET/CT, Fluciclovine-PET/CT,

LN 28%, bone 62%, both 10%

15–20 Gy/1 fr; 24–36 Gy/3 fr, 30–50 Gy/5 fr

50.4%

NR

96/93% (1/2 year)

median BPFS 16 month, median DMFS 19 month

  1. BPFS biochemical progression-free survival, CFFS clinical failure-free survival, CPFS clinical progression-free survival, CRFS clinical relapse-free survival, CT computed tomography, DPFS distant progression-free survival, ENRT elective nodal radiation therapy, FDG Fluordesoxyglucose, FFDP freedom from distant progression, FFR failure-free rate, FU follow-up, LN lymph node, MFS metastasis-free survival, MRI magnetic resonance imaging, NaF sodium fluorid, NR not reported, OR oligoreccurent, OP oligoprogressive, PSMA prostate-specific membrane antigen, SBRT stereotactic body radiation therapy, SD single dose, TD total dose