17 The kiel experience on combined external beam- and transrectal sonography guided perineal interstitial brachytherapy treatment for localized prostate cancer

17 THE K I E L EXPERIENCE ON COMBINED EXTERNAL BEAM- AND TRANSRECTAL S O N O G R A P H Y GUIDED PERINEAL INTERSTITIAL BRACHYTHERAPY TREATMENT FOR LOCALIZED PROSTATE CANCER GyOrgy Kov~cs MD, Razvan Galalae MD, Tillmann Loch MD, Peter Rhezak MA, Peter Niehoff MD, Peter Kohr PhD, Hagen Bertermann MD, Bernhard Kimmig MD Interdisciplinary Brachytherapy Center of the University Hospital in Kiel, Arnold Heller Str.9, D-24105 Kiel, Germany Background and Purpose: To evaluate a new therapy protocol for local dose escalation by high dose rate (HDR) brachytherapy for survival, morbidity and prognostic variables in men with localized prostate cancer. Material and methods: The prospectively recorded files of 172 nodal negative men aged in median 69 (mean 68) years with a median follow-up of 63 months (mean 66 months) receiving curatively intended combined high dose rate (HDR) 192 lridium-brachytherapy (BT) and external beam radiation (EBRT) for locally confined prostate cancer were analyzed. Imaging method for local staging was transrectal sonography (TRUS) and CT and/or MRI for nodal involvements. The treatment schedule incorporated 50 Gy conventional fractionated EBRT combined with 2 fractions (after 20Gy and 40 Gy EBRT dose) of 15 Gy TRUS guided perineal interstitial BT in 6-7 weeks. The total Biological Equivalent Dose (BED) for the treatment was calculated as a total dose of 115 Gy regarding to the 15 Gy BT isodose line which covered the peripheral zone of the prostate including 20-40% of that volume which received 20 Gy fraction dose with a total BED of 135 Gy (boost-in-boost strategy). Biochemical failure was defined as by the ASTRO Consensus Meeting. Instead of Gleason Scores (GS) the WHO (Mostofi) System was used (Grade 1 = GS 0 - 4; Grade 2 = GS 5 - 7; Grade 3 = GS 8 - 10). Results: Treatment results were analyzed according to different prognostic groups. G r o u p I (n -- 57): PSA< 10, GS < 6; G r o u p II (n = 24): PSA 10-20, GS < 6; G r o u p III (n = 31): PSA >20, GS < 6; G r o u p IV (n = 18): PSA < 10, GS > 7, Group V (n = 13): PSA 10-20, GS >7; Group VI (n = 29): PSA >20, GS > 7 The median follow-up in the groups were 74, 81,5, 56, 68,5, 75 and 70 months, respectively. In Group I the percentage of T2b-T3 cancers was 70,1% in Group 11: 87,5%, in Group III: 80,6%, in Group IV: 83,3%, in Group V: 84,6%, in Group VI: 86,2%, respectively. The median initial PSA values in the different groups were 6 ng/ml; 14,1 ng/ml; 33,6 ng/ml; 5 ng/ml; 14,6 ng/ml and 38,6 ng/ml. In Group V1 patients with PSA> 40 ng/ml were represented in 50% of the cases. The median WHO grading was listed as in Group I: 2 (GS 5 - 7); in Group 1I: 2 (GS 5 - 7); in Group 111:2 (GS 5 - 7); in Group IV: 3 (GS 8 - 10); in Group V: 3 (GS 8 - 10) and in Group VI: 3 (GS 8 - 10), respectively. Because of lower number of patients (under 25) in the cohort, five years act. clinical failure rate (CF), 5-yr biochemical control (bNED), 5-yrs act. disease free survival (DSF) and 5-yr overall survival (OS) were only calculated for the Groups I, Ill and VI. Act. failure rate was 1,8% for Group I, 12,9% for Group 111 and 34,5% for Group VI. bNED was observed in Group I: 94,7%; in Group 111:67,7% and 38% in Group VI. DFS was 98,2% in Group 1, 87,1% in Group III and 65,5% in Group VI. OS was 82,5% in Group 1, 67,7% in Group III and 62,1% in Group V1. In patients with T2b/T3, GS<6, PSA<10 (n = 39, median PSA 6,4 ng/ml, median Mostofi score 2) we observed a CF of 2,5%; bNED in 92,5%, DFS in 97,5% and OS in 85%. Patients with T2b/T3, GS < 6, PSA >10 < 40 (n = 38, median PSA 18 ng/ml, median Mostofi score 2) showed CF in 15,8%, bNED in 84,2%, DFS in 84,2% and OS in 73,7%. In the cohort of T2bfl'3, GS > 7, PSA < 20 (n = 28, median PSA 8,4 ng/ml, median Mostofi score 3) CF in 21,4%, bNED in 75%, DFS in 78,6% and OS in 71,4% was documented. At the patients with any T, any GS and PSA > 40 ng/ml (n = 26, median PSA 73,6 ng/ml, median WHO score 3) we found CF in 26,9%, bNED in 34,6%, DFS in 73% and OS in 69,2%, respectively. Late Grade 3 radiation toxicity according to the EORTC/RTOG score side effects were observed in 2,3% for the genitourinary and 3,8% for the gastrointestinal system respectively. No Grade tV - V side effects occurred. Conclusion: This results confirm, that local dose escalation by perineal TRUS-guided interstitial HDR brachytherapy is in men with localized prostate cancer an effective treatment. The method is especially suitable for high-risk patients.

15

Prognostic Group

PSA _< 10, GS_<6 PSA 1020, G S < 6 PSA >_ 20,

# Pts

Median Followup (mos)

% TlfF2a

% T2b/T3

Median PSA (ng/ml)

Median WHO Grade

Median Age (years)

57

74

29,9

70,1

6

2 ,

68

Median Nomina i Total Dose (Gy) 70

24

81,5

12,5

87,5

14,1

2

68

70

31

56

19,4

80,6

33,6

2

70

70

18

68,5

16,7

83,3

5

3

69

70

13

75

15,4

84,6

14,6

3

68

70

29

70

13,8*

86,2

38,6

3

70

GS_<6 P S A _< 10, GS > 7 PSA 1020, GS >__7 P S A >~ 20,

5 Yr Act bNED (%)

5 Yr Act DFS (%)

5 Yr Act OS

5 Yr Act Clinical Failure (%) 1,8

94,7

98,2

82,5

12,9

67,7

87,1

67,7

70

34,5

38,5

65,5

62,1

5 Yr Act Clinical Failure

5 Yr Act Biochem Control

5 Yr Act DFS (%)

5 Yr Act OS (%)

(%)

GS>7

*Tlb (n=2) is 1,2% of the complete material (n=172)

Prognostic Group

Tlc/T2a, GS _<6, PSA _< 10 Tlc/T2a, GS _<6, PSA> 10_<20 Tlc/T2a, GS _<6, PSA > 20 < 40 Tlc/T2a, GS >-7, PSA < 10 Tlc/T2a, GS _>7, PSA >10 _<40 T2b/T3, GS _<6, PSA _<10 T2b/T3, GS _<6, PSA > I 0 -<40 T2b/T3, GS >-7, PSA _<20 T2b/T3, GS > 7, PSA > 20 _<40 Any T, any GS, PSA >40

# Pts

Median Followup

%

%

Median PSA

Median WHO Score

Median Age

16

79

6,25

93,75

3,6

2

68

Median Nominal Total Dose 70

3

89

--

100

13,1

2

68

70

3

60

100

23,8

1

69

70

3

95

66

7,6

3

69

70

4

37,5

100

21,2

3

78

70

39

74

62,5

37,5

6,4

2

70

70

2,5

92,5

97,5

85

38

70

42,1

57,9

18,0

2

69

70

15,8

84,2

84,2

73,7

28

63,5

46,4

53,6

8,4

3

68

70

21,4

75

78,6

71,4

12

80,5

58,3

41,7

24,5

3

74

70

26

63,5

69,2

30,8

73,6

3

68

70

26,9

34,6

73,0

69,2

33

16