2. Definition: High-Risk
Standard definition of High-Risk (any one of the
below)
PSA > 20
Gleason > 7
Stage > T2b
Two or three Intermediate-Risk Factors
An even more serious form of High-Risk:
Any Gleason grade 5 (Gleason score 9 or 10)
Seminal vesicle invasion
Pelvic lymph node metastases
3. High Risk Group is Heterogeneous
Big difference between a T1c, Gleason 8, PSA 6
and a T3, Gleason 7, PSA 40.
The differing profile of High Risk disease in
research studies is highly era dependant and
continues to be a problem in comparing
treatment outcomes today.
Trend for High Risk category today is lower
volume disease but high grade
4. High Risk
Approximately 15% of the 220,000 men who are
diagnosed annually (33,000 men) are High-Risk
Cancer specific mortality at 10 years for High-Risk
disease averages between 5% and 15%
There is some consensus among experts about
treatment:
1. Treat, don’t observe (except the very elderly or infirm)
2. Radiation plus testosterone inactivating
pharmaceuticals (TIP) is generally a better treatment
than surgery (except perhaps in men who have a high
Gleason but very low volume disease)
5. Staging Studies: High Risk
Considered standard:
Bone Scan to evaluate for possible bone metastasis
CT scan (or MRI ) of abdomen and pelvis to evaluate for
possible pelvic node metastases
Logical but still not considered standard: Endorectal
MRI to evaluate for possible seminal vesicle invasion
(scan quality varies depending on equipment and
physician experience )
6. What to Do with Scan Results that
Are Considered Ambiguous?
Suspicious bone scan findings can be further
evaluated with MRI or with CT directed biopsy
Suspicious pelvic node findings can be evaluated
with ProstaScint, experimental PET scans, CT
directed needle biopsy or laparoscopic surgery
Suspicious endorectal MRI findings suggesting
seminal vesicle invasion can be evaluated with
color doppler or endorectal MRI directed biopsy
7. Surgery for Gleason 8-10?
Epstein, Urology 76:715, 2010
9300 men with median:
PSA of 7.5 and stage T2
80% recurrence rate at 15 years
70% had extra capsular disease
An even worse outcome was associated with any:
Gleason grade 5
Seminal vesicle invasion
Positive lymph nodes
Take home message: Surgical cure rates are low with
high Gleason score when there is a palpable
abnormality on digital rectal examination
9. Outcome after Surgery in Men
with
High-Risk is Improved with TIP
Men with High-Risk:
Two years of TIP consisting of Zoladex plus Casodex
resulted in surprisingly low relapse rate in 481 men with
High-Risk disease (Dorff, JCO 29:2040, 2011)
Relapse rate @ five years was only 7.5%
Men with Positive Nodes:
Immediate TIP was better than TIP started at relapse in
men with positive nodes at surgery (Messing, NEJM, 341:1781,
1999)
Mortality @ 7 years: 15% vs. 40%
10. Pelvic XRT after Surgery in Men
Found Node Positive from Surgery
Briganti, Eur Urol 2011
364 men node positive after surgery
117 men had TIP plus pelvic radiation vs.
247 men had TIP without radiation
10-year cancer specific survival
86% with TIP plus XRT to pelvic nodes
70% with TIP alone
11. Is Surgery Appropriate for High Risk?
Please consider the following:
If cure rates with surgery alone are poor…
If men do better after surgery with the addition
of TIP….
If men do better after surgery with pelvic node
radiation…..
Why not proceed straight to radiation and skip
the surgery ?
12. Surgery Vs. Radiation for High-Risk
Arcangeli, IJROBP 75:975, 2009
162 men treated with EBRT plus TIP
9 months of testosterone deprivation started 2 months
before xrt
80 gy without node treatment
122 men treated with radical prostatectomy
Radiation patients had higher Gleason scores and
clinical stage that surgery patients
3-year relapse rate was 13% for the radiation patients
and 30% for the surgery patients
13. Rationale for seed implant boost
Higher dose, more conformal radiation treatment is
attained with seed implant compared to external
beam radiation alone
Studies incorporating seed implant boost show
excellent relapse free survival rates
15. Radiation Dose From Seeds in EBRT
Equivalent Doses
Prostate
Typical IMRT ≈ 100 Gy EBRT
high dose equivalent
78 – 81 Gy
Area of
Prostate
Receiving
150+ Gy
EBRT
equivalent
16. Seeds + EBRT
Dose vs. Risk Grouping
Low Risk Disease High Risk Disease
(standard)
(seeds + EBRT)
(inadequate)
(standard for
seeds alone)
552 patients
2,188 patients
p < 0.0001
(inadequate)
Achieving high dose more important for *Stone NN et al, IJROBP
High Risk disease than for Low risk Vol. 69, #5, 1472, 2007
17. Cure Rates: Seeds for High-Risk
# TIP Cure Follow Reference
Pts. Rate Up
190 6 mo. 95% 8 yr. Merrick, IJROBP 61:32, 2005
243 ½ 6 m0. 88% 10 yr. Bittner, IJROBP 72:433, 2008
107 no 63% 10 yr Demanes, AJCO 32:342, 2009
18. Very High Risk Treated with
Seeds + EBRT + TIP*
131 patients, median age 68 yr.
T3
PSA > 40
Gleason 10
Gleason 8-9 with >50% + bx cores,
Gleason 8-9 with PSA > 20
12 year results
Overall survival 61%
Cause-specific survival 88%
PSA progression free 71%
Cause of death
Prostate cancer 8.3%
Heart disease 22.2%
*Bittner N, Merrick GS, Butler WM, et al.
Brachytherapy 11(2012) 250-255
19. Relapse Rates: High-Risk
EBRT, Seeds & ADT
20
20 16
16 45
45
109
109
Brachy
19 18
19 18 4
4
38 22
22
108
108 EBRT & ADT
17
EBRT & Seeds
Treatment Success
43 32
43 32 37
37
34
34
44
47
47 Hypo EBRT
44
9 41
9 41 22 104
48 104
36
36 48 10
10 42
11 12 42 24
12 8 24
25
25 8
101
101
106
106 33 21
33 21 5
5
39
39
EBRT
103
103
35
35
11
11
7 6 26
7 6 26 Surgery
31 30
Protons
46 31 30
46 107
107
102 15
102 15 HDR
105
105
EBRT Seeds +
r g or P AS P %
23 29
29
← Years from 23
Treatment 49
49 ADT
→ Robot RP
• Prostate Cancer Results Study Group
• Numbers within symbols refer to references
19
Prostate Cancer Center of Seattle
20. Relapse Rates: High-Risk
>40 months follow-up or less than 100 patients
65
81 20
20 16
16 45 109
109
Brachy
19 18 45
80 19 18 4
74 4 108
108 EBRT & ADT
78 38 22
22
67
67 17
55 75 EBRT & Seeds
72 54 85 43 76
43 37
37
72 54 34
34 44 32
32
47
47 Hypo EBRT
66 9 41
66 9 41 68 44
2 57 104
71 6436 68
71 6436
79 48 59
48 59
2
10
104
10 42
42
50
50 56 11
56 12
12 24
24
53 25 8 61
8 61
25 89
89
101
101
EBRT 62 106
62 106
70
70
33 21
33 21 5
39
5
39
11
11 60
60
103
103 83 7 82 26
83 7 82 26
35
35 63 66
Protons
ss ecc uS t ne maer T
52 63
52 84
84
73 31 30 58
77 46 73
46
31 30 58
88
88
86 87
86 87
107
107
102 15
102 15
HDR
t
51
51 105
105
EBRT Seeds +
r g or P AS P %
23 29
Surgery
29
← Years from 23 Treatment
69
69 49
49
ADT
→ Robot RP
• Prostate Cancer Results Study Group HIFU
• Numbers within symbols refer to references
02/23/13 20
Prostate Cancer Center of Seattle
21.
22. Rationale for Pelvic Radiation
Metastatic disease represents the most dangerous
component of the cancer
Historically, pelvic radiation is incorporated as standard in
all randomized prospective trials of High-Risk disease
One randomized study by Mack Roach showed improved
disease free survival at 5 years with pelvic xrt
Another randomized study by Pascal Pommier showed no
benefit
Modern IMRT radiation is far less toxic that older
radiation technology
23. Hormones Plus Node Radiation
Roach, IJROBP 69:646, 2007
1500 patients randomized between no node radiation
and 50 Gy of node radiation. Dose to prostate was 70
Gy. Men were also randomized between TIP starting
two months before radiation and continuing for four
months vs. starting TIP at the end of radiation (also
for four months)
Patients: Median PSA was 22, 73% of men had
Gleason 7 or more, 2/3 of men were stage T2c, T3 or
T4
Conclusion: Node radiation improved cure rates.
However, the improvement was only seen when TIP
was started 2 months before radiation
24. Pelvic Node Radiation Ineffective?
Pommier, JCO 25:5366, 2007
444 patients
Pelvic node radiation 46 Gy (instead of 50Gy)
Small radiation field than the Roach study
Initial dose to prostate only 66 Gy
50% of study participants had calculated risk of node
metastases of less than 15%
Patients: Median PSA 16, 50% Gleason 6 or less, 25% stage
T3 (the rest were T1 or T2)
Conclusion: No difference in cure rates at 5 years but
study was seriously underpowered to detect a difference
25. Toxicity from Node Radiation?
Deville, IJROBP 78:763, 2010
30 patients treated with IMRT 79 Gy
30 patient treated IMRT 79 Gy and 45 Gy to pelvis
At 24 months no “late” GI or GU toxicity
Deville, IJROBP 82:1389, 2012
31 patients IMRT 70.2 Gy (to fossa after surgery)
36 patients IMRT 70.2 to fossa & 45 Gy to pelvis
No significant difference in “late” toxicity at 25 months
26. Calculating Risk of Nodes
Yu, IJROBP 80:69, 2011
Mack Roach has proposed that only men with more
than a 15% risk of node metastases should be
considered candidates for node radiation
The % risk of nodes involvement can be calculated as:
(Gleason score minus 5) x (PSA/3 +1.5 x T stage)
where T = 0, 1 or 2 for T1c, T2a, and T2b or T2c.
This is the so called Yale formula which has
supplanted the Roach formula and the Nguyen
formula due to enhanced accuracy
Note: Formula does not incorporate other important
prognostic info such as % biopsy or imaging results
27. Not All Node Radiation Equal
Lawton, IJROBP 74:377, 2009
Two different clinical cases distributed to 14 radiation
oncologists with expertise in genitourinary oncology
Conclusion, “Significant disagreement exists in the
definition of…. pelvic nodal radiation therapy among
GU radiation oncology specialists”
Consensus meeting October 2007 to develop a
clinical target volume (CTV) for node radiation by 10
GU radiation specialists.
Access to their conclusions was published in the same
journal (Lawton, IJROB 74:383, 2009)
28.
29. Longer Duration of TIP is Clearly Better
1. 4 months Zoladex/Flutamide vs. none (Pilepich, IJROBP 50:1243, 2001)
Cancer death @ 8 years: 23% vs. 31%
2. 36 months of Zoladex vs. none (Bolla, Lancet 2010)
Cancer death @ 10 years: 10% vs. 30%
3. 24 months of Zoladex vs. 4 months of Zoladex plus
Flutamide: (Horwitz, JCO 26:2497, 2008)
Cancer death @ 10 years: 11% vs. 16%
30. Rationale for Casodex or Flutamide
Nanda, IJROBP 76: 1439,2010
628 High-Risk men treated with:
Beam radiation
Brachytherapy boost
Average of 4 months hormone blockade
401 men received Lupron alone whereas 227 men were
treated with a combination of Lupron plus antiandrogen
Outcome at 5 years: Men receiving Lupron plus
antiandrogen had a significantly lower rate of prostate
cancer mortality
31. Adjuvant Chemotherapy
Rationale: Treat micro-metastatic disease while still
vulnerable to eradication
Proven benefit in other tumor types such as breast,
colon and lung cancer
Chemotherapy options limited to two drugs: Taxotere
or Mitoxantrone
Preliminary trials in prostate cancer suggest a
possible benefit
32. Adjuvant Mitoxantrone
Wang, BJU 86:675, 2000
38 men with locally advanced disease
All given with Lupron / Flutamide indefinitely
19 men randomly allocated to 4 cycles of
mitoxantrone (this is the only randomized trial of
adjuvant chemotherapy in existance)
Kaplan-Meier survival curve shows significantly
prolonged survival in the men administered
mitoxantrone (next slide)
34. Adjuvant Taxotere
Kibel, J Urol 177:1777, 2007
77 men treated with surgery most who had seminal vesicle
invasion and high Gleason scores
The median time to relapse for this group of patients based
on their stage, Gleason score and PSA was predicted to be
10 months by a Kattan Nomogram
All 77 men were administered weekly Taxotere for 6 mo.
Actual median time to relapse was improved by 50% (to
15.7 months)
35. Radiation + Hormones + Taxotere
DiBiase IJROP 81:732,2011
42 patients
75 % grade 4 + 3 or higher
Median PSA 17.8
Treatment
Pelvic radiation
Brachytherapy boost
Lupron for two years
Weekly Taxotere for 3 months
Outcome: 70% disease free after 7 years
36. Conclusion: The Best Treatment
for High-Risk is Multimodality
Therapy
TIP for two years, to be started a couple
months before XRT
IMRT to prostate and pelvic nodes when
calculated risk of nodes is > 15%
Seed implant boost to prostate
Palladium or Iodine permanent seeds
HDR temporary seeds (for SV invasion?)
Adjuvant chemotherapy is still considered
investigational
Notas do Editor
This sets the theme for this talk which is multimodality therapy is standard and that surgery is an inferior approac
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Critz, F et al. 10-year Disease Survival Rates After Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation Methodology. J Urology 2004;172:2232-2238. 9. Galalae, R et al. Long-term Outcome by Risk Factors Using Conformal High-Dose-Rate Brachytherapy (HDR-BT) Boost with or without Neoadjuvant Androgen Suppression for Localized Prostate Cancer . Int J Radiat Oncol Bio Phys 2004;58(4):1048-1055. 10. Kollmeier, M et al. Biochemical Outcomes After Prostate Brachytherapy with 5-year Minimal follow-up: Importance of patient Selection and implant Quality. Int J Radiat Oncol Bio Phys 2003;57(3):645-653. 11. Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Biol Phys 2003;57(4):915-928.(PSA:4-10,GS:2-6,>70 Gy) 12. Kuban, D et al. Long-Term Results of the MD Anderson Randomized Dose-Escalation Trial for Prostate Cancer. Int J Radiat Oncol Bio Phys 2008;70(1):67-74. 13. (Open) 14. 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(EBRT & Seeds) 20. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1):32-43. (EBRT, Seeds, ADT) 21. Mian, B et al . Outcome of Patients w/ Gleason score 8 or Higher Prostate Cancer following Radical Prostatectomy alone . J Urology 2002;167:1675-1680. 22. Pellizzon, A et al . The Relationship Between the Biochemical Control Outcomes and the Quality of Planning of HDR as a Boost to External Beam Radiotherapy for locally and locally advanced Prostate Cancer using the RTOG-ASTRO Phoenix definition. Int J Med Sci 2008;5:113-120. 23. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1):129-136. (EBRT) 24. Potters, L et al. 12-Year Outcomes Following Permanent Prostate Brachytherapy in Patients With Clinically Localized Prostate Cancer. J Urology 2005;173:1562-1566. 25. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1):129-136. (RP) 26. Sylvester, J et al. Ten Year Biochemical Relapse Free Survival After External Beam Radiation and Brachytherapy for Localized Prostate Cancer: The Seattle Experience. Int J Radiat Oncol Bio Phys 2003;57(4):944-952. 27. (Open) 28. (Open) 29. Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups. Int J Radiat Oncol Bio Phys 2006; 65(4):975-981. 30. Ward, J et al. Radical Prostatectomy for Clinically Advanced (cT3) Prostate Cancer since the advent of PSA testing: 15 year outcome. BJU Int 2005; 95:751-6. 31. Zelefsky, M et al. Multi-Institutional Analysis of Long-Term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation. Int J Radiat Oncol Bio Phys 2007;67(2):327-333. 32. Zelefsky, M et al. Long Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer. J Urology 2006;176:1415-19. (81 Gy) 33. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol Bio Phys 2008;71(4):1028-33. (81 Gy) 34. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor Control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol bio Phys 2008;71(4):1028-33. (86 Gy) 35. Zelefsky, M et al. High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the Outcome of Localized Prostate Cancer. J Urology 2001;166:876-881. (75 Gy) 36. Zelefsky, M et al. High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the Outcome of Localized Prostate Cancer. J Urology 2001;166:876-881. (81 Gy) 37. Dattoli, M et al. Long-term Outcomes After Treatment with Brachytherapy and Supplemental Conformal Radiation for Prostate Cancer Patients Having Intermediate and High-Risk Features. Cancer 2007;110(3):551-555. 38. Moyad, M et al. Statins, especially Atorvastatin, may Favorable Influence Clinical Presentation and Biochemical Progression-free Survival after Brachytherapy for Clinically Localized Prostate Cancer. Urology 2005;66(6):1150-1154. 39. Zelefsky, M et al . Long Term Outcome Following Three dimensional Conformal/IMRT for Clinical Stage T3 Prostate Cancer. Eurr Urol 2008; 53:1172-79. 40. (Open) 41. Galalae R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer . Strahlenther Onkol 2006;182(3):135-141. 42. Demanes, DJ et al. Excellent Results from High Dose Rate Brachytherapy and External Beam Radiation Therapy for Prostate Cancer are Not Imroved by Androgen Deprivation. Amer J Clin Oncol 2009;32(4):342-347. 43. Stock, R et al. Outcomes for patients with High-Grade Prostate Cancer Treated with a Combination of Brachytherapy, EBRT and Hormone therapy. BJU Int 2009;104:1631-1636. 44. Stone, N et al . Local Control following Permanent Prostate Brachytherapy: Effect of High Biologically Effective Dose on Biopsy Results and Oncologic Outcomes. Int J Radiat Oncol Bio Phys 2010;7 6(2):355-360. 45. Bittner, N et al. Whole Pelvis Radiotherapy in Combination with Interstitial Brachytherapy: Does Coverage of the Pelvic Lymph Nodes Improve Treatment Outcome in High Risk Prostate Cancer? Int J Radiat Oncol Bio Phys 2010;76(4):1078-1084. 46. Rubio-Briones, J et al . Metastatic Progression, Cancer Specific Mortality and Need for Secondary Treatments in Patients with Clinically High Risk Prostate Cancer Treated Initially with Radical Prostatectomy. Actas Urologicas Esanolas 2010; 34(7):610-617. 47. Dattoli, M et al . Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Beam Irradiation and Brachytherapy. J Oncology 2010;2010(Article Id 471375):6 pages. 48. Menon, M et al . Biochemical Recurrence Following Robot Assisted Radical Prostatectomy: Analysis of 1384 patients with a median 5 year follow-up. Eurr Urol 2010;58:838-46. 49. Pierorazio, P et al. Long Term Survival after Radical Prostatectomy for Men with High Gleason Sum in Pathologic Specimen. Urology 2010;76(3):715-21. 101. Deger, S et al . (Germany) High Dose Rate (HDR) Brachytherapy with Conformal Radiation Therapy for Localized Prostate Cancer. Eurr Urology 2005;47:441-448. 102. Magheli A et al . (Johns Hopkins) Importance of Tumor Location in Patients with High Preoperative PSA Levels ( greater than 20 ng/ml treated with Radical Prostatectomy . J Urology 2007;178:1311-15. 103. Kupelian P, et al. Improved Biochemical Relapse-Free Survival With Increased Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in 1994 and 1995. Int J Radiat Oncol Bio Phys 2005;61(2):415-419. 104. Sylvester, J et al. 15-Year Biochemical Relapse Free Survival in Clinical Stage T1-T3 Prostate Cancer Following Combined External Beam Radiotherapy and Brachytherapy: Seattle Experience. Int J Radiat Oncol Bio Phys 2007;67(1):57-64. 105. Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients Treated with I-125 Permanent Prostate Brachytherapy. Int J Radiat Oncol Biol Phys 2010; 76(5):1433-1438. 106. Hsu, C et al . 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1 st Group References: 1. Bahn, D et al. Targeted Cryoablation of the Prostate:7-year Outcomes in the Primary Treatment of Prostate Cancer. Urology 2002;60(Supp 2A):3-11. 2. Burri, R et al. Young Men have Equivalent Biochemical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer. Int J Radiat Oncol Bio Phys 2010;77(5):1315-21. 3. (Open) 4. Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008;72(2):433-440. 5. Boorjian, S et al. Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urology 2008;179:1354-1361. 6. Carver, B et al. Long Term Outcome following Radical Prostatectomy in Men with Clinical T3 Prostate Cancer. J Urology 2006;176:564-568. 7. Cohen, J et al. Ten-Year Biochemical Disease Control in Patients with Prostate Cancer Treated with Cryosurgery as Primary Therapy. Urology 2008;71(3):515-518. 8. Critz, F et al. 10-year Disease Survival Rates After Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation Methodology. J Urology 2004;172:2232-2238. 9. Galalae, R et al. Long-term Outcome by Risk Factors Using Conformal High-Dose-Rate Brachytherapy (HDR-BT) Boost with or without Neoadjuvant Androgen Suppression for Localized Prostate Cancer . Int J Radiat Oncol Bio Phys 2004;58(4):1048-1055. 10. Kollmeier, M et al. Biochemical Outcomes After Prostate Brachytherapy with 5-year Minimal follow-up: Importance of patient Selection and implant Quality. Int J Radiat Oncol Bio Phys 2003;57(3):645-653. 11. Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Biol Phys 2003;57(4):915-928.(PSA:4-10,GS:2-6,>70 Gy) 12. Kuban, D et al. Long-Term Results of the MD Anderson Randomized Dose-Escalation Trial for Prostate Cancer. Int J Radiat Oncol Bio Phys 2008;70(1):67-74. 13. (Open) 14. 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(EBRT & Seeds) 20. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1):32-43. (EBRT, Seeds, ADT) 21. Mian, B et al . Outcome of Patients w/ Gleason score 8 or Higher Prostate Cancer following Radical Prostatectomy alone . J Urology 2002;167:1675-1680. 22. Pellizzon, A et al . The Relationship Between the Biochemical Control Outcomes and the Quality of Planning of HDR as a Boost to External Beam Radiotherapy for locally and locally advanced Prostate Cancer using the RTOG-ASTRO Phoenix definition. Int J Med Sci 2008;5:113-120. 23. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1):129-136. 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