2. R
I Royal: Advanced
A Indigo: PSA Relapse
T Azure: High-Risk
S Teal: Intermediate-Risk
Sky: Low-Risk
A
Abnormal PSA
3. Diagnosing a Shade of Blue
* One core > 50% replaced with cancer bumps to Teal
** Two yellow boxes bumps Teal to Azure
*** Any rising PSA with a low testosterone bumps to Royal
ECE = Extra-capsular Extension, SV = Seminal Vesicle, PN = Pelvic node
4. Intermediate Risk
Standard definition of Intermediate-Risk
PSA of ten to twenty
Gleason score of seven
Moderate sized nodule (stage T2b) involving 2
quadrants of the prostate
High-Risk rather than Intermediate-Risk
Two or three factors instead of one
More than 50% of core biopsies positive
MRI or Color Doppler Ultrasound showing extra-
capsular or seminal vesicle invasion
5. Intermediate Risk—Most Challenging
Shade Due to Multiple Options
Brachytherapy Seeds
Permanent
Temporary
IMRT—Low vs. high fractions (Cyberknife)
Proton Therapy
Surgery: The “Open” traditional style or robotic
Active Surveillance
Hormone therapy—TIP
7. Factors Related to Treatment
Patient factors:
Advanced age
Comorbidity
Previous abdominal surgery
Sexual factors:
Potency
Libido
Partner’s function and libido
Prostate factors:
Size
Preexisting urinary symptoms
History of TURP
8. Multi-Parametric Endorectal MRI
Minimum Requirements for Adequate Imaging:
Performed at a center doing a large number of
prostate imaging studies
Films read by experienced radiologists with training
in MRI interpretation of prostate radiology
State-of-the-art equipment and technique
Three Tesla magnet
Intravenous contrast
Diffusion
Spectroscopy?
18. Seed Monotherapy: Teal
100 33
33 23 13
14
14 23 13 37
37
90 44
44
16
16
39
39
6 12
6 12 42
42
80 17
17
BrachyAlone
Seeds
Surgery
70 29
29
EBRT
11
11 46
46 CRYO
60
HIFU
ss ecc uS t ne maer T
50
er g or P AS P %
t
← Years from Treatment →
40
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
•Numbers within symbols refer to references
02/23/13 18
BJU Int, 2012, Vol. 109(Supp 1) Prostate Cancer Center of Seattle
19. 5-Year Cure Rate Depends on Dose
Intermediate-Risk
United Kingdom (Bottomley, IJROBP 76:50, 2010)
88% with D90 > 140 Gy
78% with D90 < 140 Gy
New York (Zelefsky, IJROBP 67:327, 2007)
93% with D90 > 130 Gy
76% with D90 < 130 Gy
Seattle (Wallner, IJROBP 76:349, 2010)
98% with BED > 116 Gy
86% with BED < 116 Gy
20. Seeds Plus EBRT Plus TIP
Stock, IJROBP 75:16, 2009
558 men with Intermediate-Risk
One or more intermediate risk factors
6 months of hormone therapy
10-year cure rate:
92% with BED > 150 Gy
63% with BED < 150 Gy.
21. Urinary Damage after 1 Year
Incidence of urinary problems: (Crook, J Urol 179:141, 2008)
Flare of AUA of > 5 points and > 15 occurred in 23% and
lasted for a median of 3 months
Urinary retention requiring catheter: 3.4%
Stricture: 1.7%
Treatment with TURP: 0.4%
Dependence on ongoing catheterization: 1%
Moderate to severe urinary urgency 6.4% but only 1%
failed to improve with medication (anticholenergics)
83% percent of men who were potent prior to seed
retained potency after five years (Crook, IJROBP 80:1323, 2011)
22. Ejaculatory Function after Seeds
Huyghe, IJROBP 74:126, 2009
Maintained ejaculations: 81%
New onset of reduced volume: 50%
Development of dry ejaculation: 19%
New onset painful ejaculations: 17%
New onset of inability to achieve orgasm: 9%
31. Various Available HDR Monotherapy Protocols
Dose per Number of Total Number of
Treatment Treatments Dosage Implants
XRT
7.25 Gray 6 43.5 2
9.5 Gray 4 38 1
10.5 3 31.5 1
13 2 26 1
Bladder and Rectal Dose Maximum Limited to ~
80% Prescription Dose Results in Low
Complication Rates
32. Five-Year Cure Rates with
EBRT & HDR Boost
Seattle, Mich., Germany (Galalae, IJROBP 58:1048, 2004)
87% no TIP
91% with TIP
Long Beach, Ca (Syed, J Urol 177:123, 2007)
90% with or without TIP
Memorial Sloan Kettering (Zelefsky, Brachytherapy 9:313, 2010)
100% with or without TIP
UCLA (Demanes AJCO 32:342, 2009)
86% without TIP (7 year follow up)
33. Grading System for Delayed Radiation Toxicity
Gastrointestinal (GI)
Grade 2: Moderate diarrhea and colic requiring medication,
> 5 BM daily, excess rectal mucus or intermittent bleeding
Grade 3: Obstruction or bleeding requiring surgery
Grade 4: Necrosis/perforation fistula
Genitourinary (GU)
Grade 2: Moderate urinary frequency requiring medication.
Intermittent use of 1 or fewer pads
Grade 3: Severe frequency and dysuria, frequent hematuria,
regular use of 2 or more pads or self-catheterization
Grade 4: Scarred bladder with restricted capacity, severe
bleeding or permanent catheter
34. Grade 2 Grade 3 Grade 4
Lower Gastrointestinal 5 (2%) 0 (0%) 0 (0%)
Genitourinary 15 (7%) 14 (6.7%) 2 (1%)*
No known grade 4 complications ~ 2000 patients treated since this series
reported
All 7 cases incontinence and both G4 were associated with TUR
Demanes et al AJCO 2009 V32(4)p342
39. Risk of Proctitis “Rectal Burn”
1-2 percent with modern techniques at a
center of excellence
Worse with anticoagulation (Choe,
IJROBP 76:755, 2010)
Reduced by collagen injection (Noyes,
IJROBP 82:1918, 2012)
40. Accelerated IMRT
2.5 Gy in 5 weeks (Kupelian, IJROBP 68:1424, 2007)
85% cure rate at 5 years
3.1% grade 2 rectal toxicity
5.1% grade 2 urinary toxicity
3.1 Gy in 4 weeks (Lock, IJROB 80:1306, 2011)
25% grade 2 and 3% grade 3 rectal toxicity
14% grade 2 and 5% grade 3 urinary toxicity
42. Study of Side Effects: IMRT vs. Proton
Sheets, JAMA 307:1611, 2012
Study evaluated the incidence of GI, urinary, sexual
function and the need for further cancer therapy in
6600 men treated with IMRT and 684 men with
Proton between 2002 and 2007
IMRT was associated with a lower incidence of
gastrointestinal morbidity compare to Proton
There was no difference between the two treatments
in sexual or urinary function
43.
44. Robotic Prostatectomy
Computer enhanced
Surgeon operates at the
console within a 3D view
Bedside surgical assistant
is next to the patient
Instruments move like a
human wrist (↑ dexterity
and precision)
45. Surgeon Directs Instruments
The surgeon’s
hands are placed
in special devices
that direct the
instrument
movement
47. Robotic vs. Standard Surgery in 2700 Men
Good:
Shorter hospital stays (1.4 vs. 4.4 days)
Slightly less complications (30 vs. 36%)
Not so Good:
Higher likelihood of needing salvage radiation therapy
(28 vs 9%)
More urethral strictures (40% more likely)
Hu, Jim et al. Journal of Clinical Oncology, May 2008
48. Urinary Continence
Surgeon 12 mo
Pat Walsh (Open) 93%
Ahlering (Robotic) 94%
Shalhav (Robotic) 84%
Lee (Robotic) 90%
49. Artificial Sphincter
(Backup Treatment for Incontinence)
Kim, J Urol 179:1912, 2008
124 men monitored for 6 ½ years
Complication rate was 37%
Mechanical failure 23%
Erosion 8%
Infections 6%
Degree of incontinence
No pads 27%
One pad 52%
Two or more 15%
50. Trifecta: Two Years After Surgery
Open Surgery (Scardino, J Urol 179:2207, 2008)
50% in 58 year old
25% in 65 year old
Robotic Surgery (Shikanov, Urology 74:619, 2009)
44% in 58 year old
52. “Watching” Palpable Disease
Connecticut study: 20-year death rate of men
diagnosed in the 1970’s was 7%
JAMA 2005
Swedish study: 15-year death rate of men with
well-differentiated prostate cancer was 2.5%
JAMA 1997
53. Active Surveillance vs. Surgery
PIVOT: Intermediate Risk
Prospective, randomized trial starting 1994
364 men had surgery and 367 men active surveillance
Median follow up of 10 years
Mean age = 67 and mean PSA = 10
Gleason was 6 or less in 70%
No difference in cancer mortality at 10 years in men
with Intermediate-Risk
Final publication of results still pending
54. Surgery Vs. “Watching”
Bill-Axelson, New England Journal Medicine
Randomized prospective trial 695 men
Mean PSA 12.8
75% stage B (palpable nodule)
25% Gleason 7 (6% with Gleason >8)
Cancer detected by DRE, not PSA
55. Surgery vs. “Watching”10-Year
Results
Bill-Axelson, NEJM 364:1708, 2011
Surgery “Watching” Risk
Reduction
Cancer 90% 85% 5%
Survival
56. Active Surveillance = Watchful Waiting
Active Surveillance Watchful Waiting
Aim Individualize therapy Avoid treatment
Monitoring Aggressive Lax
Indications for PSA increase, changes Cancer symptoms
treatment on ultrasound or biopsy such as bone pain
Treatment timing Early Late
Treatment intent Cure Symptom control
57. “Benefit” of Surgery Restated
Intermediate risk or
High Risk disease
20 men operated
“Watching” not Active
Surveillance
= to save 1 life 10
years later
No early treatment for
a rising PSA
58. “Benefits” of Surgery beyond Survival:
Fifteen Year Outcome
Bill-Axelson, NEJM 364:1708, 2011
Event Surgery Watchful Chance for
Waiting Difference
Cancer 15% 21% 1 of 17
Death
Metastases 22% 33% 1 of 9
Hormone 40% 63% 1 of 4
Therapy
Biggest risk of a man doing “nothing” compared to doing surgery
was that there was a 23% greater chance of requiring hormone
therapy over the next 15 years when he skipped surgery
59.
60. Testosterone Inactivating
Pharmaceuticals
Advantages Disadvantages
Total body anti-cancer Not curative
effect
Wide ranging side effects
Mostly reversible side
affecting libido, strength,
effects body habitus & emotions
Acts like a cancer stress Long-term effects on
test libido and erectile
PSA nadir
function?
Biopsy outcome
61. One Year TIP: Intermediate Risk
Scholz The Prostate 2012
30 patients
14% had significantly positive biopsy after 12 months
After 7.25 years median follow up:
11 men had local therapy with seeds, IMRT or cryo
4 men had a second round of TIP
15 men required no further therapy
Only factor predicting progression was a small prostate
No men having local therapy had a PSA relapse
One man developed metastasis
No prostate cancer deaths
63. 8-10 Year Cancer Specific Mortality
10 years: 10,500 men (Kibel, J Urol 187:1259, 2012)
Surgery: 1.8%
External beam: 2.9%
Seed implant: 2.3%
8 years: 1019 men Interm. Risk (Zelefsky, JCO 28:1508, 2010)
Surgery: 1.9%
External beam 4.5%
Comment: Delay of salvage treatment with radiation patients
64. Relapse Rates of Different Treatments
18,000+ prostate studies were published between
2000 and 2010
848 of those studies featured treatment results
140 of those met the criteria to be included in
this review study.
Some treatment methods are under-represented
due to failure to meet criteria
02/23/13 64
65. INTERMEDIATE RISK RESULTS
100
14 33 13
13 37 Robot RP
14 33 37
31
31 35
35
34
34
90 1544
+
+ Seeds + HT
1544
38 40
36 45
36 45 4
4 38 32 40
32 EBRT & Seeds
77 39
39
12
12 16
16 42
42
80 43
43 3
3 17
17
Hypo EBRT
6 5
18
18 28
28 Brachy
Seeds Alone
6 5 9
9
7 25
7 25
29
29 Surgery
70 41
41
11
2
EBRT
2
10
10 11
11 46
46 CRYO
60
HIFU
ss ecc uS t ne maer T
20 8
20 8
HDR
50
er g or P AS P %
t
EBRT, Seeds + HT
← Years from Treatment → 21
21
Protons
40 22
22
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
65
66. INTERMEDIATE RISK
31
14 33
14 33
35
13
35
13 37
37 EBRT + Seeds Robot RP
31
34
34
1544
+
+ Seeds + HT
1544
38 40
36 45
36 45
77 39
39
4
4 38
Seeds Alone
32 40
32 EBRT & Seeds
12
12 16
16 42
42
43
Hypo EBRT
43 3
3 17
17
18
18
6 5
6 5
28
28 Seeds Alone
9
9
29
29
7 25
7 25 41
41
11
2
2
10
10 11 46
11 46
ss ecc uS t ne maer T
20 8
20 8
HDR
er g or P AS P %
t
EBRT, Seeds + HT
← Years from Treatment → 21
21
Protons
22
22
66
66
67. Intermediate Risk
Grimm BJU 109:22, 2012
1
15 40
24
Brachy
0.9 8
23
2
17 37
0.8 12 22
Percentage 4 40
16
Surgery Brachy
0.7
Relapse 36 12
34 32
Free 0.6 31
43 8
Surg
0.5
no ss er g or P %
0.4
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Years after Treatment
i
69. Sexual Distress of 625 Spouses
Sanda, NEJM 358:12, 2008
Type of Median Age of % of Partners
Treatment Patient Distressed
Surgery 59 44%
Radiation 69 22%
Seed Implants 65 13%
70. QOL after 5 years: Surgery vs. Seeds
Crook J Clin Onc 29:362, 2010
Seeds implants showed significantly better:
Urinary function
Sexual function
Overall patient satisfaction
There was no difference in bowel function
76. 3- Year Outcome Depends on Baseline Function
Chen JCO 27:3916, 2009
77. Teal: Conclusions
Mortality risk is very low, but not zero
Local therapy is effective but potentially toxic
Local treatment options have similar survival so quality
of life considerations are paramount
Quality of life clearly favors seed implants over surgery
Testosterone Inactivating Pharmaceuticals enable men
to temporize but they also have notable side effects
Treatment improvements in the future will probably
consist of improved imaging mated with focal therapy
Editor's Notes
1 st Group References: Bahn, D et al. Targeted Cryo-Ablation of the Prostate:7 yr Outcomes in Primary Treatment of Prostate Cancer. Urology 2002 ; 60(Supp 2A):3-11. 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. 3 Critz, F et al. 10-Year Disease Free Survival Rates after Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation and Methodology. J Urology 2004;172:2232-2238. 4 Galalae, R et al . Long-term Outcome by Risk Factors Using Conformal high Dose Brachytherapy Boost with or without Neoadjuvant Androgen Suppression for Localized Prostate Cancer. Int J Radiat Oncol Bio Phys 2004; 58(4):1048-1055. 5 Klein E , et al . Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy . Urologic Oncology 2009;27(1):67-71. (RP) 6 Klein E , et al . Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy . Urologic Oncology 2009;27(1):67-71. (Seeds) 7 Kupelian, P et al. Imporved biochemial Relapse-Free Survival With Increased External Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in patients in 1994 and 1995. Int J Radiat Oncol Bio Phys 2005;61(2):415-419. 8 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 Bio Phys 2003;57(4):915-928. 9 Kupelian, P et al . Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1):25-33. (EBRT) 10 Kupelian, P et al . Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1):25-33. (RP) 11 Kupelian, P et al . Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1):25-33. (Seeds) 12 Martin, A et al. Permanent Prostate Implant Using High activity Seeds and Inverse Planning with Fast simulated annealing Algorithm: 12 Year Canadian Experience Int J Radiat Oncol Bio Phys 2007; 67(2):334-341. 13 Merrick G, et al . Androgen Deprivation Therapy Dose not Impact Cause Specific Overall Survival after Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2006;65(3):669-677. 14 Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. J Urology 2005;66(5):1048-1053. 15 Phan, T , et al. High Dose Rate Brachytherapy as a Boost for the Treatment of Localized Prostate Cancer. J Urology 2002;177:123-127. 16 Burri, R et al. Young Men Have Equivalent Biochmical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer Int J Radiat Oncol Bio Phys 2010; 77(5): 1315-1321. 17 Potters, L et al. 12 year Outcomes Following Permanent Prostate Brachytherapy in Patients with Clinically Localized Prostate Cancer J Uro l 2005;173:1562-1566. 18 Rossi, C et al . Conformal Proton Beam Radiation Therapy for Prostate Cancer: Concepts & Clinical Results. Comm Oncol 2007;4:235-240. 19 Klein E , et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology 2009;27(1):67-71. (EBRT) 20 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 (Low int) 21 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 (Mid int) 22 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 (High int) 23 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): 433-440. (Seeds) 24 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): 433-440. (Seeds & EBRT) 25 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 Oncol Bio Phys 2008;71(4):1028-1033. 26 Kupelian, P et al . Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1):25-33. (EBRT & Seeds) 27. Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185:495-500. 28 Zelefsky, M et al . Long Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer. J Urology 2006;176:1415-1419. 29 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 Biol Phys 2007;67(2):327-333 30. Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. 31 (Open) 32 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. Moyad, M et al . Statins, Especially Atorvastatin, May Favorably Influence Clinical Presentation and Biochemical Progression-free Survival after Brachytherapy for Clinically Localized Prostate Cancer. Urology 2005;66(6):1150-1154. Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1):16-22. (Seeds & EBRT) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1):16-22. (Seeds & ADT) 36. Galalae, R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer: Is Escalation to Very High Biologically Equivalent Dose Beneficial in All Prognostic Risk Groups? Strahlenther Onkol 2006;182(3):135-141. 37. Taira, A et al . Natural History of Clinically Staged Low and Intermediate risk Prostate Cancer Treated with Monotherapeutic Permanent Interstitial Brachytherapy Int J Radiat Oncol Bio Phys 2010; 76(2):349-354. Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5):1336-42. 38. Demanes, J et al . Excellent Results from HDR Brachytherapy and EBRT for PCA are not Improved by Androgen deprivation Am er J Clin Oncology 2009;32(4):342-347. 39. 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; 76(2):355-360. Dattoli, M et al . Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Radiation and Brachytherapy J Oncology 2010; 2010(Art. Id 471375): 6 pages. Menon, M et al. Biochemical Recurrence Following Robot Assisted RP: Analysis of 1384 patients with a median 5 year Follow-up. Eur Urol 2010; 58:838-846. (Robot) Munro, N et al. ( Leeds) Outcomes for Gleason Score 7, intermediate risk Localized Prostate Cancer Treated with I-125 monotherapy over 10 years. Radiother Oncol 2010;96(1):34-37. Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010; 76(5):1251-1257 (RP) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Proatate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5):1251-1257 (Seeds) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5):1251-1257 (EBRT) Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients treated with I-125 Permanent Prostate Brachytherapy. Int J Rad Onc Biol Phys 2010;76(5):1433-1438. 47.. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Ocntrol Ann Surg Oncol. 2011 18; 2980-87.
Note: The film-based placement technique frequently had the points mid-lumen or mid-rectal wall. This indicates that the actual anterior rectal wall was receiving around 80% of the prescription dose, rather than the 70% that we thought it was getting. Using CT, the anterior rectal wall dose points are closer to the implant. We try to achieve 75% to the anterior rectal wall, but don’t get upset if it is slightly higher, in order for the 100% dose cloud to cover the prostate posteriorly. We don’t get concerned because using the old method which underestimated the rectal wall dose by 10%, our long term data has resulted in ZERO rectal problems.
The differences between Robotic-Assisted Surgery and the traditional open procedure are the way we access the prostate and other anatomy. In the open procedure on the left, we had to make a long incision down the center of the abdomen. In the Robotic-Assisted Procedure on the right, we make several small “key hole” incisions. These access points allow us to insert a high-powered 3-dimensional camera as well as robotic instruments into the abdomen. We can now see, under high-magnification, the prostate and surrounding anatomy. We can then perform a precise & delicate operation with the robotic instruments.
New Developments for Relapsed Prostate Cancer April 1st 2003 Richard Lam M.D. Prostate Oncology Specialists, Marina del Rey, California
Bahn et al Targeted Cryo-Ablation of the Prostate:7 yr Outcomes in Primary Tx of PCa Urology 60 3-11 2002 Boorjian Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J. Urology, 2008;179:1354-1361 3 Critz J, et al. 10-Year Disease Free Survival Rates after Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation and Methodology. J. Urology, 2004;172:2232-2238 4 Galalae R, et al. Long-term Outcome by Risk Factors Using Conformal high Dose Brachy Boost with or without Neoadjuvant androgen Suppression for Localized Prostate Cancer. Int’l J. Oncology Biology Physics, 2004;58(4):1048-1055 5 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology, 2009;27(1):67-7121 6 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology, 2009;27(1):67-71 7 Kupelian P, Kuban D, Thames H, 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’l J. Oncology Biology Physics, 2005;61(2):415-419 8 Kuban D, et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int’l J. Oncology Biology Physics, 2003;57(4):915-928 9 EBRT Kupelian P, et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int’l J. Oncology Biology Physics, 2004;58(1):25-33 10 RP "Kupelian P, et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int’l J. Oncology Biology Physics, 2004;58(1):25-33 11 Seeds Kupelian P, et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int’l J. Oncology Biology Physics, 2004;58(1):25-33" 12 Martin Q. et al Permanent Prostate Implant Using High activity Seeds and Inverse Planning with Fast simulated annealing Algorithm: 12 Year Canadian Experience Int J Radiat Oncol Biol Phys 67: p 334-341, 2007 13 Merrick G, et al. Androgen Deprivation Therapy Dose not Impact Cause Specific Overall Survival after Permanent Prostate Brachytherapy. Int’l J. Oncology Biology Physics, 2006;65(3):669-677 14 Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. J. Urology, 2005;66(5):1048-1053 15 Phan T, et al. 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Long-term Results of Conformal Radiotherapy for Prostate Cancer: Impact of Dose Escalation in Biochemical Tumor Control and Distant Metastases-free Survival Outcomes. Int’l J. Oncology Biology Physics, 2008;71(4):1028-1033 26 27 28 Zelefsky M, Chan H, Hunt M, et al. Long Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer. J. Urology, 2006;176:1415-1419 29 Zelefsky et al Multi Institutional Analysis of Long term Outcome for T1-2 Prostate Cancer Treated with Permanent Seed Implantation with Int J Radiat Oncol Biol Phys 67: p 327-333, 2007 30 31 32 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 Moyad M, et al. Statins, especially Atorvastatin, may Favorable Influence may Favorably Influence Clinical Presentation and Biochemical Progression-free Survival after Brachytherapy for Clinically Localized Prostate Cancer. Urology, 2005;66(6):1150-1154 EBRT and seeds Ho 2009IJORBP 2009 in press Radiation Dose Predicts for Biochemical Control in Int Risk PCa Pts with Low dose rate Brachytherapy p1-7 Seeds ands ADT Ho 2009 JORBP 2009 in Press Radiation dose Predicts for Biochemical control in Int Risk PCa Pts with Low dose rate Brachytherapy p1-7 36. Galalae Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer Strahlentherapie und Onkologie 2006 181 p135-141 37. Taira,Al et al. Natural History of Clinically Staged Low and Intermediate risk PCa Treated with Monotherapy Permanent Interstitial Brachytherapy Int. J. Rad. Onc. Biol Vol 76 p 349-354 38. Demanes, J et al. Excellent Results from HDR Brachytherapy and EBRT for PCA are not Improved by Androgen deprivation Amer J Clin Oncology Vol 32 (4) August 2009 p342-347. 39. Stone et al Local Control Following Permanent Prostate Brachytherapy: Effect of High Biologically Effective Dose on Biopsy Results and Oncologic Outcomes Int. J. Rad. Onc. Biol Vol 76 p 355-360, 2010. Dattoli et al. Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Radiation and Brachytherapy J of Oncology 2010 , J Id 471375, 2010. Menon et al Biochemical Recurrence Following Robot Assisted RP: Analysis of 1384 patients with a median 5 year f/u. 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1. Morris et al BC Cancer Center Presented Seattle Annual Mtg 2006 2. Merrick et al Androgen Deprivation Does not Impact Cause Specific or Overall Survival after PPB Int J Radiat Oncol Biol Phys 65:669-677,2006 (Results -All Hormone naïve Not stated how many received EBRT + seeds) 3, Blasko Grimm Sylvester 2007 4. Hernandez, D Nielsen, Partin,A ( Johns Hopkins) Contemporary Evaluation of the D'Amico Risk Group Classification of Prostate Cancer Urology 70: 931-935 2007 5. Kupelian,P ( Cleveland Clinic) Int J Rad Onc Biol. Vol 58 p 25-33, 2204 6. Potters NY Prostate Institute Monotherapy ofr Stage T1-2 prostate Cancer : radical prostatectomy external beam radiation or permanent seed implantation Radio ad Oncology 71: 29-33 2004 7. Stock, Stone J Urol 169, 2003 8. Sharkey et al Brachytherapy Sharkey et al Brachytherapy vs RP in Pts with Clinically Localized PCa Brachytherapy Current Urology Reports 2002, p1-5 Brachytherapy 2005;4(1):34-44 9. Cohen J, Reviews in Urology Vol 6 Supl 4 p20-26. 2004. 10. Ellis, R et al 4 year Biochemical Outcome after Radio-immunoguided Transperineal Brachytherapy for patients with Prostate Adenocarcinoma Int J Radiat Oncolo Biol Phs 57: p 362-370, 3003 11. Livsey, J et al Hypofractionated Conformal Radiotherapy in Carcinoma of the prostate: Five year outcome analysis Int J Radiat Oncol Biol Phys 57: p 1254-1259, 2003 12. Stokes, Comparison of Biochemical Disease Free Survival of patients ,,, Int J Radiat Oncolo Biol Phys 47 p 129-136, 2000. 13. Thames, H et al Increasing External Beam Dose for t1-2 Prostate Cancer Effect on Risk Groups Int J Radiat Oncol Biol Phys 65: p975-981, 2006 Low intermediate and intermediate Average 72Gy 14. Zelefsky et al High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the outcome of localized prostate Cancer J Urol. 166: 0 876-881, 2001 15. Zelefsky et al Five Year Outcome of Intraoperative Conformal Permanent Interstitial Implantation for Patients with Clinically Localized Prostate Cancer Int J Radiat Oncol Biol Phys 67: p 65-70, 2007. Zelefsky et al Multi-insitutional Analysis of Long term Outcome for T1-2 Prostate Cancer Treated with Permanent Seed Implantation with Int J Radiat Oncol Biol Phys 67: p 327-333, 2007. .Martin Q. et al Permanent Prostate Implant Using High activity Seeds and Inverse Planning with Fast simulated annealing Algorithm: 12 Year Canadian Experience Int J Radiat Oncol Biol Phys 67: p 334-341, 2007 18. Khan et at Expectant management of Localized Prostate Cancer Urology 62: p 793-799, 2003. Intermediate Risk = Mod differentiated Only 21 % PFS at10 years 19. Kuban et al Long Term Multi-institutional Analysis of Stage T1-2 Prostate cancer Treated with Radiotherapy in the PSA ERA Int J Radiat Oncol Biol Phys 57: p915-928, 2003 All pts > 72 Gy 20.Zelefsky, M et at al Improved Biochemical DFS of men younger than 60 yeas with PCa Treated with High Dose Conformal EBRT J Urol. Vol 170 1828-1832,2003 Dose > 80 Gy 21. Zietman et al Comparison of Conventional Dose vs High Dose Conformal Radiation Therapy in Clinically Localized PCa JAMA Vol 294 p 1233-1276. 2005 High Dose EBRT 79 Gy Photons and Protons ( Mixed intermediate with some High Risk) 22. Grimm et al 10 year Biochemical PSA control of PCa with I-125 Brachytherapy Int J Radiat Oncol Biol Phys 51: p31-40, 2001 23. Blasko, Grimm Sylvester et al Pd 103 Brachytherapy for Prostate carcinoma Int J Radiat Oncol Biol Phys 46: 839-850 2000 24.Merrick et al Impact of Supplemental EBRT and/or ADT on Biochemical outcome after Permanent Prostate Brachytherapy Int J Radiat Oncol Biol Phys 61 32-43 Majority 25. Sylvester Grimm Blasko et al 15 year RFS in Clinical Stage T1-3 PCa following combined EBRT and Brachytherapy: Seattle Experience Int J Radiat Oncol Biol Phys 67: p 57-64 26. Symon et ( U Mich) Dose Escalation for Localized PCa: Substantial Benefit Observed with 3D conformal TX Int J Radiat Oncol Biol Phys 57 384-390 2003 27. Bahn et al Targeted Cryoablation of the prostate:7 yr outcomes in primary Tx of Pca Urology 60 3-11 2002 28. Rossi, C et al ( Loma Linda) Conformal Proton Beam RT for PCa Community Oncology 235-240 April 2007 28.Uchida et al Treatment of Localized PCa with High intensity Ultrasound BJU 97 55-61 2006 Uchida et al 5 Year experience with High Intensity Focused Ultrasound using the Sonoblate Device in the treatment of Localized PCa Int J Urol 13, 228-233, 2006 29. Rossi, C et al ( Loma Linda) Conformal Proton Beam RT for PCa ( 79 Gy) Community Oncology 235-240 April 2007 30 Bolla et al Long Term Results with Immediate Androgen Suppression and EBRT in Pts with locally advanced PCa (EORTC study) Lancet 360: 103-108 2002. note low ebrt doses 31. Roupert et al. (France) Outcome after RP in young men with and without a family History of PCa. Urology 67 , 1028-1032. 2006. Very small study of only 36 pts 32. Berglund et al. (CAPSURE) Limited Pelvic LND at time of RP Does not affect 5yr Failure Rates for low intermediate and High Risk PCA Results from Capsure J Urology 177: 526-530, 2007 33. Galalae et al. Long Term Outcome by Risk Factors using HDR Brachytherapy Boost with and without Neoadjuvant androgen suppression for Localized PCA. Int J Radiat Oncol Biol Phys 58. 1048-1055,2004 34. Lee, L. Stock, stone. Role of HT in the management of Int to High risk PCa Treated with Permanent seed implant alone Int J Radiat Oncol Biol Phys 52 444-452 ,2002 35. Lederman et al Retrospective Stratification of a Consecutive cohort of PCa Pts Treated with Combined EBRT and Brachytherapy. Int J Radiat Oncol Biol Phys 49 1297-1303 ,2001 36. Kwok et al ( U Maryland) Risk group Stratification in Pts undergoing permanent I-125 Prostate Brachytherapy as Monotherapy. Int J Radiat Oncol Biol Phys 53 ,588-594 ,2002 37. Potters, L et al 12 year Outcomes Following permanent Prostate Brachytherapy in Patients with clinically Localized Prostate Cancer J Urol 173;1562-1566,2005 38. Zelefsky et al Comparison of 7 Year Outcome Between LDR Brachytherapy and High Dose IMRT with Clinically Localized Prostate Cancer Proceedings of ASTRO Abstract # 1074, 2007 39. Kuban D., Tucker, S,. Et al Long Term Results of the MD Anderson Randomized Dose Escalation Trial for Prostate Cancer IJROBP 2006; 70:67-74,2004 40. Vassil .D et al. (Cleveland Clinic, Kaiser) A comparison of bRFS and Initiation of Salvage Therapy in Pts with Intermediate risk PCa Tx with RP , EBRT or Permanent Seed implantation ASTRO 2007 abstract # 2225 43. Chun et al Anatomic Retropubic prostatectomy Long term recurrence free survival rates for localized PCA. World J Urol 24: 273-280. 2006
Kaplan-Meier analysis of return to 90% baseline HRQOL score over time, with p values comparing return to baseline curves from log rank test. A, urinary function. B, urinary bother. C, sexual function. D, sexual bother. E, bowel function. F, bowel bother.
Smoothed probability plots of the interval likelihood of returning to baseline health-related quality of life as measured by various instruments. A and B) Medical Outcomes Study Short Form-36. C) American Urological Association (AUA) Symptom Index. D–F) University of California–Los Angeles Prostate Cancer Index. RTB = return to baseline; RP = radical prostatectomy; EBRT = external beam radiation therapy.
