Prostate Cancer Comparative Effectiveness · 2020. 12. 11. · Prostate Cancer Comparative...
Transcript of Prostate Cancer Comparative Effectiveness · 2020. 12. 11. · Prostate Cancer Comparative...
Prostate Cancer Comparative EffectivenessJohn Sylvester M.D. 21st Century Oncology
Eliminate Cancer -
- High Total Dose to Prostate Cancer
Avoid Significant Side Effects- Low Dose per Day- Limit Rectal Volume/Dose
Cone Beam-CT
Linear accelerator
Partin TablesStudy of > 5,000 patients that underwent Radical Prostatectomy
Risk of microscopic disease
T Stage (DRE) ECE
Gleason Score SV
PSA Lymph Nodes
TRUS Volume Study
05/00 Seattle Prostate Institute
Transperineal Interstitial Permanent Prostate Brachytherapy(seed implant)
Quality & Experience is Critical
Day 1 post-implant dosimetry
Prostate
Full DoseRadiationInside and outside of prostate
Seeds Inside and outside of prostate
Post Operative
Discharge to home 1 hour later with: • Alpha-blockers, NSAIDs, Antibiotics• Ice bag on perineum 20minutes on/off repeat all day• Light lunch, normal dinner • Post-op dosimetry CT the next day.• Return to work in ~3-4 days• Avoid strenuous activities and sex for ~ 2 weeks• Avoid upright bike seat 2 months
Cone Beam-CT Image Guided-IMRT (BEAM)
Cone Beam-CT
Linear accelerator
Multiple fields (>100-200)
Doses
4 field: 68 Gy
3dCrt: 74 Gy
IMRT: 78 Gy
IGRT: 81 Gy
• Normal structures significantly spared (e.g. rectum V70 19% vs 1.7%)
• Side effects Graded 1 (very mild)-5 (severe)
• Acute grade 2 toxicity (mild) : Rectal 80% vs 13% p=0.004. Bladder 60% vs. 13%, p=0.014.
• No grade 3-5 toxicity
• Conclusion: IMRT with daily image (IGRT) results in lower dose to normal structures which means less side effects
Prostate Cancer IMRT +/- IGRT Chan LW et al IJROBP ;69,No 3 2007,abstr.#2242
Rectal Balloon
Rectal Balloon1) Lower rectal dose2) Less movement3) Normal diet4) Lower small bowel dose
CBCTIGIMRT
Cone-beam CTImage GuidedIntensity Modulated Radiation Therapy
SpaceOARFDA approved 2:1 randomized trial
SpaceOAR
Low Intermediate High
PSA < 10 PSA 10.1-20.0 ng/ml PSA > 20 ng/ml Gleason < 7 and/or Gleason = 7 Gleason 8-10 T1c-T2a and/or Stage T2b Stage > T2c,T3
RISK Groups
Don’t Use MSKCC Nomogram to compare results!!!
5-YR Relapse-free Survival Low risk usually seeds
alone
Intermed. ebrt
+ seeds
High risk ebrt+seeds +/-
hormones
Seeds MSKCC (IJROBP 2009) 97% 89% ------------
Seeds Cleveland Clinic (IJROBP ;2008) ------------- 89% -----------
Seeds Sylvester Seattle (IJROBP 1;2007) -------------- 80% (15-yr) 68% (15-yr)
Seeds Sylvester Seattle (Brachy 5;2009) --------------- 92% (9-YR) --------
Seeds Frank..Sylvester (Cancer Epub 2011) 99.1% (7-yr) ----------------- ------------
Seeds Multi-institutional study IJROBP Feb 2009 --------------- 86%
HDR Demanes- (UCLA JCO 2009 ) (10-yr) 92% 87% 63%
RP Mayo Clinic RP (J. Urol April 2008) 82% 10-yr 65% (10yr) 55% (10yr)
RP JHU RP (Hernandez J Urol 2007) 94% 76% 54%
RP Cleveland Clinic RP (IJROBP 69,3,2007) 86% (10yr) 79% (5yr)
EBRT Protons- IJROBP 78,3 s146 ASTRO 2010 (10-yr) 92% 69% -----------
IMRT MSKCC (81Gy) J Urol; 176, Oct 2006 89% (8yr) 78% (8yr) 67% (8yr)
Immune Baylor Prostatak + 76Gy IMRT 2006 100% (~6yr) 95% (~6yr) 80% (~6yr)
HiFU HiFU European Urology 65 (2014) 76% (8yr) 63% (8yr) 57% (8yr)
Cryo Dhar et al BJU int, 2011 Jul 1 (Epub) 79.4% 61.4% 58%
HIFU Dickinson et al; Mar 2016 Urology
• 569 patients 8 hospitals academic registry
• 29% required re-treatment
• 5-yr relapse free survival
• Low risk = 87%
• Intermediate= 63%
• High risk = 58%
• Impotency = 71%
• Incontinence = 12%
Comparative Analysis of Prostate Specific Antigen Free Survival Outcomes for Patients with Low, Intermediate and High Risk Prostate Cancer Treated By Radical Therapy.
Results of the Prostate Cancer Results Study Group. Grimm, Sylvester et al IJROBP 2009. Updated BJU Int 2012;109(sup1):22-29
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7
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Seeds
Surgery
EBRT
5
22
← Years from Treatment →
CRYO
• Prostate Cancer Results Study Group • Numbers within symbols refer to references
1
12 24
14 8
2
23
HIFU
% P
SA P
rogr
essi
on
Fre
e
11
15
Protons
21
4
18
9
10
EBRT & Seeds
25
Robot RP
26
27
HDR
2829
30
313233
34
1936
37
38
LOW RISK RESULTS
3 39
35
40
42
43
13EBRT
Brachy
Surgery
Trea
tmen
t Su
cces
s
John Sylvester MD21st Century Oncology
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40
50
60
70
80
90
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Brachy
Surgery
EBRT
CRYO
HIFU
29
22
21
519
% P
SA P
rogr
essi
on
Fre
e
18
12
28
317
10
32
9
8 2
25
1
13
Protons
HDR
← Years from Treatment →
• Prostate Cancer Results Study Group • Numbers within symbols refer to references
15
436
37
38
+
Seeds Alone
Seeds + ADT40
Robot RP
41
42
44
43
45
46
INTERMEDIATE RISK RESULTS
7
11
14
20
35
34
39
2324
16
6
26
33
EBRT & Seeds
EBRT Surgery
Brachy
EBRT & Seeds
Hypo EBRT
EBRT, Seeds + ADT
Trea
tme
nt
Succ
ess
John Sylvester MD21st Century Oncology
Comparative Analysis of Prostate Specific Antigen Free Survival Outcomes for Patients with Low, Intermediate and High Risk Prostate Cancer Treated By Radical Therapy.
Results of the Prostate Cancer Results Study Group. Grimm, Sylvester et al IJROBP 2009 Updated BJU Int 2012;109(sup1):22-29
12/11/2020
611
36
25
15
5
EBRT Seeds +ADT
19
30
16 20
18
29% P
SA P
rogr
essi
on
Fre
e
17
21
8
9
22
24
26
37
41
12
Protons
HDR
← Years from Treatment →
• Prostate Cancer Results Study Group • Numbers within symbols refer to references
42
4344
45
46
47
Robot RP
48
49
101
102
103
104
105
106
107
109
HIGH RISK RESULTS
10
23
35
108 4
2
31
39
32
33
34
38
EBRT, Seeds & ADT
Brachy
EBRT Surgery
EBRT & ADT
EBRT & Seeds
Hypo EBRT
Trea
tmen
t Su
cces
s
1
7
John Sylvester MD21st Century Oncology
Comparative Analysis of Prostate Specific Antigen Free Survival Outcomes for Patients with Low, Intermediate and High Risk Prostate Cancer Treated By Radical Therapy.
Results of the Prostate Cancer Results Study Group. Grimm, Sylvester et al IJROBP 2009 Updated BJU Int 2012;109(sup1):22-29
HiFU
ASCENDE-RT RCT Trial
For the Brachytherapy Blast Issue this month, Dr. Mira Keyes has graciously written a summary of the ASCENDE-RT RCT trial, PI Dr. James Morris, that was presented both at the ASCO GU Symposium this year, as well as the
April ABS meeting in Orlando. This RCT is a "game changer" in the management of intermediate- and high-risk prostate patients. All GU
oncologists should be very familiar with the study design and results. In this study of nearly 400 men, both groups received 12 months of ADT and pelvic RT to 46 Gy. They were than randomized to either an EBRT boost of 32 Gy (total EBRT dose of 78 Gy) or an LDR-PB boost of 110 Gy. At over 6
years of follow-up the PSA PFS curves dramatically diverge with a 50% reduction in the failure rates for those who received a LDR-PB boost. The
absolute difference at 9 years for the intermediate-risk LDR-PB group was 24%, and for the high-risk group 20% (P = 0.001 - 0.05). The prevalence of
GU 3 toxicities were 8.6% vs 2.2% for LDR vs EBRT - primarily urethral strictures in which 50% resolved with dilatation. These results are
staggering and practice changing. We thank the vision and leadership of Dr. Morris and the British Columbia Cancer Agency for conducting this sentinel work. At the ABS, we predict this RCT, as well as the results of other critical
studies, will solidify the importance of dose escalation with BT.
Daniel Petereit, MD, FASTRODavid K. Gaffney, MD, PhD, FASTRO, FACR
ASCENDE-RT RCT Trial
Radical prostatectomy, external beam radiotherapy, or EBRT with Brachytherapy boost and disease progression and mortality in patients with Gleason score 9-10 cancer
Kishan et al JAMA march 6, 2018 .vol 319, N9
• 1,809 patients at 12 teriary medical centers
• 5-year Prostate cancer specific mortality: 3% Brachy boost, 13% EBRT, 12% Surgery
• 5-Year metastatic disease: 8% Brachy boost, 24% Surgery, 24% EBRT
• 7.5-year overall mortality: 10% Brachy boost, 18% EBRT, 17% surgery
• Only 41% of EBRT patients received greater than 70Gy and 2 years ADT
Acute Temporary Side Effects – IMRT (Beam)
• Obstructive Urinary Symptoms ~ few weeks s/p tx--- Usually mild
• Retention (Catheter) --- much less than 1% of patients
• Increase BM frequency --- common
• Diarrhea --- Mainly if lymph nodes treated
• Fatigue --- usually mild
Brachytherapy (Seeds)
• Obstructive urinary symptoms –moderate
• Catheter 6-35% of patients (~2-4 weeks)
• Alpha blockers usually for 3- 6+ months
• Pain with Urination ~ 24-72 hours
• Time off work ~ 1-2 days
• Diarrhea – very rare
• Fatigue – usually mild if any
• O.R. Procedure and anesthesia
Possible Late / Long Term Side Effects
- Rectal: bleeding ~ 1 yr s/p treatment.- More frequent BM’s, looser stools, more
sensitivity to roughage in diet- Impotency: age and current function dependent- Reduced volume ejaculate- Bladder: Permanent frequency urgency- Radiation induced malignancies (rare)- Dysuria (burning sensation during urination)- Stricture (restricted flow)- Incontinence - rare
Later Possible Side EffectsIMRT (81Gy) (Beam)MSKCC (Zelefsky et al J Urol 2010 Dec)
SeedsMSKCC(Zelefsky et al J Urol 2010 Dec)
Protons(EuropeanUrology 60 (2011)Pp 908-916)
Number Patients 281 448
Grade 2 rectal 1.4% 5.1% Highesttoxicity
Grade 3 Rectal 0% 1.1% Highesttoxicity
Grade 4 rectal 0% 0%
Grade 2 GU 4.3% (Stricture- tx Flomax)
15.6%
Grade 3 GU 1.4%(Stricture- tx Dilation)
2.2%
Proton Beam therapy has higher gastrointestinal
Toxicity any other radiation option
John Sylvester M.D. 21st Century Oncology-Lakewood Ranch Oncology Center
Late Gastrointestinal Toxicities Following Radiation Therapy for Prostate CancerKim et al European Urology 60 (2011) 908-816
John Sylvester M.D. 21st Century Oncology-Lakewood Ranch Oncology Center
0
20
40
60
80
100
Urinary Function Bowel Function Sexual Function
Prostatectomy
Brachytherapy
EBRT
Controls
Surgery
Seeds +/- EBRT
Old form of EBRT
controls
HRQOL: UCLA-PCIProstatectomy vs brachytherapy vs EBRT (not IMRT)Measured QOL 2.5 years post treatmentHigher the bar = better the function
* = poor functioning
Davis JW, et al. J Urol. 2001;166:947-952.
**
*
*-Statistical Significance
(Surgery & Seed patients are younger than ebrt pts)
Used 3dCrt , (Modern IMRT has less side effects)
SexualBowelUrinary
At 5 Years, Brachytherapy Shows Quality-of-life Advantages over Radical Prostatectomy for Favorable-risk Prostate Cancer Crook et al JCO;September 1, 2011, Volume 2, Issue 13
P < 0.05 = significant
*
*
*
*
*
*
*
*
New Radiation Therapy Innovations
• Stranded Seeds: - prevents seed migration
• Cs-131 Seed shorter 1/2life- maybe shorter duration side effect?
• Rectal Balloon - reduces rectal side effects and prostate
motion
· CT/MRI Fusion planning
– reduces side effects
John Sylvester M.D. 21st Century Oncology-Lakewood Ranch Oncology Center