RT for High-Risk and Post-operative Prostate CancerASTRO Refresher Course 2013

Stanley Liauw MDAssociate Professor

University of ChicagoDept of Radiation and Cellular Oncology

Objectives• Review evidence regarding the role of RT for

high-risk (locally advanced) prostate cancer• Review evidence regarding the role of RT after

radical prostatectomy• Review treatment factors which influence

outcomes (disease control, toxicity) • Review technical aspects of post-operative

radiation planning and treatment

Pre-test question1. There are now 3 randomized studies testing adjuvant RT vs. observation for men with pT3 prostate cancer or positive margins after radical prostatectomy, each with >9 years of follow-up. Which of the following studies demonstrate a survival benefit?

A. EORTC 22911 (Bolla)B. SWOG 8794 (Thompson)C. ARO 9602 (Wiegel)D. RTOG 9601 (Shipley)

Pre-test question2. A 71 year old man with minimal comorbidity who presents with clinical T3, intact adenocarcinoma of the prostate, Gleason score 4+4, and PSA 22 should be treated with RT/ADT rather than ADT alone because: A. Biochemical failure at 10 years is ~75% with ADT alone, and only ~50% with RT/ADTB. Cause specific survival at 10 years is reduced by half (~24% with ADT alone, and ~12% with RT/ADT)C. Overall survival at 10 years is improved by ~5% (~65% with ADT alone, and ~70% with RT/ADT)D. All answers are incorrect; ADT alone is preferred because this man is >70 years old

High-Risk, Intact Prostate Cancer

Definitions: NCCN risk category

• Life expectancy estimation less critical than with low or intermediate risk

Recurrence risk Features ? surveillance, if life expectancy:

Very low T1c, Gleason score ≤6, PSA < 10, fewer than 3 cores positive, ≤50% involved in each core, PSA density <0.15 ng/mL/g

<20 years

Low T1-2a, Gleason score ≤6, PSA < 10 <10 years

Intermediate T2b-c OR Gleason score 7 OR PSA 10-20 <10 years

High T3a OR Gleason score ≥8 OR PSA >20 Not specified

Very high (locally advanced)

T3b-4 Not specified

Metastatic Any nodal or distant metastasis

Definitions: AJCC (2010)

• Stage has been replaced by prognostic group • NCCN High risk corresponds to Groups IIB – IV

General management options

• EBRT with long term ADT• EBRT with brachytherapy +/- long term ADT• Radical prostatectomy (if no fixation) and LND +/- RT• ADT alone = only for men not candidates for local therapy

RT/ADT vs. ADT

SPCG-7Widmark Lancet Onc 2009

NCIC/MRCWarde Lancet 2011

Eligibility T3 or T1b-2b/WHO G2-3; PSA<70; pN0 if PSA > 11

T3-4, or T2 with PSA>40, or GS8 with PSA>20; cN0

Patients n=87578% T3

Median PSA 1619% WHO G3

n=120583% T3

Median PSA 2818% GS 8-10

Treatment 70 Gy (no pelvic RT) 65-69 Gy (45 Gy pelvis)

Indefinite ADT Anti-androgen(3 mo LHRH)

LHRH agonist(2+ wk anti-androgen)

Median fu 7.6 y 6.0 y

• 2 large randomized trials test RT/ADT vs. ADT

Role of RT/ADT

• Local therapy improves survival in men with high risk disease treated with ADT

• Grade 3 toxicity limited with RT (≤2%); mild/moderate symptoms more common but QOL shows acceptability– Risk benefit ratio greater with IMRT/IGRT?

SPCG-7

• 10-yr BF 26/75; OS 70/61 • All subsets favorably affected

24%

12%

Cause specific mortalityNCIC/MRC

• 7-yr PCSM 9/19

Overall survival74%

66%

Primary ADT for localized cancer

• Trials may alter practice patterns (hopefully)

Cooperberg, JCO 2010Low risk Int risk High risk

Role of RT/ADT• Several randomized trials test RT/ADT vs. RT

n Eligibility ADT Important endpoints affectedEORTC(1997,2010)

412 T3-4, WHOG3

36 m vs. 0 m bRFS, LC, DM, CSS, OS

RTOG 8531(1997,2005)

997 T3, or N+ (non-bulky)

Indef. vs. none bRFS, LC, DM, CSS [OS for GS7-10]

RTOG 8610(1995,2001)

456 T2-4 bulky, orN+

4 m vs. 0 m bRFS, [LC, DM, CSS, OS for GS2-6]

TROG 9601(2005,2011)

818 T2b-4; N0 0 vs. 3 vs. 6 m bRFS, LC [DM, CSS, OS for 6 m]

Harvard(2004,2010)

206 PSA 10-40, or GS7+, T1b-2b

6 m vs. 0 m FFbF, FF salvage, CSS, OS

RTOG 9408(2011)

1979 T1b-2b, PSA≤20; cN0

4 m vs. 0 m FFbF, DM, CSS [OS for int-risk]+biopsy at 2 y

RT is conventional fractionation, 66-70 Gy; whole pelvic RT for high risk patients

The addition of ADT (dual agent) to RT improves survival

Role of RT/ADT• Other randomized trials test length of ADT

n Eligibility ADT Important endpoints affectedRTOG 9202(2003,2008)

1554 T2c-4, N0; PSA<150

28 m vs. 4 m bRFS, LC, DM, CSS [OS for GS8-10]

EORTC(2009)

970 T2c-4, or N+PSA<160

36 m vs. 6 m CSS, OS

Canada(abs 2013)

630 T3 or PSA>20or GS8, N0

36 m vs. 18 m None

Using conventional RT to treat locally advanced disease, there is a survival advantage with

longer term ADT

RT is conventional fractionation, 66-70 Gy; whole pelvic RT for high risk patients

Hormonal therapy• Affects local control and distant control

– Distinct from surgical studies with ADT

• Long term ADT is better for highest risk– ? Improved control of micrometastases– ? LC more problematic in high risk patients

• Unknown how higher doses of RT should influence the use of concurrent ADT– Retrospective analyses offer some hints until

prospective studies are completed

• There are potential negative effects of therapy

Hormonal therapy

– In 8 RCTs, ADT improved PCSS and OS without resulting in excess cardiovascular deaths

– Sending patients for “ADT clearance” is not necessary (Levine, Ca J Clin 2011)

Nguyen JAMA 2011

• Does ADT ↑risk of cardiovascular mortality?

RT dose• Supported by several randomized trials

to improve biochemical control

Kuban, IJROBP 2008

78 Gy73% at 10 y

70 Gy50% at 10 y

RT dosen Eligibility RT dose (Gy)* FFBF at 5 y

MDACC(2002,2008)

301 T1b-3 78 vs. 70 73/50 (10 y); trend FFDM and CSS

Harvard/LLMC(2005,2010)

393 T1b-2b, PSA<15

79.2 vs. 70.2 83/68 (10 y)

Dutch(2006,2008)

669 T1b+, GS6+, PSA<60

78 vs. 68* 64/54

MRC(2007)

843 T1b-3a, PSA<50

74 vs. 64* 71/60

GETUG(2011)

306 T1b-3, PSA<50 80 vs. 70 72/61

*ADT allowed

• Dose escalation is supported for all risk categories• It is likely that local control remains a problem even

with dose escalation

Brachytherapy boost • Retrospective data suggest favorable PSA

control rates for high-risk diseasen High risk pts EBRT ADT Implant FFBF

Mt. Sinai IJROBP, 2004

132 Med PSA 10-20, 28% with GS 8+

14% with T3

45 GyPSV only(100%)

9 mo(100%)

Pd 86% at 5 yr

Wheeling WV BJUI, 2011

284 Median PSA 10Median GS 8+34% with T2c+

45 Gy, Low pelvis

(91%)

~12 mo(63%)

I or Pd 89% at 12 yr94% CSS at 12 yr

SydneyBJUI, 2012

90 Median PSA 1525% with GS 8+

25% T3

45 Gy, low pelvis

(100%)

12 mo(100%)

HDR 80% at 5 yr54% at 10 yr

MSKCCBrachy 2013

73 85% with GS8+No T3

50.4 Gy, PSV only(100%)

~9 mo I, Pd or HDR

80% at 5 yr

Note contribution of patient selection and high quality implant centers

Combination EBRT/brachytherapy• 848 outcomes studies (n=14,793 high risk pts)

Grimm, BJUI 2012

• Suggestion of improved outcomes with EBRT + brachytherapy in comparison to EBRT monotherapy

EBRT vs. EBRT/brachytherapy

• ↑FFBF and CSS with combined modality RTShilkrut, Cancer 2013

Una

djus

ted

Kapl

an M

eier

Adju

sted

Cum

ulat

ive

inci

denc

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40%

13%

Cause specific mortalityBiochemical failure

14%7%

HR 0.35 with CMRTHR 0.45 with CMRT

Retrospective comparison of EBRT (~78 Gy, n=510) and CMRT (n=448)

Role of ADT with escalated dose• In retrospective series, ADT use is usually still

associated with improved FFBF and CSS – Effect may be reduced with highest doses of RT

020406080

100

Localfailure

Distantfailure

No ADTADT

020406080

100

Localfailure

Distantfailure

No ADTADT

High

Med

Low

High

Med

Low

Conventional RT Dose escalated RT

Hypothetical model of risk of relapse: ADT use/longer duration may be less important when local control is improved, especially if local failure is the primary problem

Role of ADT with escalated dose• Magnitude of benefit may depend on dose and T-stage

• PSA response might also be helpful (D’Amico Lancet Onc 2012)

– PCSM at 8-years is 5% if PSA nadir ≤0.5 (vs. 27%)

– Study of 3,666 men treated with EBRT and varying ADT length– Impact of ADT on BF is non-linear (first 6 mo >> after 18 months)

Williams IJROBP 2011

>68 Gy ≤T2

≤68 Gy T3

RT volume• Pelvic nodes can be involved in high risk disease

Shih IJROBP 2005

Lymph node involvement goes beyond ‘standard’ US template >50% of time

Nanoparticle data indicate common involvement and size < 1 cm

Pubic bone

Weckermann J Urol 2006

1055 men undergoing LN evaluation:

RT volume

n Eligibility Arms Important endpoints affectedRTOG 9413(2003,2007)

1292 T2c-4 GS6+, or LN+ risk >15%;PSA<100

WP vs. PONHT vs. AHT

Trend PFS for WPRT/NHT (and PORT/AHT)

GETUG-01(2007)

444 T1b-3 Low pelvis RT vs. PORT(ADT allowed)

None

• Does pelvic radiation improve outcomes?

Lawton IJROBP 2007

WP/NHT vs. PO/NHT p=0.066WP/AHT p=0.022PO/AHT p=0.75

RT volume

5-year rates late toxicity

WPRT(n=309)

Mini-pelvis(n=170)

Prostate(n=131)

P value

Grade 2GIGU

15%15%

9%15%

7%6%

0.0020.03

Grade 3GIGU

4%3%

1%2%

0%0%

0.0060.24

• Does pelvic radiation add toxicity?

• The risk benefit ratio for 2D pelvic RT is unfavorable• Today, careful patient selection and technology may

influence the decision to include pelvic lymph nodes– Note: Classic ADT trials did include pelvic lymph nodes

Roach IJROBP 2006

Summary: High risk, intact prostate cancer• Role of RT+ADT established by RCTs

– Long term ADT superior to short term ADT• Dose escalation likely provides further benefit

– Brachytherapy boost may be an attractive alternative in select cases

• Pelvic nodal RT (2D) thus far demonstrates an unfavorable risk-benefit ratio

• The “standard of care” may change with incorporation of newer technology (IMRT, IGRT), and new drugs– Trials have been designed to address these issues

Post-operative Prostate Cancer

Outcomes after prostatectomyOverview Risk factors %bNED-10 y

8 centersKarakiewiczUrol 2005N=5831

1983-2000Med fu 25 mo

bNED 61% at 10 y0% adj RT

+ marginsECE, +/- marginsSVI, +/- marginsLNI, +/- margins

3625/4612/2014/8

Wash U RoehlJ Urol 2004n=3478

1983-2003Med fu 65 mo

bNED 68% at 10 y6% adj RT

Stage cT3Gleason score ≥8ECE, +/- margins

SVILN

1532

53/622612

BaylorHullJ Urol 2002n=1000

1983-1998Med fu 47 mo

bNED 75% at 10 y0% adj treatment

+marginsECE alone

SVILN

3671377

U ChicagoOrvietoBJU 2006n=996

1994-2004Mean fu 76 mo

bNED 86% at 10 y0% adj treatment

+/- marginsSVI

60/90~50

(≤50% highlighted)

Randomized trials: adj RT vs obs

EORTC 22911Bolla Lancet 2012

SWOG 8794Thompson J Urol 2009

ARO 9602Wiegel JCO 2009/ GU ASCO 13

Eligibility pT2-3N0ece, svi, or psm

pT2-3N0ece, svi, or psm

pT3N0ece, svi, psm

Patients n=10051992-2001

Age 65 yMed preop PSA 12

Postop PSA ≤0.2 in 90%

n=4251988-1997

Age 65 yMed preop PSA ~10

Postop PSA <0.2 in 66%

n=3071997-2004

Age 65 yMedian preop PSA ~9

Postop PSA ≤0.2 in 100%

RT techniques 60 GyConventionalProstate bedWithin 4 mo

60-64 GyConventionalProstate bedWithin 4 mo

60 Gy3D conformalProstate bedWithin 3 mo

Median fu 10.6 y 11.5 y 9.3 y

EORTC 22911 SWOG 8794 ARO 9602

bNED

Endpoints(primary)

bPFS, LRF-10 y (7/17)DM (~11), OS-10 y (~78)bPFS: all except age>70cPFS: age<65, +marginsOS: none (worse if >70)

Clinical PFS-10 y (~70/50)On ADT- 5y (10/21)MetFS-15 y (46/38)

OS-15 y (47/37)

bPFS

bPFS: +margins, PSA>10, pT3a

RT toxicityAcuteLate

~20% Gr2; ≤5% Gr3~10% Gr2; ≤2% Gr3

Any grade 24% (vs 12%)proctitis, stricture,

incontinence

12% Gr2; 3% Gr3~ 5% Gr 2; 1% Gr3

Randomized trials: adj RT vs obs

61% at 10 y

41% at 10 y

~50% at 10 y

~25% at 10 y

56% at 10 y

35% at 10 y

Role of adjuvant RT• Adjuvant RT for all pT3 and +margins?

Salvage RT is also effective for a rising PSA post-operatively

YES (adjuvant) No (early salvage)• Supported by Level I evidence • Risk of significant morbidity is

low• Might allow for: lower RT

doses, smaller volumes, less need for ADT with RT, with similar or better result than salvage therapy (?)

• RCTs did not test adjuvant vs. early salvage

• Early salvage ≈ adjuvant RT (?)• Perhaps not all benefit

equally from adjuvant RT• Avoid overtreatment, reduce

risks and costs

Salvage RT• Retrospective data support salvage RT

n Patients Treatment Important endpoints affectedStephensonJCO 2007

1540 RT in all menMedian PSA 1.1

51% margin+22% GS 8+; 3% N1

Median 64.8 Gy14% ADT

FFBF-6 y 32%

TrockJAMA 2008

635 Observation or RTMedian PSA ~0.8

43% margin +28% GS 8+; 20% N1

Median 66.5 Gy12% ADT

RT improves CSSAt 10 years, ~85% vs. 62%

CotterCancer 2011

519 Observation or RT59% margin +

29 GS 8+; No N1

Median 66 Gy16% ADT

RT improves OS

Salvage RT is associated with better CSS and OS in select series

Salvage RT

PSA ≤ 0.5PSA > 1.5

48%18%

FFP-6 y FFP associated with: • Gleason score• Pre-RT PSA• LN involvement• Margin status• PSA DT• Use of ADT

Stephenson, JCO 2007

– Similar to intact prostate (T/N, Gleason, PSA) + two post-op factors (margins and PSA DT)

Salvage RT• Meta-analysis of 41 salvage RT studies

King IJROBP 2012

– Best outcomes with lower pre-RT PSA (0.2 probably better than 0.5)

2.6% loss of RFS per ↑0.1 ng/mL PSA

“Early” salvage RT• Matched paired analysis of adjuvant and observation

with early salvage (PSA ≤ 0.5) as needed (n=890)– RT 65 Gy to the prostate bed only, no ADT

– Early salvage RT ≈ adjuvant RT; avoids overtreatment– Trials are accruing to address this issue

5-year FFBF 78% vs. 82%

Briganti Eur Urol 2012Median FU 47 mo

New referral with a post-op PSA• “Post-op active surveillance” analogy

– Weighing natural history of disease vs. life expectancy

Freedland JAMA 2005

15-y CSS 94%: BF > 3 y after RP, PSA DT ≥ 15 mo,GS < 8

Salvage RT: patient selection• Clinical factors are used to prognosticate outcome

6-year progression-free probability after salvage radiotherapy

Stephenson JCO 2007

• Output typically 30-70%• Largest impact for PSA DT,

pre-RT, GS, LN status, ADT

Salvage RT: patient selection• Nomogram caveats

– The nomogram is merely a model based on heterogeneous data using a BF endpoint

– What if the nomogram predicts a poor outcome?• Men without biochemical control can s�ll have ↓DM

(Swanson, JCO 2007) and ↑CSS• Men with a fast PSA doubling �me can have ↑CSS (Trock,

JAMA 2008)

• Selection by clinical factors may not need to be as refined as once thought

• Patient selection would ideally be better defined with factors other than clinical disease parameters

Salvage RT: imagingRecommended? Comment

Ultrasound and biopsy

No Moderate sensitivity only; only evaluates prostate bed

CT abdomen/pelvis No Low sensitivity with low PSA

Bone scan If PSA >10, PSADT<6 mo, velocity >0.5 ng/mL/mo; or sx

Low sensitivity with low PSA; indeterminate findings possible

RIS (e.g. Prostascint) Not routinely Accuracy questionable; does not predict better salvage RT response

PET (C11, F18) Not routinely Accuracy low for PSA <2

MRI (Endorectal,DCE, DWI)

Consider, especially for pT3 and positive margins

Most favorable sensitivity and specificity (Lymphotropicnanoparticles not approved)

Adapted from: Beresford, Clin Onc 2010

Salvage RT: Endorectal MRI

• 88 men evaluated for salvage RT, median PSA 0.3– Radiographic abnormalities in prostate bed in 24%– Likelihood correlated with preRT PSA– Abnormalities seen on T2 MRI (90%) > DWI or DCE

• Unclear whether MRI findings should influence patient selection or treatment

Liauw IJROBP 2013

“Local recurrences” as seen on endorectal MRI:

Optimizing salvage RT • Data driven approach towards ‘intensification’

of therapy to improve outcomes– Quality of data is weaker compared to intact

prostate cancer

Available dataRT dose Retrospective

RT volume RetrospectiveCombined ADT Limited prospective, and

Retrospective

RT dose• Can dose escalation be extrapolated from the

intact setting?– Despite less certainty with target location, there

exists a dose response

King IJROBP 2012 Ohri IJROBP 2011

Higher RT doses may compensate for a higher pre-RT PSAPSA 1, 70 Gy = PSA 0.6, 65 Gy

70 Gy

65 Gy

RT dose• Select retrospective series and dose escalation

n RT dose FFBF CommentsKing(IJROBP 2008)

8438

70 Gy60 Gy

58% at 5 y25% at 5 y

Higher dose improves FFBF

Siegmann(Str Onk 2011)

67234

70.2 Gy66.6 Gy

88% at 2 y71% at 2 y

Higher dose improves FFBF(but patients selected by PSA decline >20%)

Bernard(IJROBP 2010)

86124154

>66.6 Gy64.8-66.6 <64.8 Gy

57% at 5 y46% at 5 y39% at 5 y

Higher dose improves FFBF

Ost(Eur Urol 2011)

136 76 Gy(all IMRT)

56% at 5y IMRT to 76 Gy is safeGr2+ toxicity 8% GI, and 22% GU at 5 yr

Goenka(Eur Urol 2011,IJROBP 2012)

20580

≥70 Gy<70 Gy

(Mix of IMRT and 3D RT)

~37% at 7 y Higher dose did not improve FFBFIMRT to ≥70 Gy reduces late GI toxicity Gr2+ toxicity 2% GI, 17% GU (IMRT) at 5 yrGr2+ toxicity 10% GI, 17% GU (3D) at 5 yr

– Higher dose is associated with better biochemical control in several series; IMRT may reduce late toxicity

RT volume• Does inclusion of pelvic lymph nodes improve

efficacy of salvage RT?– With a median PSA 0.5, 23% of men had +LNs on

nanoparticle MRI (Ross, Clin Imaging 2009)

Moghanaki Cancer 2013

Shih IJROBP 2005

Pros

tate

bed

Who

le p

elvi

s

RT volume• Retrospective series and nodal radiation

n Volume FFBF CommentsKim (Cl Pr Ca 2004)

2125

Pelvic LNBed only

~50% at 10 y WPRT does not improve FFBF

Spiotto(IJROBP 2007)

7242

Pelvic LNBed only

47% at 5 y21% at 5 y

Benefit of WPRT only in select group (pT3, GS 8-10, preop PSA >20 with ADT)

Moghanaki(Cancer 2013)

112135

Pelvic LNBed only

82% at 5 y69% at 5 y

Benefit of WPRT only in select group (pre RT PSA ≥0.4; HR 0.47 for bNED)

Alongi(RadOnc 2009)

9181

IMRT to WP3D to WP

-- IMRT reduces acute GI toxicityAcute Gr2+ toxicity 7% uGI, 3% LGI (IMRT)Acute Gr2+ toxicity 22% uGI, 9% LGI (3D)

– Pelvic RT is associated with better biochemical control in select men; IMRT may reduce acute toxicity

– Await results from RTOG 0534

Use of ADT

n Eligibility RT ADT Important endpointsRTOG 9601(ASTRO 2010)

771 pT2-3N0 with PSA 0.2-4.0

64.8 Gy 2 years (bicalutamide)

vs. none

ADT with salvage RT ↓DMFFBF-7 y (57/40), DM-7 y (7/13)

RTOG 8531(2005)

173 N1 subsetincludes postop

60-70 Gy

Indef (LHRH) vs. none

ADT with salvage RT ↑OSFFBF-5 y (54/33), DM, CSS, OS

• Prospective, randomized studies

– 9601: ADT (150 mg bicalutamide x 2 y) ↓DM– Other studies are accruing to evaluate ADT:

Study Accrual goal Eligibility ArmsMRC PR10 N=4000

2007-PSA <0.4 Adj vs early salvage RT with

0 vs 4 vs 24 mo ADT

RTOG 0534 N=17642008-

PSA 0.1-2.0; T2-3N0, GS≤9

PBRT vs. PBRT/ADT vs. WPRT/ADT (ADT for 4-6 mo)

Use of ADT

• Excellent FFBF with long term ADT in comparison to other published studies without ADT

• Retrospective data are generally supportive for ADT with salvage RT for ↑FFBF but results are mixed

• ADT impact may be influenced by dose and volume considerations

n Eligibility RT ADT Important endpointsSunnybrook(2009)

78 pT3 or R1 60-70 Gy

2 years (adj CAB/LHRH)

Adjuvant: FFBF-5 y 100%Salvage: FFBF 5-y 85%

Sunnybrook(2009)

75 pT3 or R1, PSA detectable

60-66 Gy

2 years (adj CAB/LHRH)

Salvage: FFBF 5-y 92%, 7-y 79%

SWOG S9921(2011)

481 PSA >15, pT3b, N1, GS8-10, R1

Only in 27%

2 years (CAB) FFBF-5 y 93%

• Prospective, single arm studies

Late Toxicity (Grade)

• Comparable toxicity rates to intact setting• IMRT/3D treatment likely better than 2D

treatment and may facilitate dose escalation• Treatment factors including volume and dose

likely have impact

RT Modality (+/- ADT as indicated)

GI Toxicity GU Toxicity References

Gr2 Gr3 Gr2 Gr3

Adjuvant RT 5 2 5 2 EORTC

Salvage RTStandard dose76 Gy with IMRT

58

11

1022

13

Multi-institutionalBelgium

Toxicity (Symptom Scores)

– Post-op IMRT does not clearly worsen continence

Corbin, PRO in press

• Do we need to wait for continence recovery?– Patient reported QOL surveys can still show

improvement in continence after RT

NCCN Post-op Guidelines

• “Standard of care” allows for wide interpretation– Adjuvant RT not routinely recommended– Use of imaging, RT, and ADT are at clinician discretion

Treatment Guidelines

pT3, +marginsPSA undetectable(Node negative)

RT or observation

PSA detectable Consider: Bone scan, CT/MRI/US, PSA DT, biopsyIf no distant disease: RT +/- ADT, or observation

UCMC Post-op RT Guidelines

• Post-op RT and choice of dose, volume, ADT: consider risk factors, comorbidity, and patient preference

Proposed Treatment Guidelines

pT3, +marginsPSA ≤ 0.05(Node negative)

64 Gy at 2/fx IMRT to prostate bedFavor adjuvant > salvage RT in highest risk, younger patients with reasonable urinary recovery

PSA detectable(Node negative)

Enroll on RTOG 0534; otherwise 68 Gy (2/fx) IMRT to the prostate bedIf unfavorable:50.4 Gy (1.8/fx) IMRT to pelvic lymph nodes68.4-72 Gy (1.8/fx) IMRT to the prostate bed4 months of ADT

Node positive 50.4+ Gy (1.8/fx) IMRT to pelvic lymph nodes68.4 Gy (1.8/fx) IMRT to the prostate bed4+ months of ADT

Contouring: Prostate bed

• RTOG guidelines are online for prostate bed and pelvic LNs

• Guidelines have been proposed by 4 groups– Differences mainly regard coverage of anterior

and superior prostate bed

Wiltshire, IJROBP 2007

PMH

Planning guidelines• DVH relationships are much less established for

the post-op setting compared to the intact setting– RTOG 0534:

Metric Goal

PTV V100 ≥95%

Dmax 115%

Rectum V65 Gy ≤35% (+10)

V40 Gy ≤55% (+10)

Bladder (minus CTV) V65 Gy ≤50% (+7.5)

V40 Gy ≤70% (+7.5)

Femoral heads V50 Gy ≤10%

– DVH relationships may eventually be determined using prospectively recorded late toxicity

IGRT• How much does the prostate bed move?

– Study of prostate bed beacon transponders (n=20)– Suggested margins based on setup error:

LR SI AP

Skin markings 0.9 cm 1.3 cm 1.5 cm

Bony anatomy 0.5 cm 1.3 cm 0.9 cm

– Real time tracking• >5 mm motion in 32% for >1 sec, and 11% for > 30 sec

(of 638 treatments)• 18 of 20 patients with at least one such episode (90%)

• Setup uncertainty can be significantKlayton, IJROBP 2012

IGRT optionsComments

Bony anatomy Most widely available imaging modalityOccasional patient may have widely varied setup; PTV margin ~ 0.6-1.5 cm not always reliable

Ultrasound Readily adjust for bladder filling; No additional radiation exposureInter-observer variability in setup

Surgical clips or fiducial markers in prostate bed (kV)

Can be easily seen and quickly imagedDoes not evaluate soft tissue anatomy

Cone beam CT See entirety of prostate bed volumeMore time on treatment table

On treatment imaging• IGRT can be valuable: differential rectal filling

Differential rectal filling

Daily cone beam CTReference (CT simulation)

On treatment imaging• IGRT can be valuable: differential bladder filling

Setup to prostate bed requires a 2 cm bony anatomy shift

urination

Prostate bed and bones are aligned as on CT simulation

Differential bladder filling

Daily cone beam CT #1 Daily cone beam CT #2

Conclusions: EBRT for postop prostate• Adjuvant RT is better than watchful waiting for

men with pT3, +margins• Early salvage RT (if needed) is an alternative to

adjuvant RT• Salvage RT is moderately effective, and could

impact biochemical control and survival• Uncertainty regarding timing of RT, and best

use of dose, volume, ADT will hopefully be addressed with future trials

Post-test question1. There are now 3 randomized studies testing adjuvant RT vs. observation for men with pT3 prostate cancer or positive margins after radical prostatectomy, each with >9 years of follow-up. Which of the following studies demonstrate a survival benefit?

A. EORTC 22911 (Bolla)B. SWOG 8794 (Thompson)C. ARO 9602 (Wiegel)D. RTOG 9601 (Shipley)

Post-test question2. A 71 year old man with minimal comorbidity who presents with clinical T3, intact adenocarcinoma of the prostate, Gleason score 4+4, and PSA 22 should be treated with RT/ADT rather than ADT alone because: A. Biochemical failure at 10 years is ~75% with ADT alone, and only ~50% with RT/ADTB. Cause specific survival at 10 years is reduced by half (~24% with ADT alone, and ~12% with RT/ADT)C. Overall survival at 10 years is improved by ~5% (~65% with ADT alone, and ~70% with RT/ADT)D. All answers are incorrect; ADT alone is preferred because this man is >70 years old