Prostate Support Group

Dr Duncan McLaren

Consultant Oncologist

Presentation

• Radiotherapy results• Current RT dose• IGRT• IMRT- Rapid arc• HDR• Q&A session• New Drugs• Q&A

Some good news

Improved cause specific survival with radiotherapy over the last 30 years

2001-6

1996-01

1982-9235%

70%

80%

Some good news

2001-6

1996-01

1982-9250Gy

52.5Gy

55Gy

Effect of dose escalation

55Gy

52.5Gy

P=0.0086

Time to PSA relapse years

80%

60%

T1-2b Gleason 6 PSA<10

55Gy

52.5Gy

Time to PSA relapse Years

P<0.0001

70%

40%

T2c or Gleason 7 or PSA >10

55Gy

52.5Gy

Time to PSA relapse Years

P<0.0001

40%

20%

T3 or PSA >20 or Gleason grade >8

ALPHA

BETA

DOSE per fraction

SF

Alpha/Beta for tumour = 10

Alpha/Beta for prostate tumour =1.5-3.0

Alpha/Beta for normal tissue = 5

Prostate

Tumour

Normal tissue

2Gy per day

3Gy per day

Why dose such a modest dose escalation work !

2 3 4

Advantages of Hypo-fractionation

• Shorter number of treatments– Benefits patients and machine capacity

• Possible reduced acute toxicity– CHHiP toxicity data supports this

• Possible improved efficacy– CHHiP outcome data awaited– In house data very supportive

Potential disadvantages

• If alpha beta ratio is wrong then a lower dose is given

• It may increase late damage on the rectum or bowel– No evidence of this with in house data

• Need to deliver dose very accurately IGRT conformal XRT or IMRT

Current XRT schedules

• Hypo-fractionation• 57Gy in 19# • 3Gy per day• 74Gy equivalent

• 60Gy in 20# future dose• 78Gy equivalent

• Standard fractionation• 74Gy in 37#• 2Gy per day• Can treat pelvic nodes

• Future dose 78Gy

Image Guided Radiotherapy IGRT 2009

Fiducial Markers

Inserted trans rectally

Images true prostate position and software calculates how much to move the field to correct for it

Why we can increase our doses safely

Advantages over conformal XRT

Much tighter dose to the prostate

Reduced dose to normal tissue

Further dose escalation

Disadvantages

Prostate movement

Time consuming

Irradiated volume

Intensity modulated radiotherapy IMRT

New for 2012! Even better XRT!

Varian Novalis Trilogy Linear Accelerator with Rapid Arc

Faster, reduced dose to normal tissues, greater patient throughput and can be used as a standard linear accelerator

2012 research project to use Multi-parametric MRI to fuse with planning CT scan to allow potential prostate tumour boost dose

What is happening in Prostate Brachytherapy?

Low dose rate

Permanent Iodine 125 seeds

High dose rate

Temporary Iridium 192

Single stop intraoperative prostate Seeds Brachytherapy

Live since 2010

First 150 men @ 5yrs

P=0.0005

95%

80%

55%

poor

Int

good

5 year outcomes

5 yr PSA

RFS52.5Gy 55Gy Brachy 57-60Gy

verses 74Gy

GOOD 60% 80% 95% ?

INT 40% 70% 80% ?

POOR 20% 40% 55% ?

How to improve outcome for high risk disease

• Single fraction of HDR brachytherapy and 13 fractions of external beam

External beam

Brachytherapy

HDR High dose rate prostate brachytherapy

Business case 2012

Advantages

Very high dose boost single 15Gy fraction

Flexibility to ensure dose constraints to rectum and urethra are met by adjusting catheter or source position

Reduced irradiated volume

13 fractions of XRT 2 weeks later

2 Gy equivalent dose >100GyDisadvantages

Relatively medically labour intensive

GA or spinal

Possible overnight stay

New drugs in metastatic prostate cancer

How does hormone blockade work?

ZOLADEXCASODEX

LHRH agonists

Degarelix – GnRH antagonist

240mg given as 2 subcutaneous injections of 120mg each (loading)Followed by 80mg maintenance every 28 days

Degarelix - Firmagon

SMC approval for advanced prostate cancer January 2011Locally used for high risk patients with high PSA and very symptomatic e.g. SCCMajor benefit is lack of testosterone flare

Abiraterone mode of action - Cyp -17 blocker

Blocks intra- tumour androgens

Blocks body

androgens

Abiraterone 14.8 mths OS

Placebo 10.9 mths OS

Abiraterone Phase III trial results

HR 0.65

Median Survival benefit = 3.9 months

MDV 3100 AFFIRM TrialAndrogen receptor signalling blocker

Results not yet published but trial closed December 2011

OS 18.4 months MDV 3100

OS 13.6 months placebo

HR 0.63

Median survival benefit 4.8 months

Alpharadin- Radium 223

ALYMPSA Trial post Taxotere progression

16.3 mths

11.5mths

Median survival benefit 4.8 months

Cabazitaxel v Mitoxantrone post Taxotere progression- TROPIC Trial

Median survival 15.1 mths Cabazitaxel v 12.7 mths Mitoxantrone p=0.04

positive results does not = NHS funding

Median survival benefit 2.4 months

Thank you