Radiation Therapy in Prostate CancerCurrent Status and New Advances
Mahdi Aghili MD ,AFSACancer Institute -Department of Radiation Oncology
Associated Professor of Tehran University of Medical Sciences2/11/1390
HISTORY OF RADIATION THERAPY IN PROSTATE CANCER
Radiation Modalities
External Beam →Involves the use ofphotons andelectrons
←Brachytherapy“Close therapy”Radioactive sources placedwithin the prostate
History of RT in Prostate Cancer
Early Prostate Brachytherapy
Prostate Implant (1917)
•Recognized that asuperior approach wouldbe to insert radium needlesdirectly into the prostate•More of the prostate couldbe treated with lessdamage to the urethraRadiation Therapy and Prostate Cancer
Prostate BrachytherapyUrology Textbook (1926)
Radiation Therapy in Prostate Cancer
• Enthusiasm for brachytherapy and RT in general decreased after World War II• Many patients were not cured• Mainstay of treatment became surgery• Excitement also surrounded discovery of
the hormonal therapy
Prostate Brachytherapy
• Newer techniques allow seeds to be better distributed throughout the prostate
• Interest decreased today with permanent seed implants due to urinary side effects and advances in external beam RT
Radiation Therapy in Prostate Cancer
• Interest returned in the 1960s• Development of megavoltage (high energy
machines)• Highly penetrating beams which treat the prostate• without excessive skin toxicity
Malcolm BagshawStanford University
Demonstrated that prostatecancer is curable withexternal beam(megavoltage) RT
External Beam Treatment Machines1920’sLow energyPoor penetrationUnable to treat the prostate without skin toxicity
1950sModerate EnergyImproved penetrationLess skin toxicity
TodayComputer controlled Linear acceleratorsMultiple high energy beamsIMRT and IGRT
External Beam Treatment
• Advancing rapidly• Better, more powerful machines• New sophisticated approaches- Intensity Modulated RT (IMRT)- Image-Guided RT (IGRT)- Proton Therapy
RADIATION TECHNIQUES
External Radiotherapy ( Teletherapy )
• The radiation source outside of body
• Fractionated • Higher integral dose • Conventional or newer
technology (3D conformal ,IMRT &proton beam)
• 66-81 Gy depend to radiation technique
Conventional vs. IMRT
IMRT in Prostate Cancer
• Better focusing allows us to reduce risk of toxicity to rectum and bladder
• Also allows us to safely use higher doses to improve cure rates
• Also being used to potentially reduce risk of impotence by reducing irradiation of the penile bulb
IMRT
MLC Segments
Intensity Map
IGRT
Prostate Movement during 8 minutes
One slice each 5 seconds
Image Guided RT (IGRT)
• Current interest focused on image guided RT (IGRT)• Method to use imaging in the treatment
room to improve the delivery of IMRT• Not a replacement for IMRT• IMRT focuses the radiation on the
prostate while IGRT ensures that it is aimed correctly everyday
Small gold seeds implanted in prostate• IGRT system used to match position everydayA more sophisticated method is to perform daily CT• Used to ensure proper alignment of prostate
Tomotherapy
• RT is delivered slice-by-slice
• is a form of Computer Tomogeraphy (CT) guided Intensity Modulated RadioTherapy (IMRT)
Cyberknife Radiosurgery• frameless robotic
radiosurgery system • Small linear accelerator
and a robotic arm• Total body radiosurgery• Image guided• Multiple shuts of RT
beams• 1-5 fractions
Modern Brachytherapy
I-125 seed
Quality of life after seed implants
• Morbidity Incidence Mean duration
• Difficulty urinating 80-95% 6-24 months
• Urinary retention 12% 2 weeks
• Urinary Incontinence <1-2%
• Rectal bleeding ?
• Impotency 30-40%
Seed Summary
• Convenient out patiant treatment for early postate cancer
• As effecting that removing the prostate
• Less side effects
Why HDR
• Seeds are permanent• Needle tracks not straight• Difficult to get adequate dose in periprostatic
tissue
HDR Prostate Brachytherapy
• Practical advantage• Physical advantage• Biological advantage
HDR vs. LDR• Practical advantage• - No worries re : Seed Supply.• - No worries re : Lost Seeds.• - No worries re : Radiation Exposure.• - No worries re : Seed Migration.• - No worries re : Seed Emboli.• - No worries re : Pre-Plan Matching.• - No worries re : EPE.• - No worries re : SVI• - No worries re : Pubic Arch.• - No worries re : Volume.
RADIOTHERAPY (INDICATIONS AND RESULTS)
Radiotherapy
• There are no randomized studies comparing radical prostatectomy (RP) with RT either EBRT or BT for localized prostate cancer
• External irradiation offers the same long-term survival results as surgery; moreover, EBRT provides a quality of life at least as good as that provided by surgery*
*the National Institutes of Health (NIH)-1988
• In daily practice, a minimum dose of > 74 Gy is recommended with short-term androgen deprivation therapy (ADT) is recommended (based on the results of a phase III RCT)
• Higher Dose RT provide a significant increase in 5-year freedom from clinical or biochemical failure for patients in an intermediate-risk group
- Dutch Trial :68 Gy with 78 Gy- MRC RT01 study: 64 Gy with 74 Gy- MD Anderson study specially in high risk group
Dose Escalation for HR PcaDose escalation protocols showed that better
BRFI and local control specially in high risk group- Dose radiation by 10% can increase local control
by 20%- 3D Conformal, IMRT, HDR Brachytherapy boostHigher dose fractions may improve disease
specific survivalHDR has lower margin of healthy organ than
IMRT and 3D-CRT
Result of dose escalation in HR and LR groups
Dose Escalation
• In cases of intermediate- or high-risk localised PCa, brachytherapy in combination with supplemental external irradiation or neoadjuvant hormonal treatment may be considered
• Compared to EBRT alone, the combination of EBRT and HDR brachytherapy showed a significant improvement in biochemical relapse free survival (p = 0.03)
Late effects • the prospective EORTC randomised trial 22863 (1987-
1995) :- ≤ 70 Gy with older RT techniques• 90% of patients were diagnosed as stage T3-4• 91% evaluated for urinary or intestinal complications or leg
oedema• 19% grade 2 , 3.8% grade3 and 1% deathNewer techniques (3D-CR & IMRT )• Recent data from MSKCC: grade 2 or more GI toxicity was 5%
with IMRT, compared with 13% with 3D-CR and for late GU toxicity was 20% in patients treated with 81 Gy, compared with 12% in patients treated with lower doses
Incidence of late toxicity by RTOG grade Toxicity
(from EORTC trial 22863)
Impotency• Radiotherapy affects erectile function to a lesser degree
than RP according to retrospective surveys of patients• A recent meta-analysis has shown that the 1 and 2
year rate of probability for maintaining erectile function:
- brachytherapy :0.76 and 0.70- ERT+ BT:0.60 and 0.60- External irradiation:0.55 and 0.52- nerve-sparing RP:0.34 and 0.25- Standard RP:0.25 and 0.25
ADJUVANT OR SALVAGE RT
Adjuvant RT• Immediate post-operative for pT3• 3 RCT have assessed the role of immediate post-operative
radiotherapy- EORTC trial (1005 pts): pT3 pN0 with risk factors R1 and
pT2R1 after RP immediate post op 60 Gy or 70 Gy after PSA rising: improves 5-year clinical or biological survival: 72.2% vs 51.8% (p < 0.0001) , and 3% survival benefit after 10 yrs ,risk of grade 3-4 GU toxcisitiy <3.5%
• ARO trial 96-02(385 pts): improvement in BFS of 72% versus 54% respectively (p = 0.0015)
• SWOG 8794 trial(425pts):in pT3 patients with median follow-up of more than 12 years ; adjuvant radiation significantly improved metastasis-free survival, with a 10-year metastasis-free survival of 71% versus 61% (median: 1.8 years prolongation, p = 0.016)
• 10-year overall survival of 74% versus 66% (median: 1.9 years prolongation, p = 0.023)
Adjuvant RT• Patients with pT3 pN0 have a high risk of local failure
after RP due to positive margins (highest impact), capsule rupture, and/or invasion of the seminal vesicles, who present even if with a PSA level of < 0.1 ng/mL
• two options can be offered to pT3- Either an immediate radiotherapy to the surgical bed
upon recovery of urinary function;• or clinical and biological monitoring followed by salvage
radiotherapy when the PSA exceeds 0.5 ng/ml• so providing patients with the chance of about 80%
being Progression free 5 years later
Salvage treatment• 1) After Radical Prostatectmy- Usually define by PSA rising- RT may curable in 50% of patients specially if PSA<1.5
ng/ml- ERT 66-70 Gy to prostate bed- Hormon therapy ??• 2)After External RT - PSA rising in absent of regional or distant mets- Should be confirmed by biopsy or MRI-MRS- Hormontherapy, Brachytherapy(seed or HDR), Surgery,
Cryotherapy or HIFU
Salvage treatment after Radiotherapy
BRFS(5 yrs) Complications• Salvage Surgery 44-65% Incontinence 40% Stricture 25%
• Cryotherapy 58% Incontinence 15% fistula 10% rectal and perineal pain35%
• HIFU 10-50% Stricture 11%, rectal fistula up to66%
• Brachytherapy 34 -75% (LDR) Incontinence 6%,GU (G3-4)17% 89% (2 yrs for HDR) GI 7%
Conclusion
• Radiotherapy is a good option as surgery in early stage prostate cancer with acceptable long term results and complications
• Newer techniques 3D-CRT, IMRT, IGRT, SBRT , Brachytherapy improved local control and reduced complications