Dr Hamid Reza Dehghan Manshadi

Radiation Oncologist

Shahid Beheshti University of Medical Sciences

Prostate Radiotherapy A-Z

Clinical (cT) T0 No evidence of primary tumor T1 Clinically inapparent tumor neither palpable nor visible by imaging T1a Tumor incidental histologic finding in 5 percent or less of tissue

resected T1b Tumor incidental histologic finding in more than 5 percent of tissue

resected T1c Tumor identified by needle biopsy (eg, because of elevated PSA) T2 Tumor confined within prostate* T2a Tumor involves one-half of one lobe or less T2b Tumor involves more than one-half of one lobe but not both lobes T2c Tumor involves both lobes T3 Tumor extends through the prostate capsule• T3a Extracapsular extension (unilateral or bilateral) T3b Tumor invades seminal vesicle(s) T4 Tumor is fixed or invades adjacent structures other than seminal vesicles

such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall

Distant metastasis (M)§ M0 No distant metastasis M1 Distant metastasis M1a Nonregional lymph node(s) M1b Bone(s) M1c Other site(s) with or without bone disease

Staging

TNM anatomic stage prognostic groups for prostate cancer*

Stage (T) (N) (M) PSA Gleason I T1a-c N0 M0 PSA <10 Gleason ≤6 T2a N0 M0 PSA <10 Gleason ≤6 T1-2a N0 M0 PSA X Gleason X IIA T1a-c N0 M0 PSA <20 Gleason 7 T1a-c N0 M0 PSA ≥10<20 Gleason ≤6 T2a N0 M0 PSA <20 Gleason ≤7 T2b N0 M0 PSA <20 Gleason ≤7 T2b N0 M0 PSA X Gleason X IIB T2c N0 M0 Any PSA Any Gleason T1-2 N0 M0 PSA ≥20 Any Gleason T1-2 N0 M0 Any PSA Gleason ≥8 III T3a-b N0 M0 Any PSA Any Gleason IV T4 N0 M0 Any PSA Any Gleason Any T N1 M0 Any PSA Any Gleason Any T Any N M1 Any PSA Any Gleason

• Low risk — Clinical stage T1c or T2a AND a serum PSA <10 ng/mL AND a biopsy Gleason score ≤6 (anatomic stage prognostic group I)

 • Intermediate risk — Clinical stage T2b OR a serum PSA between 10 and 20 ng/mL OR a biopsy Gleason score 7 (anatomic stage prognostic group IIA)

 • High risk — Clinical stage T2c disease OR a serum PSA >20 ng/mL, OR a biopsy Gleason score ≥8 (anatomic stage prognostic group IIB)

Risk stratification

RADICAL PROSTATECTOMY Indications : T1,/T2 some T3 Side Effects : Urinary incontinence,

Impotence EBRT : Indications : T1/T4 Conformal, 3D , IMRT Brachytherapy : LDR (Seeds) HDR (Ir 192)

Treatment shedules

Indications

Treatment optionsfor localized prostate cancer

The Urologist’ s point of viewby country ? by hospital? by specialty ?

Differences in patients:age (biologic), condition, QL--issues…

Differences: individual patient:Anatomy,, erectile function…

Patient selection / EducationCure potentials, Treatment Options

BT advantages : PTV = CTV - Real dose escalation (144 Gy) - Fast treatment (/ERT) - Low impotency rate (<RP and ERT) - Low rectitis rate (/RTE) - Low urinary complications (/RP)

Equivalence between BT / EBT and Radical Prostatectomy

Radioprotection – no free live sources – no risk of source loss – no radioprotection issues after

discharge

Cheap: utilises existing HDR source and equipment

In some centers may be outpatient procedure

Practical advantages of temporaryHDR prostate brachytherapy

• Brachytherapy enables localized high dose with reduced dose to critical normal tissues

– rectum, bladder, small bowel

• Uses volume definition after implant; can be customised to individual volume with no organ movement.

Can implant larger volume than permanent implant with certain dose delivery including extracapsular region and seminal vesicles

Physical advantages of temporaryHDR prostate brachytherapy

HDR implant: volume definition

HDR implant: biological advantage2Gy EQD

Inclusion criteria Tumor stages T1-T3b Tumor invasion of bladder neck Any Gleason score Any PSA level Prostate volume ≤60-80 cc Possible exclusion criteria Distant metastases Life expectancy <5 y Substantial urinary obstruction Inability to implant entire prostate Patient unfit for anesthesia TURP within previous 6 mo Rectum-prostate distance <5

mm

Selection Criteria for Using HDR Brachytherapy in Patients With Prostate

Cancer

HDR As Boost To EBRT: Stage >=T2B or, PSA>10 or

GS>=7(intermediate/ Highrisk HDR As Monotherapy: Stage =<T2a and PSA=< 10 and GS=<7

(low risk HDR As Salvage (up To 76 Gy) No Mts, Biopsy confirmation, PSA relapse,

Antianrogen resistance or intolerance

Indications and Patient selection for HDR-Brachytherapy(GEC- ESTRO)

Recommendations

Indications for HDR prostatebrachytherapy BOOST

• CTV1: whole gland defined by capsule– Margin around capsule may be added 3 –5

mm

• CTV2: peripheral zone

• CTV3: GTV

• PTV = CTV

CTV criteriaGEC ESTRO guidelines

• Urethral dose <10Gy per fraction

• Rectal dose <6Gy per fraction

OAR criteriaGEC ESTRO guidelines

– Highest overall BED

– Includes advantages of regional irradiation by external beam

– Includes advantages of conformality with HDR including extracapsular and seminal vesicle areas

– Optimal therapeutic ratio

– Dose delivery reliable

Intermediate risk prostate cancerExternal beam +HDR boost

HDR Boost :PTV= CTV1 45Gy EBRT + 2 implants (10.5 Gy*2) BED >94-100 HDR Monotherapy : PTV=CTV1 2 implants , 2* 9.5 Gy/implant total 38 Gy

in 2 weeks BED =100 Gy HDR Salvage : 4 implants * 6 Gy = 24 Gy in 12 weeks

Dose and Fractions

HDR Boost : Late toxicity : Rectum EBRT (76 Gy ) EBRT+HDRBoost(86Gy) Grade 0 81% 96% Grade 1 6.7% 1.3% Grade 2 12.5% (Bleeding) 2.7 % Grade 3 0.4% --

Bladder Grade 0 91% 90% Grade 1 1.3% 1.8% Grade 2 8.5% 8.5% Grade 3 -- -- EBRT + Boost : Less Failure, Less

Toxicity

Results

Brachy (a) RRP XRT Urethritis 5% N/A 3% Stricture 6% 5% 6% Incontinence <1% 5 (b) - 30 (c) % 1% Rectal/proctitis 5% N/A 9% Impotence: < 60 10% 25% d

60 – 70 20% 35% d vs. 70% (e) 30% > 70 40% 50% d

(a) No pre-implant TURP (b) Center of excellence

(c) Population studies (d) Nerve sparing

(e) Non-nerve sparing

LONG-TERM COMPLICATIONS ?

Target Volume Delineation

HDR brachytherapy is an established technique enabling high dose delivery to prostate gland

HDR brachytherapy has potential advantages especially for more advanced prostate cancer

– Physical implant flexibility – Biological advantage of large fractions

HDR Monotherapy forLocalised Prostate Cancer

HDR monotherapy is feasible and can deliver 4 fractions over 3 days with one implant procedure

Acute toxicity is limited to transient urinary disturbance, returning to baseline at 12 weeks

Early biochemical results for advanced disease are encouraging. Further dose escalation is possible or necessary

HDR Monotherapy for Localised Prostate Cancer Conclusions

Foley catheter removed on Day 2 No residual pain Recommandations/information Acute effects Irritation syndrome Retentionnal syndrome Radiation hazards

Post operative follow up

HDR Monotherapy : OS; 98.9% ,PSA Specific control :100%,

Biochemical control : 97.2% GU Toxicity GI Toxicity Grade0 34% 96.4% Grade 1 52% 3.6% Grade 2 3.3% -- Grade 3 9.8% --