Urinary Adverse Events after Radiation Therapy for Prostate Cancer

Sexual Medicine Society of North America

Scottsdale, Arizona

2016

Jaspreet S. Sandhu, MD

Department of Surgery/Urology

Memorial Sloan Kettering Cancer Center

Disclosures

• Boston Scientific - Consultant

Outline

• Natural History of Urinary Function Recovery after Radiotherapy for Prostate Cancer

• Voiding Dysfunction after Primary Radiation Therapy

– Etiology

– Management

• Effects of Salvage/Adjuvant Radiation Therapy

• Late Effects

– Urinary Toxicity

– Secondary Malignancies

Outcomes: Expanded Prostate Cancer Index Composite (EPIC-26)

• 1643 men randomized trial comparing AS, RP, XRT

• PRO recorded at 6-months, 12-months, and yearly thereafter for 5 years

• Prostate Cancer Outcomes Study (PCOS) followed 1655 men treated with RP (1164) and RT (491) for 2, 5, and 15 years

• No significant different at 15 years

Fter

600 patients; median follow-up – 37 months4.7% underwent TURP – 17% incontinent

• AUA Symptom Score – greater than 7 associated with worse toxicity• Prostate Size > 35 ml associated with worse toxicity

• Prostate Volume and AUA symptom score predict grade 2 urinary toxicity

• IPSS, post-void residual volume, and peak flow rate predictive

Risk Factors for Adverse Urinary Function

• Multiple preoperative factors implicated for urinary morbidity after prostate radiotherapy

– IPSS (8 or greater worse)

– PVR (100 mls or greater)

– Peak Flow Rate (10 ml/sec or less)

– Prostate Volume (40 ml or more)

– BOO on urodynamics

• Intraoperative technique (dose, etc.)

Adverse Urinary Events

• Increase in LUTS – Irritative/Obstructive

– Medical management Initially

– Surgery in select cases

• Urinary Incontinence

– Rule out obstruction (often overflow)

– Stress incontinence managed like post-prostatectomy incontinence*

• Urinary Retention

– Intervention varies by type of obstruction and time from RT

• Urinary Fistulae

Objective Urinary Function after RT

Urodynamics Post-Brachytherapy

Symptoms:Weak StreamUrgency/frequencyNocturia

Dx:Bladder Outlet ObstructionDetrusor Overactivity

Rec:CystoscopyAlpha Blockers+/- TURP

Medical Therapy

• Alpha blockers mainstay

• Role for anticholinergics/ beta 3 agonists in select patients

• Injection of biological agents (won’t discuss)

Flomax

Trospium

69 patients treated for irritative symptoms (frequency, urgency, nocturia)Resolution defined as IPSS within 2 of baselineMedian time to start of trospium – 23.4 months80% resolution

Incidence of Urinary Retention after Brachytherapy

• Bimodal Distribution

– Immediately after implantation

– Delayed presentation

• Incidence

– Up to 20%

– Learning curve associated with decrease from 17% - 6%

• Prevention

– IPSS

– Prostate size

– Flow rate/post void residual

– ?Pre-procedure urodynamic parameters

Williams et al, Radiother Oncol, 2004

Keyes, et al, IJROBP, 2006

Bladder Outlet Obstruction/Urinary Retention

• Stricture versus prostatic obstruction

• Diagnosed by urodynamic testing in conjunction with cystoscopy

• Treatment

– Alpha blockers important first line

– Internal uretherotomy for stricture

– Clean intermittent catheterization (CIC)

– Suprapubic tube or indwelling catheter if unable to self-catheterize

• Refractory to medicines and at least a year after RT

– Transurethral resection of the prostate (TURP)

– Reconstruction v/s Urinary diversion (UD)

Post Radiation TURP

• Stress urinary incontinence as high as 70%

• Rate possibly reduced to ~20% with appropriate patient selection

– Urodynamically obstructed

– New onset obstruction without previous voiding symptoms

• Careful resecting posterior prostate to prevent rectal fistula

• Similarly, higher risk of pubic complications with aggressive anterior resection

• Usually dramatic improvement in voiding symptoms and urge incontinence

• Secondary TURPs

– Higher rate of rectal fistulas and incontinence

Kollmeier

38 patients treated for retention/obstructive symptoms – median 11 months7 patients incontinent (18%)

Incontinence after Adjuvant/Salvage Radiotherapy

• Urinary Incontinence higher with adjuvant compared to observational arm

– 6.8% v/s 2.6% (262 patients in each arm – EORTC/SWOG)

• 81 patients – pre- and post-op urinary function recorded

• 361 men

– 153 men received adjuvant radiotherapy between 1-6 months after surgery

– Compared to 208 men who did not

• Adjuvant RT (199) compared to Salvage RT (128) and no RT (1863)

Urethral Strictures after Adjuvant/Salvage Radiotherapy

• Urethral Stricture higher with adjuvant compared to observational arm at 10 years – no difference at 5 years

– 10% v/s 5.8% (373/359 patients in each arm – ARO/SWOG)Analysis 1.5. Comparison 1 Adjuvant RT versus nil postprostatectomy, Outcome 5 Urethral stricture.

Review: Adjuvant radiotherapy following radical prostatectomy for prostate cancer

Comparison: 1 Adjuvant RT versusnil postprostatectomy

Outcome: 5 Urethral stricture

Study or subgroup Adjuvant RT ObservationRisk

Difference WeightRisk

Difference

n/N n/N M-H,Fixed,95%CI M-H,Fixed,95%CI

1 Urethral stricture at 5 years

ARO 2/159 1/148 100.0 % 0.01 [ -0.02, 0.03 ]

Subtotal (95% CI) 159 148 100.0 % 0.01 [ -0.02, 0.03 ]

Total events: 2 (Adjuvant RT), 1 (Observation)

Heterogeneity: not applicable

Test for overall effect: Z = 0.52 (P= 0.60)

2 Urethral stricture at 10 years

SWOG 38/214 20/211 100.0 % 0.08 [ 0.02, 0.15 ]

Subtotal (95% CI) 214 211 100.0 % 0.08 [ 0.02, 0.15 ]

Total events: 38 (Adjuvant RT), 20 (Observation)

Heterogeneity: not applicable

Test for overall effect: Z = 2.51 (P= 0.012)

Test for subgroup differences: Chi2 = 4.88, df = 1 (P= 0.03), I2 =80%

-0.2 -0.1 0 0.1 0.2

Favours adjuvant RT Favours observation

42Adjuvant radiotherapy following radical prostatectomy for prostate cancer (Review)

Copyright © 2011 The Cochrane Collaboration. Published by John W iley & Sons, Ltd.

Surgical Treatment for RT Urethral Stricture

• 72 men

– Mean time from RT – 6.4 years

– Mean length of stricture – 2.3 cm

– 92% underwent EPA

– 70% success at mean 3.5 years follow-up

Late Effects

• Late Urinary Toxicity

• Urinary Fistulae

• Secondary Malignancy

– Sarcoma

– Bladder Cancer

– Rectal Cancer

• Radio-Resistant Prostate Cancer

LUTS

• 72 year old with new-onset LUTS post IMRT > 3 years ago

0

2

4

6

8

10

12

14

16

0 10 20 30 40 50 60 70

Months

IPS

S

Infection• Can occur anytime

• Diagnosed by tender prostate on rectal (with or without positive urine culture)

– Urine and Semen cultures helpful in tailoring antibiotics

• Often prostate not tender and no growth on cultures in patients with RT

• Treatment

– Long term course of antibiotics (Fluoroquinolones have excellent prostatic

penetration)

– Suprapubic tube if no resolution in a few days

– Possible transrectal ultrasound or CT/MRI to rule out abscess

Prostate Abscess

• Unroof via TURP – Gold Standard

• Possible role for transperineal/transrectal aspiration

Urinary Fistulae

• Often due to Endoscopic manipulation of radiated tissue

– Rectal fistula secondary to colonoscopic or cystoscopic intervention

– Pubovesical fistula/sinus

Fistula - Angermeier

• 45 patients – 29 with previous RT/ablative therapy

• Definitive repair in 15/16 (94%) versus 6/29 (21%)

• Success in 13/15 (87%) versus 1/6 (17%)

Pubo-Vesical Fistulae

• Likely secondary to aggressive treatment of AS

– Presents with suprabupic pain/osteitis

– +/- UTIs

– Usually after RT

– Conservative measures include long course of antibiotics with foley/PCNS

– Possible role of HBO

– Only definitive treatment to prevent recurrent UTI’s is cystectomy/diversion

Secondary Malignancies

• 100 consecutive patients

Salvage RP

• 50% rate of urinary incontinence

– Suggestion that it is lower in recent series (Learning curve)

– Attempts being made to decrease this rate

• 20-30% rate of anastomotic stricture

• 1-5% rate of recto-vesical fistula formation

RT induced Urinary Dysfunction Summary

• Diverse etiologies for voiding dysfunction after prostate radiation

– Important to know natural history

• Management varies by time from RT

– Medical (alpha blockade +/- anticholinergics)

– Surgical (particularly for BOO)

– Don’t forget late effects

Thank You