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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
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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