Urinary Adverse Events after Radiation Therapy for Prostate Cancer

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 months 4.7% 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 Stream Urgency/frequency Nocturia Dx: Bladder Outlet Obstruction Detrusor Overactivity Rec: Cystoscopy Alpha 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 baseline Median time to start of trospium 23.4 months 80% 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 months 7 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 Observation 1Urethral stricture at 5 years Risk Difference Weight Risk Difference n/n n/n M-H,Fixed,95%CI M-H,Fixed,95%CI 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) 2Urethral stricture at 10 years SW OG 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: Chi 2 =4.88, df =1(P = 0.03), I 2 =80% -0.2-0.1 0 0.1 0.2 Favoursadjuvant RT Favoursobservation

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

IPSS LUTS 72 year old with new-onset LUTS post IMRT > 3 years ago 16 14 12 10 8 6 4 2 0 0 10 20 30 40 50 60 70 Months

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

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