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Radiation Oncology/Toxicity/Erectile dysfunction

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Erectile Dysfunction


Assessment tools

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  • International Index of Erectile Function (IIEF) - Sexual health inventory for men
    • Original 15-item questionnaire (IIEF-15):
      • PMID 9187685, 1997 — "The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction." Rosen RC et al. Urology. 1997 Jun;49(6):822-30.
    • 5-item questionnaire (IIEF-5):
      • Score range 5-25. Severe 5-7, moderate 8-11, mild to moderate 12-16, mild 17-21, no ED 22-25.
      • PMID 10637462, 1999 — "Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction." Rosen RC et al. Int J Impot Res. 1999 Dec;11(6):319-26.
      • PMID 12152112, 2002 — "The use of the simplified International Index of Erectile Function (IIEF-5) as a diagnostic tool to study the prevalence of erectile dysfunction." Rhoden EL et al. Int J Impot Res. 2002 Aug;14(4):245-50.
      • Form: PDF from www.njurology.com and Online version - at medal.org

Prostate Cancer

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  • ICORG 97-01; 2012 (1997-2001) PMID 22682750 -- "The effect of short term neo-adjuvant androgen deprivation on erectile function in patients treated with external beam radiotherapy for localised prostate cancer: an analysis of the 4- versus 8-month randomised trial (Irish Clinical Oncology Research Group 97-01)." (Daly PE, Radiother Oncol. 2012 Jul;104(1):96-102.)
    • See page at Adjuvant ADT
    • Conclusion: "The first year post ADT and EBRT poses the greatest risk to sexual function and a continued decline may be expected. However, 26% of men can expect to retain sexual function at 5 years."
  • Beth Israel / Harvard; 2011 (2003-6) PMID 21934053 -- "Prediction of erectile function following treatment for prostate cancer." (Alemozaffar M, JAMA. 2011 Sep 21;306(11):1205-14.)
    • Longitudinal multicenter cohort study. 1027 pts treated with RP, BT, or RT. Developed models predicting erectile function at 2 yrs after treatment based on patient characteristics, sexual HRQOL, and treatment characteristics.
    • 37% of all pts and 48% of those who were potent before treatment remained potent at 2 yrs after treatment. 53% of pts reported use of medications for treatment of erectile dysfunction. Models were externally validated in a separate cohort.
    • Conclusion: a model was developed to estimate risk of ED after treatment

Brachytherapy

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  • University of Washington; 2009 (2001-2003) PMID 19303721 -- "Erectile function durability following permanent prostate brachytherapy." (Taira AV, Int J Radiat Oncol Biol Phys. 2009 Nov 1;75(3):639-48. Epub 2009 Mar 21.)
    • Retrospective. 226 patients, treated with brachytherapy in 2 prospective randomized trials. Potency defined using IIEF-6 score. Median F/U 6.4 years
    • Outcome: 7-year potency rate 56%. By baseline potency score (2004 vs. 2008): 29-30: 75% vs 74%, 24-28: 52% vs. 45%, 18-23: 48% vs. 40%, 13-17: 23% vs. 23%. Multivariate predictors were preimplant IIEF score, HTN, DM, prostate size, dose to proximal penis
    • Dosimetry: Penile bulb D25 <50% 71% vs. >50% 45% (SS); highest impact in mild baseline dysfunction (IIEF score 18-23), where D25 <50% potency 73% vs. >50% 14% (SS)
    • Conclusion: Potency preservation is durable following brachytherapy; penile bulb sparing may further improve it

Penile Bulb Dose

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  • RTOG 9406; 2004 PMID 15590164 -- "Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: findings from a prospective, multi-institutional, phase I/II dose-escalation study." (Roach M, Int J Radiat Oncol Biol Phys. 2004 Dec 1;60(5):1351-6.)
    • Subset analysis, 158 men potent at entry
    • Outcome: "Remained potent" if median dose <52.5 Gy 68% vs. >52.5 Gy 52%; "Became impotent" 32% vs. 48%. Median dose to penile bulb if "remained potent" 49.8 Gy vs. "became impotent" 60.3 Gy. In MVA, age, dose to prostate, ADT correlated with risk of impotence
    • Conclusion: Dose to penile bulb associated with risk of radiation-induced impotence


Meta-Analysis

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  • Robinson; 2002 PMID 12419432 -- "Meta-analysis of rates of erectile function after treatment of localized prostate carcinoma." (Robinson JW, Int J Radiat Oncol Biol Phys. 2002 Nov 15;54(4):1063-8.)
    • Meta-analysis. 54 studies including brachytherapy, brachytherapy + EBRT, EBRT alone, standard RP and nerve-sparing RP, cryotherapy


Proportion with Erectile Dysfunction
Therapy 1-year 2+ years Age-adjusted
Brachytherapy 24% N/A 20%
Brachytherapy + EBRT 40% 40% 31%
EBRT alone 45% 48% 32%
Radical Prostatectomy, Standard 75% 75% 84%
Radical Prostatectomy, Nerve-sparing 66% 75% 78%
Cryotherapy 87% 85% 87%

Treatment

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Treatment of ED in patients treated with RT for prostate cancer

Randomized:

  • RTOG 0215 -- sildenafil vs placebo
    • Randomized, double blind, placebo controlled crossover design. 115 pts treated with EBRT + hormones for localized prostate cancer. No brachytherapy. Treatment with LHRH analogue for 8-28 weeks prior to RT and during RT but discontinued at the completion of RT. Must have erectile dysfunction with answers of "no sexual activity" (score 0) to "sometimes" (score 3) on Question #1 of IIEF ("How often were you able to get an erection during sexual activity?")
      • Arm 1: treatment with sildenafil PRN 50-100 mg qd x 12 weeks; 1 week break; crossover to placebo x 12 weeks
      • Arm 2: placebo x 12 weeks; 1 week break; crossover to sildenafil x 12 weeks
    • 2011 PMID 21235716 -- "Randomized, double-blinded, placebo-controlled crossover trial of treating erectile dysfunction with sildenafil after radiotherapy and short-term androgen deprivation therapy: results of RTOG 0215." (Watkins Bruner D, J Sex Med. 2011 Apr;8(4):1228-38.)
      • Sildenafil had a positive effect. However, as few as 21% of patients had a treatment specific response, only improving during sildenafil but not during the placebo phase.
      • Conclusion: "This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer."

Prevention

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Prevention of ED in patients treated with radiotherapy for prostate cancer

Randomized:

  • MSKCC - sildenafil vs placebo
    • Double blind randomized to 1) sildenafil 50 mg vs 2) placebo, beginning 3 days prior to start of RT and continuing for 6 months. Drug was then discontinued and taken PRN.
    • 2013: (Abstract) ASTRO Abstract - Press release PDF Abstract HTML -- "Results of a Prospective Randomized Double-blind, Placebo-controlled Trial Evaluating the Use of Prophylactic Sildenafil Citrate During Radiation Therapy in the Treatment of Prostate Cancer." (Zelefsky MJ, 2013 ASTRO Annual Meeting, Int J Radiat Oncol Biol Phys Volume 84, Issue 3, Supplement , Page S2, 1 November 2012.)
      • The IIEF overall scores were significantly higher in the SC arm compared to placebo at 6 months (p = 0.006), 12 months (p = 0.02), and 24 months (p = 0.04) after therapy.
      • Conclusion: Daily SC administered during and after radiation therapy for prostate cancer resulted in improved overall sexual function compared to placebo at all time points. This is the first randomized prospective controlled trial to demonstrate the utility of a PDE5 inhibitor as a rehabilitation strategy in the prostate cancer radiation therapy patient population.
  • RTOG 0831 -- tadalafil vs placebo
    • Double blind randomized to 1) tadalafil 5 mg vs 2) placebo daily x 6 months beginning at start of RT.
    • 2013: Preliminary results ASCO Abstract 2013 -- "Preliminary results of RTOG 0831, a randomized, double-blinded, placebo-controlled trial of tadalafil in the prevention of erectile dysfunction in patients treated with radiotherapy for prostate cancer." (Bruner D, 2013 ASCO Annual Meeting, abstract 9525, J Clin Oncol 31, 2013 (suppl; abstr 9525))
      • 155 analyzable pts. Spontaneous EF at 30 wks from drug start was not different between arms based on IIEF Q1 response, total IIEF score (52.5 drug vs 52.8 placebo), or score change from baseline (-8.0 drug vs -8.8 placebo). No difference at 1 yr. About 80% of pts maintained spontaneous EF in both arms.
      • Conclusion: "Low-dose daily tadalafil did not preserve EF within the first year of RT for prostate cancer."

Management Guidelines

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