Evaluating the relationship between erectile dysfunction and dose received by the penile bulb: Using data from a randomised controlled trial of conformal radiotherapy in prostate cancer (MRC RT01, ISRCTN47772397)

Academic Department of Radiotherapy and Oncology, The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, Sutton, Surrey, UK.
Radiotherapy and Oncology (Impact Factor: 4.36). 09/2006; 80(3):355-62. DOI: 10.1016/j.radonc.2006.07.037
Source: PubMed


To evaluate the relationship between erectile function and the radiation dose to the penile bulb and other proximal penile structures in men receiving conformal radiotherapy (CFRT) for prostate cancer (PCa).
The Medical Research Council (MRC) RT01 trial randomised 843 men who had localised PCa to receive either 64 or 74 Gy after 3 - 6 months neoadjuvant hormonal treatment. Fifty-one men were selected who were potent prior to hormonal treatment, having completed both pre-hormone and 2-year post-CFRT Quality of Life assessments, and on whom dose volume data were available for analysis. The men were divided into three groups according to 2-year follow-up: potent, reduced potency, and impotent. The bulb of the penis together with the crura, were outlined on restored treatment plans. Dose - volume histograms were generated and compared between the three groups. An ordered logistic regression model was used to calculate the odds ratio of a range of dose - volume parameters to the penile bulb and effect on erectile dysfunction. The dose to the penile bulb was correlated to the dose received by the crura.
Of the 51 patients, 12 remained potent, 22 had reduced potency, and 17 were impotent at 2 years. No differences were seen in mean dose to the penile bulb by allocated treatment (t test = 1.61, p = 0.11). The mean doses to the penile bulb received by the potent, reduced potency, and impotent groups were 45.5 Gy (SD 17.1), 48 Gy (SD 16.1), and 59.2 Gy (SD 13.8), respectively. There was a strong correlation between the mean dose received by the penile bulb and dose to the crura (r = 0.82, p < 0.0001). 83.3% of impotent patients received a D90 > or = 50 Gy to the penile bulb compared with 29.4% of patients who maintained potency at 2 years (p = 0.006).
There is evidence from this study to suggest a dose volume effect on the penile bulb and erectile dysfunction. A D90 > or = 50 Gy is associated with a significant risk of erectile dysfunction and this should form a basis for selecting dose constraints in future dose escalation studies.

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    • "Van der Wielen et al. studied the correlation between ED and dose to penile bulb in patients treated with doses of 68–78 Gy: but there was no relation found [149]. Mangar et al. demonstrated that a dose received by 90% of the penile bulb (D90) >50 Gy was significantly associated with ED (P = 0.006) [150], results comparable to the outcomes of the study of Wernicke et al. [151]. "
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    ABSTRACT: Prostate cancer (PCa) is the most common malignancy in elderly men. The progressive ageing of the world male population will further increase the need for tailored assessment and treatment of PCa patients. The determinant role of androgens and sexual hormones for PCa growth and progression has been established. However, several trials on androgens and PCa are recently focused on urinary continence, quality of life, and sexual function, suggesting a new point of view on the whole endocrinological aspect of PCa. During aging, metabolic syndrome, including diabetes, hypertension, dyslipidemia, and central obesity, can be associated with a chronic, low-grade inflammation of the prostate and with changes in the sex steroid pathways. These factors may affect both the carcinogenesis processes and treatment outcomes of PCa. Any treatment for PCa can have a long-lasting negative impact on quality of life and sexual health, which should be assessed by validated self-reported questionnaires. In particular, sexual health, urinary continence, and bowel function can be worsened after prostatectomy, radiotherapy, or hormone treatment, mostly in the elderly population. In the present review we summarized the current knowledge on the role of hormones, metabolic features, and primary treatments for PCa on the quality of life and sexual health of elderly Pca survivors.
    Full-text · Article · Mar 2014 · International Journal of Endocrinology
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    • "The study by van der Wielen et al18 found no correlation between ED at 2 years and dose to either the crura or the penile bulb in a study of 96 patients treated with doses of 68 to 78 Gy. However, Mangar et al19 reported a significant correlation at 2 years between the penile bulb dose-volume histogram (DVH) and ED in 51 men with baseline potency who had received 3 to 6 months of hormonal treatment and 64 or 74 Gy of radiotherapy. Dose received by 90% of the penile bulb (D90) > 50 Gy was significantly associated with ED (P = 0.006). "
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    ABSTRACT: This study sought to evaluate patient-reported health-related quality of life following proton therapy for prostate cancer in men ≤60 years old. Between August 2006 and January 2010, 262 hormone-naive men ≤60 years old were treated with definitive proton therapy for prostate cancer. Before treatment and every 6 months after treatment, patients filled out the Expanded Prostate Index Composite (EPIC) and the International Index of Erectile Function (IIEF) questionnaires. Potency was defined as successful sexual intercourse in the prior month or an EPIC sexual summary (SS) score ≥60. Median follow-up was 24 months; 90% of men completed follow-up EPIC forms within the last year. For EPIC urinary, bowel, and hormone subscales, the average decline from baseline to 2 years was ≤5 points, except for bowel function (5.2 points). SS scores declined 12.6 points after 2 years. Potency rates declined by 11% from baseline at 2 years, but 94% of men were potent with a baseline IIEF > 21, body mass index < 30, and no history of diabetes. At 2 years after treatment, only 1.8% of men required a pad for urge incontinence. On multivariate analysis, factors associated with a significant decline in SS score were mean penile bulb dose ≥40 cobalt Gy equivalents (P = .012) and radiation dose ≥80 cobalt Gy equivalents (P = .017); only diabetes was significantly associated with impotence (P = .015). Young men undergoing proton therapy for treatment of prostate cancer have excellent outcomes with respect to erectile dysfunction, urinary incontinence, and other health-related quality of life parameters during the first 2 years after treatment. Longer follow-up is needed to confirm these findings. Cancer 2012. © 2012 American Cancer Society.
    Full-text · Article · Sep 2012 · Cancer
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    • "In order to facilitate inter-patient comparisons, the maps were normalized in the longitudinal direction by interpolation to maps of 21×21 pixels. This was implemented using in-house software Guiness (Mangar et al. 2006). Each DSM was next described as a set of binary images. "
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    ABSTRACT: Many models exist for predicting toxicities based on dose-volume histograms (DVHs) or dose-surface histograms (DSHs). This approach has several drawbacks as firstly the reduction of the dose distribution to a histogram results in the loss of spatial information and secondly the bins of the histograms are highly correlated with each other. Furthermore, some of the complex nonlinear models proposed in the past lack a direct physical interpretation and the ability to predict probabilities rather than binary outcomes. We propose a parameterized representation of the 3D distribution of the dose to the rectal wall which explicitly includes geometrical information in the form of the eccentricity of the dose distribution as well as its lateral and longitudinal extent. We use a nonlinear kernel-based probabilistic model to predict late rectal toxicity based on the parameterized dose distribution and assessed its predictive power using data from the MRC RT01 trial (ISCTRN 47772397). The endpoints under consideration were rectal bleeding, loose stools, and a global toxicity score. We extract simple rules identifying 3D dose patterns related to a specifically low risk of complication. Normal tissue complication probability (NTCP) models based on parameterized representations of geometrical and volumetric measures resulted in areas under the curve (AUCs) of 0.66, 0.63 and 0.67 for predicting rectal bleeding, loose stools and global toxicity, respectively. In comparison, NTCP models based on standard DVHs performed worse and resulted in AUCs of 0.59 for all three endpoints. In conclusion, we have presented low-dimensional, interpretable and nonlinear NTCP models based on the parameterized representation of the dose to the rectal wall. These models had a higher predictive power than models based on standard DVHs and their low dimensionality allowed for the identification of 3D dose patterns related to a low risk of complication.
    Full-text · Article · Mar 2011 · Physics in Medicine and Biology
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