Sexual Structure Sparing for Prostate Cancer Radiotherapy: A Systematic Review.

CONTEXT: Erectile dysfunction represents a major side effect of prostate cancer (PCa) treatment, negatively impacting men's quality of life. While radiation therapy (RT) advances have enabled the mitigation of both genitourinary and gastrointestinal toxicities, no significant improvement has been showed in sexual quality of life over time. OBJECTIVE: The primary aim of this review was to assess sexual structures' dose-volume parameters associated with the onset of erectile dysfunction. EVIDENCE ACQUISITION: We searched the PubMed database and ClinicalTrials.gov until January 4, 2023. Studies reporting the impact of the dose delivered to sexual structures on sexual function or the feasibility of innovative sexual structure-sparing approaches were deemed eligible. EVIDENCE SYNTHESIS: Sexual-sparing strategies have involved four sexual organs. The mean penile bulb doses exceeding 20 Gy are predictive of erectile dysfunction in modern PCa RT trial. Maintaining a D100% of ≤36 Gy on the internal pudendal arteries showed preservation of erectile function in 88% of patients at 5 yr. Neurovascular bundle sparing appears feasible with magnetic resonance-guided radiation therapy, yet its clinical impact remains unanswered. Doses delivered to the testicles during PCa RT usually remain <2 Gy and generate a decrease in testosterone levels ranging from -4.6% to -17%, unlikely to have any clinical impact. CONCLUSIONS: Current data highlight the technical feasibility of sexual sparing for PCa RT. The proportion of erectile dysfunction attributable to the dose delivered to sexual structures is still largely unknown. While the ability to maintain sexual function over time is impacted by factors such as age or comorbidities, only selected patients are likely to benefit from sexual-sparing RT. PATIENT SUMMARY: Technical advances in radiation therapy (RT) made it possible to significantly lower the dose delivered to sexual structures. While sexual function is known to decline with age, the preservation of sexual structures for prostate cancer RT is likely to be beneficial only in selected patients.

Assessing Inter-Fraction Changes in The Size and Position of The Penile Bulb During Daily MR-Guided Radiation Therapy to The Prostate Bed: Do We Need to Adjust How We Plan Radiation in The Post-Radical Prostatectomy Setting to Reduce Risk of Erectile Dysfunction?

BACKGROUND: We evaluated inter-fraction penile bulb (PB) changes in prostate cancer (PCa) patients undergoing MR-guided RT in the post-radical prostatectomy (RP) setting. MATERIALS AND METHODS: 10 patients with PCa status-post RP received MR-guided RT from 2017-2019. Patients received daily setup volumetric MRI scans prior to RT delivery for alignment and target localization. Setup MRI datasets from Fx 1, Fx 19, and Fx 37 were fused for each patient based on soft tissue anatomy. The PB was contoured on each MRI. Data on volume (cc), superior/inferior positional change (cm), and mean dose (Gy) was collected. Differences were assessed by Student's t-test (sig. p<0.05). RESULTS: The mean PB volume change from Fx 1→ 19 was +0.34 ± 0.34 cc (p=0.11) and from Fx 1→ 37 was +0.22 ± 0.28 cc (p=0.31). The mean positional change from Fx 1→ 19 was +0.08±0.26 cm (p=0.37) and from Fx 1→ 37 was +0.05 ±0.25 cm (p=0.57). The mean change in mean PB dose from Fx 1→ 19 was +0.19±4.86 Gy (p=0.98) and from Fx 1→ 37 was -1.51≖7.46 Gy (p=0.88). CONCLUSION: We present the first study evaluating inter-fraction changes to the PB during MR-guided RT. We found no clinically meaningful difference in the volume, positional change, or mean dose during RT in the post-prostatectomy setting, suggesting that PB organ motion may not need to be accounted for in radiation treatment planning.

Interrater agreement of contouring of the neurovascular bundles and internal pudendal arteries in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.

BACKGROUND AND PURPOSE: Radiation damage to neural and vascular tissue, such as the neurovascular bundles (NVBs) and internal pudendal arteries (IPAs), during radiotherapy for prostate cancer (PCa) may cause erectile dysfunction. Neurovascular-sparing magnetic resonance-guided adaptive radiotherapy (MRgRT) aims to preserve erectile function after treatment. However, the NVBs and IPAs are not routinely contoured in current radiotherapy practice. Before neurovascular-sparing MRgRT for PCa can be implemented, the interrater agreement of the contouring of the NVBs and IPAs on pre-treatment MRI needs to be assessed. MATERIALS AND METHODS: Four radiation oncologists independently contoured the prostate, NVB, and IPA in an unselected consecutive series of 15 PCa patients, on pre-treatment MRI. Dice similarity coefficients (DSCs) for pairwise interrater agreement of contours were calculated. Additionally, the DCS of a subset of the inferior half of the NVB contours (i.e. approximately prostate midgland to apex level) was calculated. RESULTS: Median overall interrater DSC for the left and right NVB was 0.60 (IQR: 0.54 - 0.68) and 0.61 (IQR: 0.53 - 0.69) respectively and for the left and right IPA 0.59 (IQR: 0.53 - 0.64) and 0.59 (IQR: 0.52 - 0.64) respectively. Median overall interrater DSC for the inferior half of the left NVB was 0.67 (IQR: 0.58 - 0.74) and 0.67 (IQR: 0.61 - 0.71) for the right NVB. CONCLUSION: We found that the interrater agreement for the contouring of the NVB and IPA improved with enhancement of the MRI sequence as well as further training of the raters. The agreement was best in the subset of the inferior half of the NVB, where a good agreement is clinically most relevant for neurovascular-sparing MRgRT for PCa.

Evaluation of erectile potency and radiation dose to the penile bulb using image guided radiotherapy in the CHHiP trial.

BACKGROUND AND PURPOSE: The penile bulb (PB) dose may be critical in development of post prostate radiotherapy erectile dysfunction (ED). This study aimed to generate PB dose constraints based on dose-volume histograms (DVHs) in patients treated with prostate radiotherapy, and to identify clinical and dosimetric parameters that predict the risk of ED post prostate radiotherapy. MATERIALS AND METHODS: Penile bulb DVHs were generated for 276 patients treated within the randomised IGRT substudy of the multicentre randomised trial, CHHiP. Incidence of ED in relation to dose and randomised IGRT groups were evaluated using Wilcoxon rank sum, Chi-squared test and atlases of complication incidence. Youden index was used to find dose-volume constraints that discriminated for ED. Multivariate analysis (MVA) of effect of dosimetry, clinical and patient-related variables was performed. RESULTS: Reduced treatment margins using IGRT (IGRT-R) produced significantly reduced mean PB dose compared with standard margins (IGRT-S) (median: 25 Gy (IGRT-S) versus 11 Gy (IGRT-R); p < 0.0001). Significant difference in both mean (median: 23 Gy (ED) vs. 18 Gy (no ED); p = 0.011) and maximum (median: 59 Gy (ED) vs. 52 Gy (no ED); p = 0.018) PB doses between those with and without clinician reported ED were identified. Mean PB dose cut-point for ED was derived at around 20 Gy. On MVA, PB mean dose and age predicted for impotence. CONCLUSION: PB dose appears predictive of post-radiotherapy ED with calculated threshold mean dose of around 20 Gy, substantially lower than published recommendations. IGRT-R enables favourable PB dosimetry and can be recommended provided prostate coverage is not compromised.

Erectile dysfunction in prostate cancer patients treated with intensity-modulated radiation therapy.

BACKGROUND: Sexual dysfunction is an important side-effect after radiotherapy (RT) for prostate cancer (PCa). The aim of this study was to compare sexual functions of PCa patients before and after intensity-modulated RT and to analyze their correlation with penile bulb (PB) doses and patient characteristics. MATERIALS AND METHODS: Forty-two patients who underwent RT ± hormone therapy for PCa between 2010 and 2013 were analyzed. Sexual functions assessed by patient-reported questionnaire and physician reported scale before and 3 years after treatment. The effect of patients' age, prostate volume, testosterone levels, comorbidity, smoking status, tumor stage, RT technique, hormone therapy, and PB doses to sexual functions were investigated. RESULTS: After 3 years of RT, 64.3% of all patients had a lower erectile score; and 75% of patients who were previously potent (n = 24) had become impotent after treatment. However sexual desire still remained in 75.8% of patients who had desire before treatment (n = 33). Statistical analysis showed that two parameters were correlated with postradiotherapy impotency outcome; PB mean radiation dose (P = 0.033) and testosterone levels (P = 0.032). CONCLUSIONS: RT, despite modern techniques, affects the sexual function of PCa patients in varying degrees. Reducing radiation doses to penile structures may play a role in preventing erectile dysfunction.

The Utility of Penile Bulb Contouring to Localise the Prostate Apex as Compared to Urethrography.

PURPOSE: High-precision radiotherapy relies on accurate anatomic localisation. Urethrography is often used to localise the prostatic apex. However, urethrography is an invasive localisation procedure and may introduce a systemic error. The penile bulb (PB) is contoured to minimise the risk of erectile dysfunction. The purpose of this study is to assess the value of using the PB, as an alternative to urethrography, to localise the prostate. METHODS AND MATERIALS: The PB was localised on 10 patients treated with simplified intensity-modulated arc radiotherapy at computed tomography simulation during treatment weeks 1 and 7. All patients underwent placement of fiducial markers. Urethrography was used only at simulation. Distances from the superior PB contour to the inferior prostate contour, the apex fiducial marker, and to the inferior prostate contour were obtained as well. The PB was contoured by two observers independently. Agreement coefficients and analysis of variance were used to assess reliability between rates and consistency of measurements over time. RESULTS: The PB-apex distance was greater than or equal to the urethrogram-apex distance in 24/30 (80%) measurements, and the median difference was 3 mm and was consistent between raters. The greatest variation in PB-IM distance between weeks was 6 mm, the median was 3 mm, and the agreements of measurements between weeks for raters 1 and 2 were 0.79 and 0.69, respectively. These differences were not statistically different and were consistent with the computed tomography slice thickness. CONCLUSIONS: The PB can be used to identify the prostate apex and can be reliably contoured between observers. Measurements are consistent between patients and through the duration of treatment. The PB distance measurements support studies indicating that urethrography causes a shift of the prostate superiorly. The distance from the PB to prostate apex remains stable during treatment for individual patients but varies between patients.