Bladder exstrophy-epispadias complex: The effect of urotherapy on incontinence.

INTRODUCTION: Achieving urinary continence is a key goal in children born with the bladder exstrophy-epispadias complex (BEEC). Unfortunately, this goal is only moderately achieved despite sometimes extensive surgical treatment. Undergoing repeated hospitalization and operations may consequently have a negative impact on quality of life. We therefore believe that other, conservative treatment options should be explored in an earlier stage of incontinence treatment in BEEC patients. As part of this, an intensive urotherapy program based on was offered to patients with persistent incontinence after reconstructive surgery for BEEC. OBJECTIVE: The aim of this study is to evaluate the benefits of intensive urotherapy on incontinence after reconstructive surgery in children with BEEC. STUDY DESIGN: A retrospective chart study was performed including all children who were enrolled in an intensive urotherapy program because of persistent incontinence after reconstructive surgery for BEEC. Urotherapy consisted of a ten-day inpatient training program based on cognitive behavioral therapy, with intensive follow-up by experienced urotherapists. Main outcome measurement was continence, expressed as the percentage of children that achieved complete continence (good result; 100% dry) or 50-99% decrease of wet days a week (improved result) after treatment. RESULTS: Data of 33 patients with a mean age of 10.6 years were analyzed. In 61% of cases (20/33) an improved or good result was reported on incontinence after urotherapy. Children with classic bladder exstrophy more often achieved a good or improved result (13/16; 81%), compared to children with epispadias (6/16; 38%). The only patient with a cloacal exstrophy completed treatment with an improved result. From the group of patients with persistent incontinence, 75% (12/16) reported that the complaints were socially acceptable at the end of follow-up. DISCUSSION: By following our intensive urotherapy program the majority of patients achieved complete continence or improved incontinence. In addition, our results show that the inpatient training program has a positive impact on acceptance in cases of persistent incontinence. The urotherapists offer individualized care and clear guidance, which we deem essential elements of successful treatment. Considering that repeated surgery may impede progress and offers no guarantee of continence, we recommend giving preference to conservative treatment options. CONCLUSION: Our results show that 37% (12/33) of patients with BEEC who were enrolled in our intensive urotherapy program because of persistent incontinence after reconstructive surgery, achieved complete continence after urotherapy and 63% (21/33) still experienced some degree of incontinence. 75% of patients who did not achieve complete continence, described the remaining incontinence as socially acceptable. These findings strongly support counselling patients with BEEC to consider conservative treatment before opting for further surgery.

Daily online contouring and re-planning versus translation-only correction in neurovascular-sparing magnetic resonance-guided radiotherapy for localized prostate cancer.

Neurovascular bundle (NVB) and internal pudendal artery (IPA) sparing during magnetic resonance-guided radiotherapy (MRgRT) for prostate cancer aims for preservation of erectile function. Our present workflow involves daily online contouring and re-planning on a 1.5 T MR-linac, as alternative to conventional (rigid) translation-only corrections of the prostate. We compared planned dose for the NVB and IPA between strategies. Total planned dose was significantly lower with daily online contouring and re-planning for the NVB, but not for the IPA. For the NVB and IPA, the intrapatient difference between highest and lowest fraction dose was significantly smaller for the contouring and re-planning plans.

Neurovascular-Sparing MR-Guided Adaptive Radiotherapy in Prostate Cancer; Defining the Potential Population for Erectile Function-Sparing Treatment.

BACKGROUND: Magnetic resonance-guided adaptive radiotherapy (MRgRT) enables neurovascular-sparing treatment for localized prostate cancer (PCa). The aim of this treatment is preservation of erectile function by sparing the neurovascular bundles, the internal pudendal arteries, the corpora cavernosa, and the penile bulb. Internal pudendal arteries, corpora cavernosa, and penile bulb sparing can generally be achieved in all patients, but NVB sparing can be challenging due to its proximity to the prostate and is therefore dependent on tumor location. PCa patients that have sufficient erectile function at baseline and favorable tumor characteristics might benefit from this treatment. Currently, it is unclear what proportion of patients are eligible for neurovascular-sparing treatment and to what extent this is technically feasible. AIM: To define the eligibility and technical feasibility for neurovascular-sparing MRgRT in intermediate-risk localized PCa patients. METHODS: A consecutive series of men that received 5 × 7.25 gray (Gy) MRgRT for localized PCa were included. Baseline erectile function was assessed using the International Index of Erectile Function (IIEF)-5 questionnaire. Additionally, the ability of sparing the neurovascular bundles was assessed in all patients. Per neurovascular-sparing protocol, the dominant intraprostatic lesion with a 4 mm isotropic margin should receive 34.44 Gy in ≥ 99% of the volume (i.e., high-dose area). When the high-dose area directly borders or overlaps the NVB because of a dorsolateral position of the dominant intraprostatic lesion, sparing of the NVB was considered not feasible on that side. OUTCOMES: Patient-reported IIEF-5 baseline questionnaires and the technical feasibility of NVB sparing were assessed. RESULTS: Of the 102 men that completed the IIEF-5 questionnaire at baseline, 49.0% of patients reported to have an IIEF-5 score of ≥ 17. In those patients, the NVB could technically have been spared bilaterally in 20.0% and unilaterally in 68.0%. CLINICAL IMPLICATIONS: Our findings define the potential population for neurovascular-sparing MRgRT for localized PCa and indicate the proportion in which the NVB can technically be spared. STRENGTH & LIMITATIONS: The major strength of this study is the prospective collection of data. The limitations include that the neurovascular-sparing feasibility definition is based on pre-clinical planning data. CONCLUSION: A substantial group of 49.0% of patients in our study had mild or no erectile dysfunction at baseline. Of these patients, the NVB could technically have been spared bilaterally in 20.0% and unilaterally in 68.0% during MRgRT. Trials need to assess the effect of neurovascular-sparing MRgRT on erectile function. Teunissen FR, van der Voort van Zyp JRN, Verkooijen HM, et al., Neurovascular-Sparing MR-Guided Adaptive Radiotherapy in Prostate Cancer; Defining the Potential Population for Erectile Function-Sparing Treatment. J Sex Med 2022;19:1196-1200.

Adaptive magnetic resonance-guided neurovascular-sparing radiotherapy for preservation of erectile function in prostate cancer patients.

BACKGROUND AND PURPOSE: Erectile dysfunction is a common adverse effect of external beam radiation therapy for localized prostate cancer (PCa), likely as a result of damage to neural and vascular tissue. Magnetic resonance-guided online adaptive radiotherapy (MRgRT) enables high-resolution MR imaging and paves the way for neurovascular-sparing approaches, potentially lowering erectile dysfunction after radiotherapy for PCa. The aim of this study was to assess the planning feasibility of neurovascular-sparing MRgRT for localized PCa. MATERIALS AND METHODS: Twenty consecutive localized PCa patients, treated with standard 5×7.25 Gy MRgRT, were included. For these patients, neurovascular-sparing 5×7.25 Gy MRgRT plans were generated. Dose constraints for the neurovascular bundle (NVB), the internal pudendal artery (IPA), the corpus cavernosum (CC), and the penile bulb (PB) were established. Doses to regions of interest were compared between the neurovascular-sparing plans and the standard clinical pre-treatment plans. RESULTS: Neurovascular-sparing constraints for the CC, and PB were met in all 20 patients. For the IPA, constraints were met in 19 (95%) patients bilaterally and 1 (5%) patient unilaterally. Constraints for the NVB were met in 8 (40%) patients bilaterally, in 8 (40%) patients unilaterally, and were not met in 4 (20%) patients. NVB constraints were not met when gross tumor volume (GTV) was located dorsolaterally in the prostate. Dose to the NVB, IPA, and CC was significantly lower in the neurovascular-sparing plans. CONCLUSIONS: Neurovascular-sparing MRgRT for localized PCa is feasible in the planning setting. The extent of NVB sparing largely depends on the patient's GTV location in relation to the NVB.

Hyprofractionated Versus Conventionally Fractionated Radiation Therapy for Patients with Intermediate- or High-Risk, Localized, Prostate Cancer: 7-Year Outcomes From the Randomized, Multicenter, Open-Label, Phase 3 HYPRO Trial.

PURPOSE: In the multicenter, phase 3, HYpofractionated irradiation for PROstate cancer trial, hypofractionated (HF) radiation therapy was compared with conventionally fractionated (CF) radiation therapy. In previous reports, we could not demonstrate the postulated superiority of hypofractionation in terms of relapse-free survival at 5 years. The frequent use of long-term androgen deprivation therapy might have had substantial effects on relapse-free survival. In the current analysis, we provide updated 7-year relapse-free survival outcomes. METHODS AND MATERIALS: We enrolled patients with intermediate- to high-risk T1b-T4NX-N0MX-M0 localized prostate cancer. Patients were randomly assigned (1:1) to either HF (64.6 Gy in 19 fractions) or CF (78.0 Gy in 39 fractions) radiation therapy. Based on an estimated α/ß ratio for prostate cancer of 1.5 Gy, the EQD2 was 90.4 Gy for HF versus 78.0 Gy for CF radiation therapy. The primary endpoint of the present analysis is relapse-free survival at 7 years. RESULTS: A total of 820 patients were enrolled, of whom 804 were assessable for the current evaluation (407 HF versus 397 CF). Median follow-up was 89 months (interquartile range, 83-99). Concomitant androgen deprivation therapy was prescribed for 537 (67%) of 804 patients for a median duration of 32 months (interquartile range, 10-44). Treatment failure at 7 years was reported in 220 (27.4%) of 804 patients, 107 (26.3%) in HF versus 113 (28.5%) in CF radiation therapy. Seven-year relapse-free survival was 71.7% (95% confidence interval [CI], 66.4-76.4) for HF versus 67.6% (95% CI, 62.0-72.5) for CF (P = .52). Overall survival was 80.8% (95% CI, 76.5-84.4) in HF versus 77.6% (95% CI, 73.0-81.5) in CF radiation therapy (P = .17). CONCLUSIONS: The current results of 7-year relapse-free survival confirmed our previous findings that the hypothesized dose escalation in the HF arm did not translate to superior tumor control compared with the CF arm.

Sexual Function in Patients Treated With Stereotactic Radiotherapy For Prostate Cancer: A Systematic Review of the Current Evidence.

INTRODUCTION: Sexual function can be impaired by all prostate cancer treatment modalities, but studies specifically addressing the impact of stereotactic body radiotherapy (SBRT) on sexual function are scarce. AIM: To systematically evaluate sexual outcomes in patients treated by SBRT for prostate cancer and determine clinical factors associated with erectile dysfunction (ED). METHODS: A systematic review of the available literature was performed on PubMed/Medline, Scopus, and Cochrane Library databases in June 2017 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Only articles providing data on baseline and post-treatment sexual function after SBRT (≥5 Gy/fraction) were included in this analysis (n = 12). MAIN OUTCOME MEASURE: Sexual function deteriorates after SBRT of the prostate. RESULTS: Deterioration of sexual health was found, with Expanded Prostate Cancer Index Composite-26 sexual domain scores showing a median decrease of 9.2 at 12 months and a median decrease of the Sexual Health Inventory for Men subdomain score by 2.7 at 12 months (from baseline median value of 56.3 and 16, respectively). At 60 months, ED was reported by 26-55% of previously sexually functioning patients in 5 of the 12 studies. CLINICAL IMPLICATIONS: ED affects ≤55% of previously sexually functioning patients at 5 years, as reported for other non-surgical treatment modalities. STRENGTHS & LIMITATIONS: This study enforced strict inclusion criteria of selected studies and exclusion of patients receiving concurrent androgen deprivation therapy. However, inconsistencies in the choice of assessment tool and definition of ED hamper a robust meta-analysis of pooled data. CONCLUSION: Sexual function decline after SBRT for prostate cancer appears to be similar to other modalities and should be specifically addressed in future studies. Loi M, Wortel RC, Francolini G, et al. Sexual Function in Patients Treated With Stereotactic Radiotherapy For Prostate Cancer: A Systematic Review of the Current Evidence. J Sex Med 2019;16:1409-1420.

Moderate Hypofractionation in Intermediate- and High-Risk, Localized Prostate Cancer: Health-Related Quality of Life From the Randomized, Phase 3 HYPRO Trial.

PURPOSE: The phase 3 Hypofractionated Irradiation for Prostate Cancer trial compared hypofractionated radiation therapy with conventionally fractionated radiation therapy in patients with localized prostate cancer. Similar 5-year relapse-free survival rates were achieved in both groups, but noninferiority of hypofractionation was not confirmed for genitourinary and gastrointestinal toxicity. Here, we present the secondary trial endpoint on patient-reported quality of life. METHODS AND MATERIALS: A total of 820 patients with intermediate-risk or high-risk prostate cancer were randomized to hypofractionation (19 fractions of 3.4 Gy) or conventional fractionation (39 fractions of 2.0 Gy). Quality of life was measured using a validated questionnaire, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer 25 module. Subscales (score range, 0-100) on urinary symptoms, gastrointestinal symptoms, symptoms related to androgen deprivation therapy, sexual function, and sexual activity were analyzed. Changes from baseline of at least 5 points were considered clinically relevant. Inferiority of hypofractionation for separate subscales was rejected if the mean difference in the 3-year incidence of clinically relevant deterioration between treatments was <8.0%. RESULTS: A total of 697 men were eligible for this quality-of-life analysis. Baseline characteristics were comparable between both groups. At 3-year follow-up, the incidence of clinically relevant deterioration of urinary symptoms was 33% for both treatments (difference 0.49% in favor of conventional fractionation; 90% confidence interval, -7.20% to 8.18%). Such deterioration of gastrointestinal symptoms was reported in 38% of patients receiving hypofractionation versus 36% of patients receiving conventional fractionation (2.03% in favor of conventional fractionation; 90% confidence interval, -6.18% to 10.23%). Therefore, we could not demonstrate noninferiority of hypofractionation for genitourinary and gastrointestinal quality of life. For all other subscales, noninferiority of hypofractionation was demonstrated. CONCLUSIONS: Noninferiority of the hypofractionated treatment was not demonstrated for genitourinary and gastrointestinal quality of life, and therefore we cannot rule out that relevant differences may exist between both treatments. Noninferiority of hypofractionation was demonstrated for symptoms related to androgen deprivation therapy, sexual activity, and sexual function.

Reporting Erectile Function Outcomes After Radiation Therapy for Prostate Cancer: Challenges in Data Interpretation.

BACKGROUND: Choice of prostate cancer treatment is frequently influenced by the expected chance of treatment-induced side effects such as erectile dysfunction (ED). However, great discrepancy in cited ED rates exists in the contemporary radiation therapy literature. AIM: To analyze the reported ED rates and cause of discrepancies and explore the strengths and limitations in the literature on radiation-induced ED. METHODS: We performed a PubMed literature search and reviewed the literature on ED rates associated with external-beam radiotherapy and brachytherapy from the past 10 years. Eighteen studies were eligible for inclusion and subsequently reviewed. OUTCOMES: Variables required for interpretation of erectile function outcomes, including patient demographics, treatment characteristics, and sexual function outcomes. RESULTS: A large variety in the reported incidence of ED was found among studies. In part, these differences resulted from large variations in (i) study populations, (ii) patient characteristics, (iii) treatment characteristics, (iv) prescription of androgen deprivation therapy, (v) means of data acquisition, (vi) definitions of ED, (vii) temporal considerations, and (viii) erectile aid use. Relevant data required for adequate appraisal of sexual function outcomes were not always reported. CLINICAL IMPLICATIONS: Based on the present findings, we present general recommendations for reporting of erectile function outcomes after radiotherapy for prostate cancer. These should improve future reports. STRENGTHS AND LIMITATIONS: This is the first report that presents general requirements on reporting erectile function outcomes in the setting of radiotherapy for prostate cancer. We did not conduct a formal meta-analysis because we focused on concepts of research design; this might be considered a limitation. CONCLUSION: In this review, we have highlighted the strengths and deficiencies of the current literature on ED after external-beam radiotherapy and brachytherapy for prostate cancer. We have made general recommendations to achieve some degree of standardization among reports and improve clinical interpretability. Wortel RC, Incrocci L, Muhall JP. Reporting Erectile Function Outcomes After Radiation Therapy for Prostate Cancer: Challenges in Data Interpretation. J Sex Med 2017;14:1260-1269.

Local Protocol Variations for Image Guided Radiation Therapy in the Multicenter Dutch Hypofractionation (HYPRO) Trial: Impact of Rectal Balloon and MRI Delineation on Anorectal Dose and Gastrointestinal Toxicity Levels.

PURPOSE: The phase 3 HYpofractionated irradiation for PROstate cancer (HYPRO) trial randomized patients with intermediate- to high-risk localized prostate cancer to conventionally fractionated (78 Gy in 39 fractions) or hypofractionated (64.6 Gy in 19 fractions) radiation therapy. Differences in techniques and treatment protocols were present between participating centers. This study aimed to compare dose parameters and patient-reported gastrointestinal symptoms between these centers. METHODS AND MATERIALS: From the trial population, we selected patients (N=572) from 4 treatment centers who received image guided (IG) intensity modulated radiation therapy (IMRT). Center A (n=242) applied planning target volume (PTV) margins of 5 to 6 mm and was considered the reference center. In center B (n=170, 7-mm margins), magnetic resonance imaging (MRI) was integrated in treatment planning. An endorectal balloon (ERB) was applied in center C (n=85, 7-mm margins). Center D (n=75) applied the largest PTV margins of 8 mm. The study protocol provided identical anorectal dose constraints, and local protocols were applied for further treatment optimization. Anorectal dose-surface histograms were compared by applying t tests. Rectal complaints during follow-up (6 months to 4 years) were compared in a generalized linear model, adjusting for age, follow-up, treatment arm, and hormone therapy. RESULTS: Favorable anorectal dose distributions were found for center B (MRI delineation) and center C (ERB application) as compared with centers A and D. These were associated with significantly lower incidences of patient-reported complaints of rectal incontinence, use of incontinence pads, and rectal discomfort in these centers. Furthermore, lower incidences of increased stool frequency (≥4 per day) and mucous loss were observed for center C. CONCLUSIONS: Despite comparable IG-IMRT techniques and predefined dose constraints, pronounced differences in dose distributions and toxicity rates were observed. MRI delineation and ERB application were associated with favorable rectal dose parameters and toxicity profiles, whereas a 2- to 3-mm difference in PTV margins did not translate into observed differences. We conclude that choices for treatment optimization of IG-IMRT are important and clinically relevant for patients since these affect symptoms experienced in daily life.

Sexual Function After Hypofractionated Versus Conventionally Fractionated Radiotherapy for Prostate Cancer: Results From the Randomized Phase III HYPRO Trial.

INTRODUCTION: Hypofractionated radiotherapy could increase the radiobiological tumor dose for localized prostate cancer. The effects of hypofractionation on sexual function are not well known. AIM: To compare sexual function in patients with prostate cancer treated with 78 Gy in 39 fractions of 2 Gy or 64.6 Gy in 19 fractions of 3.4 Gy. METHODS: In total, 820 men with intermediate- to high-risk T1b-T4NX-0MX-0 prostate cancer were enrolled in the phase III HYPRO trial (2007-2010) and randomized to conventional fractionation (39 × 2 Gy) or hypofractionation (19 × 3.4 Gy). Sexual function was assessed at baseline and at 6, 12, 24, and 36 months after treatment using the International Index of Erectile Function (IIEF). For this analysis, patients (n = 322) with a baseline assessment, at least one follow-up assessment, and no or short-term (6-month) androgen-deprivation therapy were included. MAIN OUTCOME MEASURES: Mean IIEF domain scores were compared between treatments in the total population and the hormone-naïve population (n = 197) using the independent t-test. Incidences of severe erectile dysfunction (domain score < 11) at last follow-up were calculated in patients with partial or full baseline function. Binary logistic regression analyses were applied to calculate the odds ratio of hypofractionation vs conventional fractionation and to adjust for clinical factors. RESULTS: Median age was 71 years (interquartile range = 67-71) and median follow-up was 37 months (interquartile range = 25-38). Androgen-deprivation therapy was prescribed in 125 (39%). IIEF domain scores decreased after treatment but were comparable between treatment arms at baseline and during follow-up. Orgasmic function scores in hormone-naïve patients were significantly higher at 3 years after hypofractionation (4.08 vs 2.65, P = .031). In patients (n = 120) with partial or full baseline erectile function, the incidence of erectile dysfunction at last follow-up was 34.4% for hypofractionated treatment vs 39.3% for conventional treatment (adjusted odds ratio = 0.84, 95% CI = 0.37-1.90, P = .67). CONCLUSION: No significant differences in erectile functioning between conventional and hypofractionated radiotherapy were found. Hormone-naïve patients reported significantly higher orgasmic function scores at 3 years after hypofractionation.

Hypofractionated versus conventionally fractionated radiotherapy for patients with localised prostate cancer (HYPRO): final efficacy results from a randomised, multicentre, open-label, phase 3 trial.

BACKGROUND: Studies have reported a low α/ß ratio for prostate cancer, suggesting that hypofractionation could enhance the biological tumour dose without increasing genitourinary and gastrointestinal toxicity. In the multicentre phase 3, HYpofractionated irradiation for PROstate cancer (HYPRO) trial, hypofractionated radiotherapy was compared with conventionally fractionated radiotherapy for treatment of prostate cancer. We have previously reported acute and late incidence of genitourinary and gastrointestinal toxicity; here we report protocol-defined 5-year relapse-free survival outcomes. METHODS: We did an open-label, randomised, phase 3 trial at seven Dutch radiotherapy centres. We enrolled patients with intermediate-risk to high-risk T1b-T4NX-N0MX-M0 localised prostate cancer, a prostate-specific antigen concentration of 60 µg/L or less, and a WHO performance status of 0-2. We used a web-based application to randomly assign (1:1) patients to either hypofractionated radiotherapy of 64·6 Gy (19 fractions of 3·4 Gy, three fractions per week) or conventionally fractionated radiotherapy of 78·0 Gy (39 fractions of 2·0 Gy, five fractions per week). Based on an estimated α/ß ratio for prostate cancer of 1·5 Gy, the equivalent total dose in fractions of 2·0 Gy was 90·4 Gy for hypofractionation compared with 78·0 Gy for conventional fractionation. The primary endpoint was relapse-free survival. All analyses were done on an intention-to-treat basis in all eligible patients. The HYPRO trial completed recruitment in 2010 and follow-up is ongoing. This trial is registered with ISRCTN, number ISRCTN85138529. FINDINGS: Between March 19, 2007, and Dec 3, 2010, 820 patients were enrolled, of whom 804 were eligible and assessable for intention-to-treat analyses. Of these, 407 were assigned hypofractionated radiotherapy and 397 were allocated conventionally fractionated radiotherapy. 537 (67%) of 804 patients received concomitant androgen deprivation therapy for a median duration of 32 months (IQR 10-44). Median follow-up was 60 months (IQR 51-69). Treatment failure was reported in 169 (21%) of 804 patients, 80 (20%) in the hypofractionation group and 89 (22%) in the conventional fractionation group. 5-year relapse-free survival was 80·5% (95% CI 75·7-84·4) for patients assigned hypofractionation and 77·1% (71·9-81·5) for those allocated conventional fractionation (adjusted hazard radio 0·86, 95% CI 0·63-1·16; log-rank p=0·36). There were no treatment-related deaths. INTERPRETATION: Hypofractionated radiotherapy was not superior to conventional radiotherapy with respect to 5-year relapse-free survival. Our hypofractionated radiotherapy regimen cannot be regarded as the new standard of care for patients with intermediate-risk or high-risk prostate cancer. FUNDING: Dutch Cancer Society.

Late Side Effects After Image Guided Intensity Modulated Radiation Therapy Compared to 3D-Conformal Radiation Therapy for Prostate Cancer: Results From 2 Prospective Cohorts.

PURPOSE: Technical developments in the field of external beam radiation therapy (RT) enabled the clinical introduction of image guided intensity modulated radiation therapy (IG-IMRT), which improved target conformity and allowed reduction of safety margins. Whether this had an impact on late toxicity levels compared to previously applied three-dimensional conformal radiation therapy (3D-CRT) is currently unknown. We analyzed late side effects after treatment with IG-IMRT or 3D-CRT, evaluating 2 prospective cohorts of men treated for localized prostate cancer to investigate the hypothesized reductions in toxicity. METHODS AND MATERIALS: Patients treated with 3D-CRT (n=189) or IG-IMRT (n=242) to 78 Gy in 39 fractions were recruited from 2 Dutch randomized trials with identical toxicity scoring protocols. Late toxicity (>90 days after treatment) was derived from self-assessment questionnaires and case report forms, according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG-EORTC) scoring criteria. Grade ≥2 endpoints included gastrointestinal (GI) rectal bleeding, increased stool frequency, discomfort, rectal incontinence, proctitis, and genitourinary (GU) obstruction, increased urinary frequency, nocturia, urinary incontinence, and dysuria. The Cox proportional hazards regression model was used to compare grade ≥2 toxicities between both techniques, adjusting for other modifying factors. RESULTS: The 5-year cumulative incidence of grade ≥2 GI toxicity was 24.9% for IG-IMRT and 37.6% following 3D-CRT (adjusted hazard ratio [HR]: 0.59, P=.005), with significant reductions in proctitis (HR: 0.37, P=.047) and increased stool frequency (HR: 0.23, P<.001). GU grade ≥2 toxicity levels at 5 years were comparable with 46.2% and 36.4% following IG-IMRT and 3D-CRT, respectively (adjusted HR: 1.19, P=.33). Other strong predictors (P<.01) of grade ≥2 late toxicity were baseline complaints, acute toxicity, and age. CONCLUSIONS: Treatment with IG-IMRT reduced the risk of late grade ≥2 complications, whereas GU toxicities remained comparable. This clinically relevant observation demonstrates that IMRT and image-guidance should therefore be the preferred treatment option, provided that margin reduction is implemented with caution.

Dose-surface maps identifying local dose-effects for acute gastrointestinal toxicity after radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: We evaluated dose distributions in the anorectum and its relation to acute gastrointestinal toxicities using dose surface maps in an image-guided (IG) IMRT and 3D-conformal radiotherapy (3D-CRT) population. MATERIAL AND METHODS: For patients treated to 78 Gy with IG-IMRT (n=260) or 3D-CRT (n=215), for whom acute toxicity data were available, three types of surface maps were calculated: (1) total anorectum using regular intervals along a central axis with perpendicular slices, (2) the rectum next to the prostate, and (3) the anal canal (horizontal slicing). For each toxicity, an average dose map was calculated for patients with and without the toxicity and subsequently dose difference maps were constructed, 3D-CRT and IG-IMRT separately. P-values were based on permutation tests. RESULTS: Dose distributions in patients with grade ⩾2 acute proctitis were significantly different from dose distributions in patients without toxicity, for IG-IMRT and 3D-CRT. At the cranial and posterior rectal site, in areas receiving moderate dose levels (≈25-50 Gy), dose differences up to 10 Gy were identified for IG-IMRT. For pain, cramps, incontinence, diarrhea and mucus loss significant differences were found as well. CONCLUSIONS: We demonstrated significant relationships between acute rectal toxicity and local dose distributions. This may serve as a basis for subsequent dose-effect modeling in IG-IMRT, and improved dose constraints in current clinical practice.

Rare case of urinary tract infections and the "forgotten" solution.

This report presents a rare case of recurrent urinary tract infections in a kidney transplant patient. Analysis revealed a ureteral stump calculus 31 years after bilateral nephrectomy which was disintegrated by means of flexible ureteroscopy and holmium laser. In case of unexplained recurrent urinary tract infections and abdominal pain, urolithiasis in the ureteral stumps should be considered.

Acute toxicity after image-guided intensity modulated radiation therapy compared to 3D conformal radiation therapy in prostate cancer patients.

PURPOSE: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. METHODS AND MATERIALS: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. RESULTS: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). CONCLUSIONS: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.

Orchiectomy and radiotherapy for stage I-II testicular seminoma: a prospective evaluation of short-term effects on body image and sexual function.

INTRODUCTION: Orchiectomy followed by infradiaphragmatic radiotherapy is a common treatment for stage I-II testicular seminoma. Long-term effects of orchiectomy and radiotherapy for testicular seminomas on body image and sexual function have been reported; however, few data are available on short-term effects. Patients are usually of reproductive age and sexually active; therefore, short-term effects on body image and sexual function should also be studied. AIMS: To prospectively evaluate short-term effects of orchiectomy and radiotherapy on body image and sexual function in testicular seminoma patients. METHODS: Questionnaires on body image and sexual function were prospectively distributed to all testicular seminoma patients treated between 1999 and 2013. The questionnaire distributed prior to radiotherapy was returned by 161 patients; 133 (82%) returned the second after 3 months, and 120 (75%) completed the questionnaire after 6 months. MAIN OUTCOME MEASURES: Body image and sexual function as assessed by a Dutch questionnaire on body image and sexuality after radiotherapy and orchiectomy. RESULTS: Median age was 36 years (range 18-70). After orchiectomy, 48% expressed fertility concerns, and 61% reported their body had changed. Six months after treatment, erectile rigidity was significantly decreased compared with prior to radiotherapy (P = 0.016), and 23% reported decreased sexual interest, activity, and pleasure. Changes in body image were significantly associated with decreased sexual interest, pleasure, and erectile function. Even though 45% reported that treatment negatively affected their sexual life, the number of sexually active patients remained stable at 91%. [Correction added on 12 November 2014, after first online publication: 'prior radiotherapy' was corrected to 'prior to radiotherapy'.] CONCLUSIONS: Short-term effects of treatment included fertility concerns and changes in body image. Reported erectile rigidity was significantly decreased after 6 months, as were sexual interest, activity, and pleasure. Disease and treatment had negative effects on sexual life, and changes in body image were associated with sexual dysfunction. Therefore, body image and sexual functioning should be addressed at an early stage in order to offer adequate treatment and counseling.