Health-related quality of life after ultrafocal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer: reporting the patient's perspective

Purpose: For patients with a localized prostate cancer recurrence after radiotherapy, focal salvage treatment offers a less toxic alternative to whole-gland treatments, with the potential of preserving health-related quality of life (HR-QoL). With a focus on the patient's perspective of treatment, this study aims to describe HR-QoL after ultrafocal salvage high-dose-rate brachytherapy (HDR-BT), and to explore predictive factors affecting HR-QoL. Material and methods: We included 100 patients treated with ultrafocal salvage HDR-BT. Prostate cancer-related HR-QoL was assessed by the EORTC QLQ-PR25 questionnaire. Domains were urinary symptoms, bowel symptoms and sexual activity/functioning. For each domain, a mixed effects model was made to estimate HR-QoL trends over time. For domains showing clinically relevant change (≥10 points difference), the mixed effects model was used to explore potential predictors (age, baseline HR-QoL score, T-stage, tumor location, CTV size, dose to organs at risk and history of ADT). Results: Median follow-up was 20 months (IQR 13–30). Mean questionnaire response rate was 86% (range 72–100%). Median baseline scores were 12 (urinary), 0 (bowel) and 67/50 (sexual activity/functioning). Urinary symptoms and sexual functioning showed clinically relevant deterioration over time (maximum difference of 11 and 12 points, respectively). Worse baseline score and higher administered dose to the urethra (≥16 Gy) were predictive of increased urinary symptoms (p < 0.01 and p = 0.03). Better baseline score was predictive of better sexual functioning (p < 0.01). Conclusion: Ultrafocal salvage HDR-BT has negligible impact on bowel symptoms but does affect urinary symptoms and sexual functioning. Lower impact is predicted for patients with favorable urinary and sexual function at baseline. Urethral dose constraints should be closely monitored

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

Early health economic analysis of 1.5 T MRI-guided radiotherapy for localized prostate cancer: Decision analytic modelling

Background and purpose 1.5 Tesla magnetic resonance imaging radiotherapy linear accelerator (MR-Linac) is gaining interest for treatment of localized prostate cancer. Clinical evidence is lacking and it therefore remains uncertain whether MR-Linac is cost-effective. An early health economic analysis was performed to calculate the necessary relative reduction in complications and the maximum price of MR-Linac (5 fractions) to be cost-effective compared to 5, 20 and 39 fractionation schedules of external beam radiotherapy (EBRT) and low-dose-rate (LDR) brachytherapy. Materials and methods A state transition model was developed for men with localized prostate cancer. Complication rates such as grade ≥2 urinary, grade ≥2 bowel and sexual complications, and utilities were based on systematic literature searches. Costs were estimated from a Dutch healthcare perspective. Threshold analyses were performed to identify the thresholds of complications and costs for MR-Linac to be cost-effective, while holding other outcomes such as biochemical progression and mortality constant. One-way sensitivity analyses were performed to outline uncertainty outcomes. Results At €6460 per patient, no reductions in complications were needed to consider MR-Linac cost-effective compared to EBRT 20 and 39 fractions. Compared to EBRT 5 fractions and LDR brachytherapy, MR-Linac was found to be cost-effective when complications are relatively reduced by 54% and 66% respectively. Results are highly sensitive to the utilities of urinary, bowel and sexual complications and the probability of biochemical progression. Conclusions MR-Linac is found to be cost-effective compared to 20 and 39 fractions EBRT at baseline. For MR-Linac to become cost-effective over 5 fractions EBRT and LDR brachytherapy, it has to reduce complications substantially or be offered at lower costs

Determining the safety of ultrafocal salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer: A toxicity assessment of 150 patients

Background and purpose: Local re-treatment of radiorecurrent prostate cancer is potentially curative. However, the increased risk of severe toxicity may outweigh the opportunity of cancer control. This study aims to evaluate treatment-related toxicity from ultrafocal salvage high-dose-rate brachytherapy (HDR-BT) and to investigate potential risk factors. Materials and methods: Toxicity data from 150 treated patients (July 2013-November 2019) was collected from a prospective registry. The treatment aim was to deliver a single dose of 19 Gy to the recurrent lesion as identified on multiparametric MRI and PET-CT. Treating physicians graded genitourinary (GU) and gastro-intestinal (GI) toxicity and erectile dysfunction (ED) using the Common Terminology Criteria for Adverse Events (CTCAE) 4.0, at baseline and during follow-up. Domains with substantial (≥10%) new-onset grade ≥ 2 toxicity were further evaluated using mixed effects logistic regression to find potential risk factors. Results: Median follow-up time was 20 months (IQR 12-31). Over time, new-onset grade 2 and 3 toxicity was recorded in 41% and 3% (GU), 5% and 0% (GI) and 22% and 15% (ED). While GI toxicity remained stably low, grade ≥ 2 GU toxicity and ED were seen twice as frequent in the late phase (>3 months after treatment). Significant risk factors for grade ≥ 2 toxicity were baseline GU toxicity (grade ≥ 2), baseline ED (grade ≥ 2), IPSS (cut-off ≥ 14) and urethral dose (D10%, cut-off ≥ 17 Gy). Conclusion: Ultrafocal salvage HDR-BT is a safe re-treatment option, especially in patients with a favorable symptom profile at baseline. Adherence to urethral dose constraints is important to avoid GU toxicity

Focal salvage treatment for radiorecurrent prostate cancer: A magnetic resonance-guided stereotactic body radiotherapy versus high-dose-rate brachytherapy planning study

Background and Purpose: Magnetic resonance imaging (MRI)-guided focal salvage high-dose-rate brachytherapy (FS-HDR-BT) is one of the treatment options for radiorecurrent localized prostate cancer. However, due to the invasive nature of the treatment, not all patients are eligible. Magnetic resonance linear accelerator (MR-Linac) systems open up new treatment possibilities and could potentially replace FS-HDR-BT treatment. We conducted a planning study to investigate the feasibility of delivering a single 19 Gy dose to the recurrent lesion using a 1.5 Tesla MR-Linac system. Materials and Methods: Thirty patients who underwent FS-HDR-BT were included. The clinical target volume (CTV) encompassed the visible lesion plus a 5 mm margin. Treatment plans were created for a 1.5 Tesla MR-Linac system using a 1 mm planning target volume (PTV) margin. A dose of 19 Gy was prescribed to ≥ 95% of the PTV. In case this target could not be reached, i.e. when organs-at-risk (OAR) constraints were violated, a dose of ≥ 17 Gy to ≥ 90% of the PTV was accepted. MR-Linac plans were compared to clinical FS-HDR-BT plans. Results: Target dose coverage was achieved in 14/30 (47%) FS-HDR-BT plans and 17/30 (57%) MR-Linac plans, with comparable median D95% and D90%. In FS-HDR-BT plans, a larger volume reached ≥ 150% of the prescribed dose. Urethra D10%, rectum D1cm3, and rectum D2cm3 were lower in the FS-HDR-BT plans, while bladder dose was comparable for both modalities. Conclusion: Single fraction treatment of recurrent prostate cancer lesions may be feasible using stereotactic body radiotherapy (SBRT) on a MR-Linac system

Clinical implementation of MRI-based organs-at-risk auto-segmentation with convolutional networks for prostate radiotherapy.

BACKGROUND: Structure delineation is a necessary, yet time-consuming manual procedure in radiotherapy. Recently, convolutional neural networks have been proposed to speed-up and automatise this procedure, obtaining promising results. With the advent of magnetic resonance imaging (MRI)-guided radiotherapy, MR-based segmentation is becoming increasingly relevant. However, the majority of the studies investigated automatic contouring based on computed tomography (CT). PURPOSE: In this study, we investigate the feasibility of clinical use of deep learning-based automatic OARs delineation on MRI. MATERIALS AND METHODS: We included 150 patients diagnosed with prostate cancer who underwent MR-only radiotherapy. A three-dimensional (3D) T1-weighted dual spoiled gradient-recalled echo sequence was acquired with 3T MRI for the generation of the synthetic-CT. The first 48 patients were included in a feasibility study training two 3D convolutional networks called DeepMedic and dense V-net (dV-net) to segment bladder, rectum and femurs. A research version of an atlas-based software was considered for comparison. Dice similarity coefficient, 95% Hausdorff distances (HD95), and mean distances were calculated against clinical delineations. For eight patients, an expert RTT scored the quality of the contouring for all the three methods. A choice among the three approaches was made, and the chosen approach was retrained on 97 patients and implemented for automatic use in the clinical workflow. For the successive 53 patients, Dice, HD95 and mean distances were calculated against the clinically used delineations. RESULTS: DeepMedic, dV-net and the atlas-based software generated contours in 60 s, 4 s and 10-15 min, respectively. Performances were higher for both the networks compared to the atlas-based software. The qualitative analysis demonstrated that delineation from DeepMedic required fewer adaptations, followed by dV-net and the atlas-based software. DeepMedic was clinically implemented. After retraining DeepMedic and testing on the successive patients, the performances slightly improved. CONCLUSION: High conformality for OARs delineation was achieved with two in-house trained networks, obtaining a significant speed-up of the delineation procedure. Comparison of different approaches has been performed leading to the succesful adoption of one of the neural networks, DeepMedic, in the clinical workflow. DeepMedic maintained in a clinical setting the accuracy obtained in the feasibility study

Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer

Purpose : Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. Material and methods : Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI)-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT). Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE) version 4.0. Results : With a median follow-up of 12 months (range, 6-15), there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV) was 4.8 cc (range, 1.9-6.6 cc). A median of 8 catheters (range, 6-9) were used, and the median dose to the treatment volume (GTV) was a D95: 19.3 Gy (SD 15.5-19.4 Gy). Conclusions : Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients

Patient preferences for treatment modalities for localised prostate cancer

OBJECTIVES: To assess the patient preferences and utility scores for the different conventional and innovative treatment modalities for localised prostate cancer (PCa). SUBJECTS AND METHODS: Patients treated for localised PCa and healthy volunteers were invited to fill out a treatment-outcome scenario questionnaire. Participants ranked six different treatments for localised PCa from most to least favourable, prior to information. In a next step, treatment procedures, toxicity, risk of biochemical recurrence and follow-up regimen were comprehensibly described for each of the six treatments (i.e. treatment-outcome scenarios), after which patients re-ranked the six treatments. Additionally, participants gave a visual analogue scale (VAS) and time trade-off (TTO) score for each scenario. Differences between utility scores were tested by Friedman tests with post hoc Wilcoxon signed-rank tests. RESULTS: Eighty patients and twenty-nine healthy volunteers were included in the study. Before receiving treatment-outcome scenario information, participants ranked magnetic resonance-guided adaptive radiotherapy most often as their first choice (35%). After treatment information was received, active surveillance was most often ranked as the first choice (41%). Utility scores were significantly different between the six treatment-outcome scenarios, and active surveillance, non- and minimal-invasive treatments received higher scores. CONCLUSIONS: Active surveillance and non-invasive treatment for localised PCa were the most preferred options by PCa patients and healthy volunteers and received among the highest utility scores. Treatment preferences change after treatment information is received