Comparison of adaptive radiotherapy techniques for the treatment of bladder cancer

Objective

Day-to-day anatomical variations complicate bladder cancer radiotherapy treatment. This work quantifies the impact on target coverage and irradiated normal tissue volume for different adaptive strategies.

Methods

20 patients were retrospectively planned using different three-dimensional conformal radiotherapy treatment strategies for whole-bladder carcinoma: (i) “conventional” treatment used isotropic expansion of the clinical target volume (CTV) by 15 mm to the planning target volume (PTV) for daily treatment; (ii) “plan of the day” used daily volumetric on-treatment imaging [cone beam CT (CBCT)] to select from four available plans with varying superior PTV margins; (iii) “composite” strategies used on-treatment CBCTs from Fractions 1–3 to inform a composite CTV and adapted PTV (5- and 10-mm margins for composite 1 and composite 2, respectively) for subsequent treatment. Target coverage was evaluated from available CBCTs (the first three fractions then the minimum weekly thereafter), and the reduction in the irradiated volume (i.e. within the 95% isodose) was quantified.

Results

Plan of the day improved target coverage (i.e. all of the bladder within the 95% isodose throughout the treatment) relative to conventional treatment (p=0.10), while no such benefit was observed with composite 2. Target coverage was reduced with composite 1 relative to conventional treatment. The mean irradiated volume was reduced by 17.2%, 35.0% and 14.6% relative to conventional treatment, for plan of the day, composite 1 and composite 2, respectively (p<0.01 in all cases). No parameters predictive of large changes in bladder volume later in the treatment were identified.

Conclusions

Adaptive techniques can maintain or improve target coverage while allowing for reduced irradiated volume and possibly reduced toxicity. The plan-of-the-day technique appeared to provide the optimal balance between target coverage and normal tissue sparing.

Advances in knowledge

This study suggests that plan-of-the-day techniques will provide optimal outcomes for adaptive bladder radiotherapy.Muscle-invasive bladder cancer affects over 3000 new patients every year in the UK [1]. Although patients can undergo radical cystectomy, bladder preservation offers comparable outcomes with the added advantage of the patient retaining their own bladder [2]. This means that there is increasing interest in bladder preservation. Patients are treated with maximal transurethral resection of the bladder, neoadjuvant chemotherapy and radiotherapy [3]. Use of concurrent radiosensitisers further improves outcomes [4,5]. With combined modality treatment, local control rates of 70–80% can be achieved. Although this is promising, there is scope for improvement. Higher radiotherapy doses may offer increased local control, but are limited by normal tissue toxicity, with some patients experiencing significant urinary and bowel toxicity [6].Radiotherapy for bladder cancer in the UK involves irradiation of the entire bladder, with a generous margin to account for variations in bladder position, shape and size. However, this is likely to be a suboptimal approach, leading to unnecessarily high doses to normal tissue where bladder volume remains small, while failing to achieve target coverage for patients who encounter increasing bladder volume throughout treatment [7]. Henry et al [8] found that 26% of bladder patients monitored using cone beam CT (CBCT) required replanning owing to increasing bladder volume (53%), decreasing bladder volume (38%) and decreasing rectal volume (9%). The authors recommended development of adaptive radiotherapy protocols for these patients. Strategies aimed at reducing these variations by coaching patients to achieve consistent bladder volumes through drinking protocols have generally met with limited success, despite good patient compliance [9].Daily variations throughout treatment make bladder radiotherapy technically challenging and, with the incidence of bowel toxicity, mean that adaptive strategies could be beneficial. Burridge et al [10] retrospectively investigated the potential of a “plan-of-the-day” approach to this problem, which involved generating three plans based on the bladder volume seen on the radiotherapy planning (RTP) scan with variable superior expansion margins (5, 10 and 15 mm) but uniformity in other directions (15 mm). Based on CBCT images acquired throughout treatment (days 1–5 and weekly thereafter), the optimal plan was selected for treatment. The study demonstrated an average small bowel sparing of 31 cm³ (maximum 76 cm³) compared with non-adaptive techniques.Adaptive techniques are complicated by intrafractional bladder filling: Lotz et al [11] demonstrated that bladder filling rates varied significantly in healthy volunteers, although flow rates for individuals were consistent. To investigate an adaptive plan-of-the-day strategy, Murthy et al [12] acquired megavoltage CT images before and after each treatment fraction, finding that >16% of patients no longer had their bladder contained within the required region at the end of treatment. Studies often account for this effect with an additional 2- to 3-mm margin for intrafractional expansion, although customised approaches have been investigated [13].Alternative adaptive strategies can be broadly classed as “composite” plan approaches. These involve acquisition of several images of patient anatomy on successive days, from which a composite clinical target volume (CTV) [and planning target volume (PTV)] is determined as the union of CTVs observed on each scan. Pos et al [14] used this approach to define a composite CTV based on the observed position on CT scans for the first five fractions, subsequently expanding 10 mm isotropically to a composite PTV. This allowed a 40% reduction in overall irradiated volume with minimal compromise to target coverage.The current work aims to expand on previous studies by making a direct quantitative comparison between different adaptive approaches for whole-bladder radiotherapy within the same patient cohort. Unlike earlier studies, a patient-specific comparison of the appropriateness of each technique will be provided to investigate whether the optimal adaptive strategy varies for particular patients, and whether the optimal strategy could be determined and adopted early in treatment. It was impractical to investigate all of the above approaches owing to subtle variations between investigators and so the focus is on specific examples of each broad approach.