The radiation therapy is a critical component of bladder-preservation treatment (1–3). The goals of radiation therapy are to enhance bladder preservation rates while minimizing the associated toxicities. In terms of dose fractionation, a hypofractionated radiation therapy schedule (55 Gy in 20 fractions) has been recognized as equivalent to conventional fractionation with sequential boost (64–70 Gy in 32–35 fractions) for locoregional control in an individual patient data meta-analysis (8). In addition, the optimal volume of radiation treatment is controversial. The rationale for not treating pelvic lymph nodes is to improve the tolerability of the therapy by excluding normal tissue from the treatment area while achieving an acceptable rate of nodal failure (4.9%) (10). Another issue of radiation treatment is whether to irradiate part of the bladder or the whole bladder. A randomized trial reported that only 7% of tumor recurrences were located outside the irradiated volume for patients who underwent a partial bladder irradiation (11, 12). However, these studies were planned with an empty bladder, in which the gross tumor volume delineation is potentially inaccurate. Furthermore, given the generous isotropic margins with an empty bladder, planning with a 3D conformal technique would rarely spare an unaffected urinary bladder. As a result, these studies failed to decrease the treatment toxicities by using partial bladder irradiation.
Based on these rationales, we decided to treat only the urinary bladder with a hypofractionated radiation schedule. The plan was generated using a mid-bladder volume and the SIB technique to administering a high dose to the tumor bed area with MR monitoring during the treatments.
Importantly, treating bladder cancer is made difficult by the uncertainties of bladder position, shape, and volume during treatment. These stem from the wide variations in nonuniform expansion caused by bladder filling, impacting on both intrafraction and interfraction motion. Research has been conducted to determine the adequacy of target coverage during treatment. Individual urinary-flow rates, bladder-shape-change models, and treatment times have been utilized to generate libraries of accurate treatment volumes (4, 6). Nevertheless, the library plans may not encompass the bladder dimensions on some specific days (13, 14).
MRgRT is an online adaptive tool that enable radiation treatment plans to be adjusted in accordance with actual patient anatomy on each treatment day. Not only does MRgRT ensure target coverage, but it permits doses to the targets and organs at risk to be re-optimized using either an (adapt-to-shape) ATS or (adapt-to-position) ATP strategy (15).
Hunt et al. reported that bladder cancer treatments with MRgRT could achieve a 96.6% target coverage (7). They reported a workflow that started with an empty bladder, anisotropic margins, and ATS re-optimization. However, 14% of their patients need re-optimization with ATP, given the alterations to the bladder shapes and volumes between the image acquisition and the treatment starting time. In addition, the treatments were planned with an empty bladder. This approach did not permit the use of the SIB technique to restrict the application of high-dose volumes to the affected sites only.
In our study, we elected to use the mid-bladder volume, with the aim of prescribing a high dose to the tumor bed and a microscopic dose to the uninvolved bladder. We generated an individual anisotropic PTV margins around the mid-bladder volume from serial images on CT simulation to encompass the target volumes until the end of treatment. We chose to re-optimize with ATP to shorten the treatment planning process to account for patient tolerability of full bladder. As a result, we were able to use this strategy throughout the whole treatment, achieving more than a 96–98% target coverage for both CTV WB and CTV boost. The actual dose delivered to our patient signified the reproducibility of our workflow with a mid-bladder protocol.
Essentially, patient preparation for hydration status and rectal contents was crucial. We recommend the patient to have consistent fluid intake before the scheduled treatment sessions to stabilize the bladder volume during treatment. The use of a low-fiber diet and laxatives is also recommended to help the patient achieve an empty rectum before each treatment session. These approaches decrease the uncertainties associated with the bowel and rectum adjacent to the bladder.
The strength of this study is the reproducible and successful strategy of mid-bladder volume and the SIB technique to decrease excessive radiation doses to the whole urinary bladder. In addition, bladder preparation protocol with personalized anisotropic PTV enhances the success of the ATP approach to shorten the length of the workflow.
Nevertheless, the workflow we have described has several limitations. For one thing, the recontouring accuracy for the CTV boost for both intrafraction and interfraction was a matter of concern. A deformed contour propagation may minimize these uncertainties. As to the dose delivered on a daily basis, dose adjustment was employed mainly for the target coverage (CTV). Therefore, the surrounding normal structures may receive different doses from the reference plan. With ATP, the tissue densities from the initial CT simulation were used for the dose calculation. Therefore, the different soft tissue densities on each specific day resulting from organ motion may not be represented in the actual dose delivered.