Discussion
The clinical management of BP-RMS has changed dramatically over the last decades and improvements in chemotherapy, treatment algorithms including delayed surgery and radiation therapy have made organ preservation feasible for many patients. Published oncological outcomes after CS-BT are good with 84% 5yr EFS and 91% OS survival reported by Chargari et al[7]. Unlike our cohort, their series included 12% with metastatic disease, 4% treated for local relapse and 3% with alveolar histology. At a median follow up 3½ years, all our patients were alive without relapse.
For decades, a radical cystectomy with either an incontinent (ileal conduit) or a continent urinary diversion (ileocecal pouch and catheterizable urinary stoma) was standard treatment. In contrast, our CS-BT approach maintained urethral voiding for 85% of patients. This compares to 75% of those treated by CS and HDR-BT for BP-RMS by Fuchs et al[8].
Fuchs et al[8] also used a HDR-BT technique delivering 30-36 Gy via 4 to 7 cannulae in 12 fractions (3Gy per fraction). However, their surgical approach is much more radical aiming for a “R0” or “R1” resection. While surgery was limited to a partial cystectomy in five of the eight BP-RMS patients in their series, three underwent a partial prostatectomy as well as a partial cystectomy. Only one of the latter group enjoys normal voiding; the others having required urinary diversion surgery. Of those with a partial cystecomy, 60% received anticholinergic medication at 4 to 27 months follow up. In our series, 5 (38%) patients were prescribed anticholinergic medication for urgency with variable uptake.
Of note, Rodeberg et al found the amount of radiotherapy administered for BP-RMS impacted on the functional sequelae for the bladder with 17% of patients receiving <40Gy having dysfunction versus 61% receiving >40Gy. Correcting for differences in fractionation and dose-rate between Chagari et al[7], Fuchs et al[8] and this study, the EQD2 doses used for BT are in fact very similar and lie above the 40Gy threshold identified by Rodeberg et al[19]. We specifically examined the radiation burden on the bladder and urethra as organs at risk, but could not find a relation between the radiation exposure of the bladder or urethra and urinary urgency, enuresis or bladder capacity. Schmidt et al[20] compared the urinary tract function between patients receiving CS with HDR-BT and after bladder-preserving surgery without BT. At 3-111months follow up, no difference in normal voiding behaviour (61% (14/23) vs 60% (6/10)) was observed, based on parental reports, voiding frequency charts, uroflow examination with sonographic bladder emptying, but with improved EFS for those managed with HDR-BT.
While an impact on bladder capacity after partial cystectomy would be expected[6], we found no difference in bladder capacity after resection of one third to one fifth of the bladder compared to those having no resection or minimally-invasive polypectomy alone. Longer follow-up will be required to understand whether this will hold true into adulthood. The median percentage of bladder capacity as expected for age across the study population was 86%, which should be adequate for daytime continence. Indeed, 92% of all our patients were dry by day and 62% dry by night. Day- and night-time continence seems lower than the 72% reported by Chargari et al[7]. However, only children, who had not required cystectomy for bladder failure after completing treatment for BP-RMS, for whom data was available and who were aged over 6 years, were included in their continence analysis.
Not only do techniques of conservative surgery and brachytherapy vary between centres, but the selection criteria also differ. Martelli et alconsider tumour extent >1 cm above the trigone on the posterior bladder wall as unsuitable. In contrast, we consider only localised disease, with a tumour diameter less than 5 cm and/or involvement upto a maximum 1/3 of the bladder after a minimum three cycles of chemotherapy as candiates for CS-BT. In our experience, placement of multiple percutanous brachytherapy cannulae affords reliable coverage of the prostate and bladder neck, meaning that only the bladder above the level of the trigone as well as polyps that remain partially mobile in the bladder are at risk of falling outside the radiation field. Unlike Chargari et al[7] and Fuchs et al[8], resection of the prostate is not needed, and almost half the patients required no surgerical resection.
One patient suffered a urethral stricture and another suffered decompensation on a background of high-grade VUR on clamping the suprapubic catheter. Despite this, and contrary to others’ experience[7,8], none of our patients have developed a poorly-compliant small capacity bladder, so far. Whether this is a matter of time or the result of less surgery at the bladder neck remains to be seen. We whole-heartedly agree with previous authors that in- and out-of theatre collaboration by the multi-disciplinary team is essential for optimal tailoring of surgery and brachytherapy to each patient.
Systematic bladder function assessment in children with BP-RMS at a median 3½ years after CS-HDR-BT revealed day-time dryness in 92%, with 85% voiding urethrally, and 62% achieving day-and-night continence at age 4 to 9 years. Bladder capacity remained adequate despite resection of up to one third of the bladder. In comparison to other CS-BT approaches, we report reduced open surgery, with minimally-invasive percutaneous surgery and HDR-BT or brachytherapy alone being suitable for many. So far, all are alive without relapse.