Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicenter study among long-term disease-free survivors

Bladder cancer (BC) ranks ninth in worldwide cancer incidence. It is the 7th most common cancer in men and the 17th most common cancer in women with more than 330,000 new cases each year and more than 130,000 deaths per year [1]. According to the European Association of Urology (EAU) and National Comprehensive Cancer Network guidelines (NCCN), radical cystectomy (RC) is the standard treatment for localized muscle-invasive bladder cancer and high-risk non-muscle-invasive cancers resistant to endovesical chemotherapy [2].

In contemporary series, patients may achieve excellent long-term functional and oncologic outcomes when treated at high-volume institutions by experienced surgeons. Beyond the primary aim of disease control, removal of the bladder requires reconstruction of a lower urinary tract. Surgeons can reconstruct complex urinary diversions that also safeguard patients’ health-related quality of life (HRQOL) [3], but this is a highly morbid surgical procedure associated with significant changes in urinary and sexual function, strained relationships, and psychosocial stress [4]. For this reason, in the last years, the evaluation of HRQOL after such an impacting procedure has garnered increasing interest [5].

Several studies have attempted to evaluate HRQOL following RC and focused on the effects of various types of lower urinary tract reconstruction [6, 7]. Hobisch et al. found that HRQOL was preserved to a higher degree with a continent orthotopic neobladder (ONB-VIP: where last tract of ileal bowel is reconfigured into a sphere and sewn to the urethral stump to facilitate voiding per urethra) compared with an incontinent diversion like cutaneous ureterostomy (CUS: where ureters are connected to the surface of the abdomen with the formation of an opening stoma) and ileal conduit urinary diversion (BK-IC: where the urine is diverted to a bag on the skin, made by short tract of small bowel) [8]. Similarly, Heningssohn et al., compared a cohort of patients that underwent RC and orthotopic bladder substitution with a matched non-operative control group and demonstrated preserved global quality of life [9]. Yet, other studies comparing different types of urinary diversion were unable to confirm superiority of one type of reconstruction with regard to HRQOL [10–12]. Recently, Hedgepeth, et al., showed no difference in body image scores between IC and ONB patients after surgery [13]. However, many of these reports have no long-term follow up, and often include very few recurrence-free female patients.

The aim of this study is to evaluate differences in HRQOL between different forms of urinary diversion in a consecutive series of female who had RC for muscle-invasive bladder cancer. We concentrated on long term (3years or more) recurrence-free females in order to assess HRQOL in a cohort that would not be biased by bladder cancer treatments.

Twelve women were treated with CUS, 16 with BK-IC and 9 with ONB-VIP. Comorbidity counts were 0 in 24 patients, 1-2 in 4 patients, and 3 in 9 patients. All groups were similar according to clinical, pathological and peri-operative characteristics at the time of RC. All patients were disease-free at most recent follow-up (mean 60.1 months; range 36-122 months).

In the last two decades, there has been a growing recognition of the importance of HRQOL among patients undergoing invasive surgical procedures. Therefore, some patients achieve durable cancer-free outcomes. It becomes necessary to safeguard the patients’ HRQOL related to their bladder cancer and its treatment [3].

In our trial we investigated with validated instruments the overall quality of life of a very selected population of patients. In particular, we demonstrated that women undergoing CUS experience a loss of appetite and a worsening of fatigue in daily activities, inducing a worsening of both the physical and emotional well being.

In our paper some aspects are interesting: the study was conducted on long term disease free survivors after RC for clinically localized bladder cancer. This specific population allows us to avoid biases related to the initial postoperative worse HRQOL and/or the fear for tumor recurrence after RC [21]. Moreover, we excluded from our study both adjuvant-related bother and social/emotional implication of disease progression and obtain health-related HRQOL results with minimal biases.

A further strength of this paper is the use of more than one specific validated questionnaire. In the majority of scales and items no differences were found between treatment groups in several clinical trials, such as in our study: therefore, the use of several questionnaires allow us to define the minimal variances across different treatment groups.

The quality of life in patients undergoing cystectomy should take into account many aspects that must be evaluated in order to have data that comes as close as possible to the real situation of the patients themselves. No questionnaire, even if validated, disease specific and well-built, will take into account all the aspects necessary to have a complete evaluation. For this reason we decided to use different and validated questionnaires to evaluate more aspects as possible like: functional, symptoms, global health aspects (EORTC QLQ-C30), the effects of the urostomy (EORTC QLQ -BLM30) and patients well-being (FACT-BL).

Several Authors, by using a single HRQOL questionnaire, did not find any significant correlation between HRQOL and the urinary diversion type. Using several questionnaires it is possible to evaluate different aspects regarding patients HRQOL. Consequently more differences, if exist, can be measured. Furthermore the differences obtained can be evaluated by analyzing several aspect of patients life that only with multiple items, provided by multiple questionnaires, would be possible. Saika et al., by using the EORTC C-30 questionnaire only, concluded that the type of urinary diversion does not appear to be associated with a different HRQOL [22]. In our study, beyond the differences we obtained in EORTC C-30 regarding “appetite loss” and “fatigue” in favor of BK-IC/ONB-VIP, the FACT-BL questionnaire showed a significantly worse HRQOL for CUS compared with BK-IC/VIP-ONB regarding “physical well being” and “emotional well being”. This data can be explained by the fact that patients with CUS showed worse HRQOL outcomes when compared with BK-IC/VIP-ONB merely for “appetite loss” and “fatigue” (EORTC QLQ -C30).

The suggested link between the worsening of “appetite loss” and “fatigue” (EORTC QLQ -C30) and the decline of “physical well being” and “emotional well being” (FACT-BL) could be investigated only by using different questionnaires.

Moreover, the multiplicity of aspects investigated allows us to evaluate possible differences between what is expected based on surgical and anatomical data in literature and the real quality of life of the patient. For example during cystectomy the neurovascular bundle could be damaged [23] causing the worsening of the sexual female quality of life and sexual desire. This aspect should be affect emotional wellbeing inducing a decline of the last one. Under these conditions by analyzing both the sexual aspect (BLM-30) and emotional wellbeing (FACT-BL) we found that there is no relation between them, in fact we observed a decline physical and emotional wellbeing and no differences in sexual function.

The present study has several limitations that should be considered when interpreting our results: in particular, this is a retrospective, cross-sectional, non randomized study in a limited number of patients. It caused a lack of information about baseline pre-treatment HRQOL evaluation, even if all data have been collected and assumed by the case history. However, the possibility of baseline differences in terms of HRQOL among the groups cannot be ignored. Some items, not specific for urological patients, such as mood disturbance or cognitive status were not included in our evaluation. Because this was not a randomized clinical trial, certain biases may have been introduced into analysis that were not properly controlled for and may have impacted the outcome, including the policies regarding urological operations in two different urologic centers involved in this study. In particular, as reported in the “2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy”, there are no evidences to recommend one form of diversion over another one, in females [24]. Consequently, the two referral centers that performed RC did not base the choice for urinary diversion on standard criteria, but have tailored the UD case-by-case. Therefore, we can suppose that the loss of appetite and the fatigue as well as the physical and emotional well-being scores in the CUS group may depend not only on urinary diversion but also on patients’ characteristics.

Finally, as suggested by Studer, there is a lack of specific items regarding the management of the stoma [4]. We need further larger, prospective longitudinal and randomized studies, in order to confirm these findings among the urinary diversion groups.

In conclusion, based on data from a cross-sectional, non randomized study in a limited number of cases, females treated with cutaneous ureterostomy seem to be affected by a worse HRQOL when compared with those treated with Bricker or Paduan Ileal Neobladder, for the deterioration of both the physical and emotional perception of their body image.

Moreover, there is no an exclusive questionnaire that should be used as gold standard to measure HRQOL in female after cystectomy: therefore, several validated questionnaires, investigating different items, scales and scores, have to be used to measure all the aspects of quality of life after RC in female, in future studies.

Further randomized prospective studies, based on the data of our pilot study, are needed to address this important outcome.