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Quality of Life after Bladder Cancer: A Prospective Study Comparing Patient-related Outcomes after Radical Surgery or Radical Radiotherapy for Bladder Cancer

2015; Elsevier BV; Volume: 28; Issue: 6 Linguagem: Inglês

10.1016/j.clon.2015.12.002

1433-2981

Ashok Nikapota, Jo Cresswell, Sharon A. Appleyard, Susan Catt,

Esophageal Cancer Research and Treatment

Bladder cancer predominantly affects an older population, a demographic that is growing along with the incidence of bladder cancer [[1]CRUK statistics. Available at: www.cancerresearchuk.org/cancer-info/cancerstats/types/bladder/incidence/uk-bladder-cancer-incidence-statistics.Google Scholar]. It is the seventh most common cancer in the UK, the fourth most common in males, with in excess of 10 300 diagnoses in 2011 and 5081 deaths. This disease and its subsequent treatments result in high morbidity irrespective of outcome, which significantly affects the quality of life (QoL) of patients and their carers, and has resource implications for healthcare systems. About 25% of patients present with muscle-invasive bladder cancer (MIBC). Open radical cystectomy with urinary diversion or orthotopic neobladder formation has been considered to be the standard of care, although recent National Institute for Health and Care Excellence (NICE) guidance recommends eligible patients are offered radical surgery or radical radiotherapy with concurrent radiosensitiser [[2]Huddart R.A. Jones R. Choudhury A. A new dawn for bladder cancer? Recommendations from the National Institute for Health and Care Excellence (NICE) on managing bladder cancer.Clin Oncol. 2015; 27: 380-381Abstract Full Text Full Text PDF Scopus (10) Google Scholar]. Neoadjuvant chemotherapy is recommended, improving overall survival by about 5%. About 1500 radical cystectomies are carried out annually in England, an increase of more than 50% over the last 10 years, and most are for MIBC. Improved surgical techniques, enhanced recovery programmes and centralisation [[3]Hounsome L. Verne J. McGrath J. Gillatt D. Trends in operative caseload and mortality rates after radical cystectomy for bladder cancer in England for 1998–2010.Eur Urol. 2015; 67: 1056-1062Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar] have resulted in recently improved perioperative outcomes, with 90 day mortality reducing from 5.2% to 2.1% despite the increase in elderly patients undergoing the procedure. Contemporary surgical series have shown 5 year overall, recurrence-free and cancer-specific survival rates of 57, 48 and 67%, respectively [[4]Yafi F.A. Aprikian J.C. Fradet Y. et al.Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy: a Canadian multicentre experience.BJU Int. 2011; 108: 539-545Crossref PubMed Scopus (124) Google Scholar]. Complication rates after radical cystectomy are relatively frequent in the longer term (over 15 years of follow-up) with ureteric obstruction reported in 14%, stomal problems in 24%, bowel problems in 24%, urinary tract infections in 20% and metabolic derangement (severe metabolic acidosis) in 1%. Renal insufficiency developed in 27%, although in this elderly, comorbid population it is difficult to determine how much of this is attributable to the diversion [[5]Lee R.K. Abol-Enein H. Artibani W. et al.Urinary diversion after radical cystectomy for bladder cancer: options, patient selection, and outcomes.BJU Int. 2014; 113: 11-23Crossref PubMed Scopus (208) Google Scholar]. Continence rates for orthotopic neobladder formation are high (>95% daytime and 76% nocturnal). In more recent studies, intermittent self-catheterisation was required in a minority of patients (10%), with higher rates observed in women [[6]Meyer J.P. Blick C. Arumainayagam N. et al.A three-centre experience of orthotopic neobladder reconstruction after radical cystectomy: revisiting the initial experience, and results of 104 patients.BJU Int. 2009; 103: 680-683Crossref Scopus (54) Google Scholar]. Recent radiotherapy studies, evaluating concurrent regimens with radio-sensitisers, such as chemotherapy or carbogen and nicotinamide, have seen survival outcomes improve and equal results from contemporary surgical series [7Hoskin P.J. Rojas A.M. Bentzen S.M. Saunders M.I. Radiotherapy with concurrent carbogen in bladder carcinoma.J Clin Oncol. 2010; 28: 4912-4918Crossref PubMed Scopus (220) Google Scholar, 8James N.D. Hussain S.A. Hall E. et al.Radiotherapy with or without chemotherapy in muscle invasive bladder cancer.New Engl J Med. 2012; 366: 1477-1488Crossref PubMed Scopus (617) Google Scholar]. Unfortunately, a randomised trial directly comparing surgical and radiotherapy outcomes in this disease has not been completed. The CRUK SPARE trial closed early due to poor recruitment and it is unlikely that another randomised study will be attempted. Most of the published data comparing outcomes from these two treatment modalities is between single centre surgical series and radiotherapy results of multicentre randomised controlled trials. Nevertheless, it appears likely that for some patients these two treatment options confer equivalent outcomes with regard to overall survival [[9]Chen R.C. Organ preservation – will data translate into reality for bladder cancer.Clin Oncol. 2015; 27: 133-135Abstract Full Text Full Text PDF Scopus (2) Google Scholar]. Having two definitive treatment options with equivalent survival end points makes QoL outcomes and health economics essential factors in treatment decision-making for patients, carers and healthcare providers. Studies evaluating QoL outcomes after radical radiotherapy for bladder cancer are largely limited to small, single centre, retrospective series and some using physician-reported or unvalidated questionnaires [10Caffo O. Fellin G. Graffer U. Luciani L. Assessment of quality of life after cystectomy or conservative therapy for patients with infiltrating bladder carcinoma. A survey of self-administered questionnaire.Cancer. 1996; 78: 1089-1097Crossref PubMed Scopus (107) Google Scholar, 11Henningsohn L. Wijkstrom H. Dickman P.W. Bergmark K. Steineck G. Distressful symptoms after radical radiotherapy for urinary bladder cancer.Radiother Oncol. 2002; 62: 215-225Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar, 12Lynch W.J. Jenkins B.J. Fowler C.G. Hope-Stone H.F. Blandy J.P. The quality of life after radical radiotherapy for bladder cancer.BJU. 1992; 70: 519-521PubMed Google Scholar, 13Zietman A.L. Sacco D. Skowronski U. et al.Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of an urodynamic and quality of life study on long-term survivors.J Urol. 2003; 170: 1772-1776Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar]. At the time of assessments, most participants are recurrence-free, biasing the information collected. Unfortunately, comparison between and across published studies is limited by disparate methods and tools used to assess QoL outcomes. Using an unvalidated questionnaire with patients treated with either cystectomy or radiotherapy, Caffo et al. [[10]Caffo O. Fellin G. Graffer U. Luciani L. Assessment of quality of life after cystectomy or conservative therapy for patients with infiltrating bladder carcinoma. A survey of self-administered questionnaire.Cancer. 1996; 78: 1089-1097Crossref PubMed Scopus (107) Google Scholar] found, with 59/93 (63%) evaluable questionnaires, QoL was higher with bladder preservation due to the absence of a stoma, low incidence of urinary symptoms and better sexual functioning. Similar results were reported in a retrospective study comparing patients treated with radiotherapy, those treated with radical cystectomy and urostomy during the same period and a random general population sample [[11]Henningsohn L. Wijkstrom H. Dickman P.W. Bergmark K. Steineck G. Distressful symptoms after radical radiotherapy for urinary bladder cancer.Radiother Oncol. 2002; 62: 215-225Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar]. These data showed that 74% (43/58) of the radiotherapy group had little or no distressing symptoms from the urinary tract and better overall sexual functioning (higher rates of sexual intercourse and ability to ejaculate in men) compared with the surgical group. The rate of gastrointestinal toxicity was not significantly different between the two groups. Notably, the degree to which sexual function is influenced in women is less well documented. Perhaps due to some extent because bladder cancer incidence is less in women, although in one QoL study, women preferred not to answer the question [[13]Zietman A.L. Sacco D. Skowronski U. et al.Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of an urodynamic and quality of life study on long-term survivors.J Urol. 2003; 170: 1772-1776Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar]. The response to radiotherapy is important in determining the impact the treatment has on QoL. Lynch et al. [[12]Lynch W.J. Jenkins B.J. Fowler C.G. Hope-Stone H.F. Blandy J.P. The quality of life after radical radiotherapy for bladder cancer.BJU. 1992; 70: 519-521PubMed Google Scholar] compared the QoL of patients with a complete tumour response after radical radiotherapy with an age- and sex-matched control group. Patients completed the Nottingham Health Profile and physicians reported urinary symptoms utilising the modified Bladder Symptom Score for haematuria, frequency, nocturia, urgency, dysuria, incontinence and rectal symptoms [[12]Lynch W.J. Jenkins B.J. Fowler C.G. Hope-Stone H.F. Blandy J.P. The quality of life after radical radiotherapy for bladder cancer.BJU. 1992; 70: 519-521PubMed Google Scholar]. Both the physician-assessed symptom scores and the patients' scores from the Nottingham Health Profile showed that those with a complete response to radiotherapy had little change in their QoL. Zietman et al. [[13]Zietman A.L. Sacco D. Skowronski U. et al.Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of an urodynamic and quality of life study on long-term survivors.J Urol. 2003; 170: 1772-1776Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar] published comparable findings for 71 patients who were alive and disease-free a median of 6.3 years (range 1.6–14.9) after transurethral resection, chemotherapy and radiotherapy for MIBC [[13]Zietman A.L. Sacco D. Skowronski U. et al.Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of an urodynamic and quality of life study on long-term survivors.J Urol. 2003; 170: 1772-1776Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar]. They used a QoL questionnaire validated for prostate cancer, adapted for the study, and included domains for sexual and physical function, global health functional status and measures of body awareness. A urodynamic evaluation was also carried out, but only 31 completed both the QoL questionnaire and the urodynamic assessment. Most patients had normal bladder function on urodynamic study. However, from the QoL questionnaire, 6% of patients reported flow symptoms, 15% urgency and 19% control problems. Levels of global health-related QoL were found to be high despite 11% of women using protective pads and 14% of patients reporting distress from bowel symptoms. One prospective study assessed bladder function at baseline and then 6 monthly thereafter to 36 months. It found improvement in bladder function after chemoradiation due to primary tumour control and bladder preservation, with satisfactory bladder function for all patients according to LENT-SOMA [[14]Lagrange J.L. Bascoul-Mollevi C. Geoffrois L. et al.Quality of life assessment after concurrent chemoradiation for invasive bladder cancer: results of a multicentre prospective study (GETUG 97-015).Int J Radiat Oncol Biol Phys. 2011; 79: 172-178Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar]. Scores for physical, cognitive, social and emotional functioning were all high after treatment. The QoL of patients for whom local tumour control has not been achieved has not yet been investigated. Studies have extensively reported the QoL outcomes after radical surgery for bladder cancer, mainly for comparisons between orthotopic neobladder and ileal conduit. A recent review of 21 studies including 2285 patients concluded that patients with an orthotopic neobladder had marginally better QoL [[15]Ali A.S. Hayes M.C. Birch B. Dudderidge T. Somani B.K. Health related quality of life (HRQoL) after cystectomy: comparison between orthotopic neobladder and ileal conduit diversion.Eur J Surg Oncol. 2015; 41: 295-299Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar]. Most studies were retrospective, none were randomised, and patients with a neobladder were younger and fitter, potentially biasing results. Two reviews concluded that existing studies had not shown superiority for any particular urinary diversion and although overall QoL after surgery remained good, further evidence from prospective studies was needed using validated disease-specific health-related QoL instruments [16Gerharz E.W. Mansson A. Hunt S. Skinner E.C. Mansson W. Quality of life after cystectomy and urinary diversion: an evidence based analysis.J Urol. 2005; 174: 1729-1736Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar, 17Porter M.P. Penson D.F. Health related quality of life after radical cystectomy and urinary diversion for bladder cancer: a systemic review and critical analysis of the literature.J Urol. 2005; 173: 1318-1322Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar]. QoL after surgery may not be equally as good for women, as Gacci et al. [[18]Gacci M. Saleh O. Cai T. et al.Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicentre study among longterm disease free survivors.Health Qual Life Outcomes. 2013; 11: 43Crossref PubMed Scopus (57) Google Scholar] found that women with a urostomy had lower scores for functional and physical wellbeing and higher levels of fatigue and appetite loss compared with those with an orthotopic neobladder formation, although the small (n = 37) sample size of the study is limiting [[18]Gacci M. Saleh O. Cai T. et al.Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicentre study among longterm disease free survivors.Health Qual Life Outcomes. 2013; 11: 43Crossref PubMed Scopus (57) Google Scholar]. Clearly current comparative data on QoL, psychosocial morbidity and normal functioning are not adequate to fully inform patients with MIBC making treatment decisions. Furthermore, on a population basis, this information is required to enable healthcare providers to commission services appropriately to support these patients. This should lead to improved QoL, reduction in avoidable long-term morbidity and potential financial savings for healthcare services. No studies have included a comparison of health economic outcomes and nor has any of the retrospective work included patients for whom local control has failed after radiotherapy and for those who have an upfront cystectomy. Gathering information on fear of recurrence is also important as this disease has high recurrence rates, and anecdotally patients treated for bladder cancer tell us this worry frequently occurs; mixed populations of cancer survivors show 39–87% incur some degree of fear of recurrence associated with greater symptomatology and poorer QOL [[19]Simard S. Thewes B. Humpries G. et al.Fear of cancer recurrence in adult cancer survivors: a systematic review of quantitative studies.J Cancer Surv. 2013; 7: 300-322Crossref PubMed Scopus (640) Google Scholar]. In summary, QoL outcomes after treatment for MIBC have not been comprehensively studied, despite improved treatment outcomes with the routine use of neoadjuvant chemotherapy, radiosensitisation with chemotherapy and carbogen and nicotinamide. A study of comparative outcomes would assist patients in their decision-making process before embarking on treatment. Undoubtedly, both treatments significantly affect QoL and normal day-to-day functioning. Strategies to minimise this would reduce distress and improve overall functioning. A recent review of patient-reported outcome measures and survivorship in radiotherapy patients highlights the importance of these in improving practice, symptom management and identifying care needs [[20]Faithfull S. Lemanska A. Chen T. Patient-reported outcome measures in radiotherapy: clinical advances and research opportunities in measurement for survivorship.Clin Oncol. 2015; 27: 679-685Abstract Full Text Full Text PDF Scopus (19) Google Scholar]. For healthcare providers, an evaluation of the overall effect of different treatment modalities is essential to enable appropriate commissioning of support services that may mitigate long-term morbidity. Moreover, this fits with a key goal of NHS Outcomes Framework policy to improve QoL in patients with long-term conditions (Domain 2 of the NHS Outcomes Framework [[21]Department of Health NHS Outcomes Framework 2012–13.2011https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/213711/dh_131723.pdfGoogle Scholar]) and emerging international efforts to improve quality of cancer survivor care and was highlighted in the recent NICE guidance [[2]Huddart R.A. Jones R. Choudhury A. A new dawn for bladder cancer? Recommendations from the National Institute for Health and Care Excellence (NICE) on managing bladder cancer.Clin Oncol. 2015; 27: 380-381Abstract Full Text Full Text PDF Scopus (10) Google Scholar]. Planning is underway for a prospective non-randomised QoL study using validated patient-reported outcomes after the radical treatment of MIBC, with the involvement of members of Fight Bladder Cancer, input from the National Cancer Research Institute Psychosocial Studies Group and treating clinicians.