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Article of the week: Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to this post, there is also a video produced by the authors. Please use the comment buttons below to join the conversation.

If you only have time to read one article this week, we recommend this one. 

Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

Jacob Taylor , Ezequiel Becher and Gary D. Steinberg

Department of Urology, NYU Langone Health, New York, NY, USA

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Abstract

Non‐muscle‐invasive bladder cancer (NMIBC) is the most common form of bladder cancer, with frequent recurrences and risk of progression. Risk‐stratified treatment and surveillance protocols are often used to guide management. In 2017, BJUI reviewed guidelines on NMIBC from four major organizations: the American Urological Association/Society of Urological Oncology, the European Association of Urology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence. The present update will review major changes in the guidelines and broadly summarize new recommendations for treatment of NMIBC in an era of bacillus Calmette‐Guérin shortage and immense novel therapy development.

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Video: Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

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Update on the guideline of guidelines: non‐muscle‐invasive bladder cancer

Read the full article

Abstract

Non‐muscle‐invasive bladder cancer (NMIBC) is the most common form of bladder cancer, with frequent recurrences and risk of progression. Risk‐stratified treatment and surveillance protocols are often used to guide management. In 2017, BJUI reviewed guidelines on NMIBC from four major organizations: the American Urological Association/Society of Urological Oncology, the European Association of Urology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence. The present update will review major changes in the guidelines and broadly summarize new recommendations for treatment of NMIBC in an era of bacillus Calmette‐Guérin shortage and immense novel therapy development.

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Residents’ podcast: Health‐related quality of life among non‐muscle‐invasive bladder cancer survivors: a population‐based study

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Maria Uloko is a Urology Resident at the University of Minnesota Hospital. In this podcast she discusses a recent Article of the week:

Health‐related quality of life among non‐muscle‐invasive bladder cancer survivors: a population‐based study

Read the full article

Abstract

Objective

To examine the effect of non‐muscle‐invasive bladder cancer (NMIBC) diagnosis and treatment on survivors’ quality of life (QoL).

Patients and Methods

Of the 5979 patients with NMIBC diagnosed between 2010 and 2014 in North Carolina, 2000 patients were randomly selected to be invited to enroll in this cross‐sectional study. Data were collected by postal mail survey. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core (QLQ‐C30) and the NMIBC‐specific module were included in the survey to measure QoL. Descriptive statistics, t‐tests, anova, and Pearson’s correlation were used to describe demographics and to assess how QoL varied by sex, cancer stage, time since diagnosis, and treatment.

Results

A total of 398 survivors returned questionnaires (response rate: 23.6%). The mean QoL score for QLQ‐C30 (range 0–100, higher = better QoL in all domains but symptoms) for global health status was 73.6, function domain scores ranged from 83.9 to 86.5, and scores for the top five symptoms (insomnia, fatigue, dyspnoea, pain, and financial difficulties) ranged from 14.1 to 24.3. The lowest NMIBC‐specific QoL domain was sexual issues including sexual function, enjoyment, problems, and intimacy. Women had worse bowel problems, sexual function, and sexual enjoyment than men but better sexual intimacy and fewer concerns about contaminating their partner. Stage Ta had the highest global health status, followed by T1 and Tis. QoL did not vary by time since diagnosis except for sexual function. The cystectomy group (n = 21) had worse QoL in sexual function, discomfort with sexual intimacy, sexual enjoyment, and male sexual problems than the non‐cystectomy group (n = 336).

Conclusion

Survivors of NMIBC face a unique burden associated with their diagnosis and the often‐lifelong surveillance and treatment regimens. The finding has important implications for the design of tailored supportive care interventions to improve QoL for NMIBC survivors.

More podcasts

BJUI Podcasts are available on iTunes: https://itunes.apple.com/gb/podcast/bju-international/id1309570262

Article of the week: Health‐related quality of life among non‐muscle‐invasive bladder cancer survivors: a population‐based study

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urology community and a video prepared by the authors; we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one. Happy New Year!

Health‐related quality of life among non‐muscle‐invasive bladder cancer survivors: a population‐based study

Ahrang Jung*†, Matthew E. Nielsen*‡, Jamie L. Crandell†, Mary H. Palmer†, Sophia K. Smith§, Ashley Leak Bryant*† and Deborah K. Mayer*†

*Lineberger Comprehensive Cancer Center,  †School of Nursing, ‡School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, and  §School of Nursing, Duke University, Durham, NC, USA

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Abstract

Objective

To examine the effect of non‐muscle‐invasive bladder cancer (NMIBC) diagnosis and treatment on survivors’ quality of life (QoL).

Patients and Methods

Of the 5979 patients with NMIBC diagnosed between 2010 and 2014 in North Carolina, 2000 patients were randomly selected to be invited to enroll in this cross‐sectional study, which include the use of hemp products from the Hemp Seed distributor business which specialize in this. Data were collected by postal mail survey. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core (QLQ‐C30) and the NMIBC‐specific module were included in the survey to measure QoL. To read the full article check nican .Descriptive statistics, t‐tests, anova, and Pearson’s correlation were used to describe demographics and to assess how QoL varied by sex, cancer stage, time since diagnosis, and treatment.

Results

A total of 398 survivors returned questionnaires (response rate: 23.6%). The mean QoL score for QLQ‐C30 (range 0–100, higher = better QoL in all domains but symptoms) for global health status was 73.6, function domain scores ranged from 83.9 to 86.5, and scores for the top five symptoms (insomnia, fatigue, dyspnoea, pain, and financial difficulties) ranged from 14.1 to 24.3. The lowest NMIBC‐specific QoL domain was sexual issues including sexual function, enjoyment, problems, and intimacy. Women had worse bowel problems, sexual function, and sexual enjoyment than men but better sexual intimacy and fewer concerns about contaminating their partner. Stage Ta had the highest global health status, followed by T1 and Tis. QoL did not vary by time since diagnosis except for sexual function. The cystectomy group (n = 21) had worse QoL in sexual function, discomfort with sexual intimacy, sexual enjoyment, and male sexual problems than the non‐cystectomy group (n = 336).

Conclusion

Survivors of NMIBC face a unique burden associated with their diagnosis and the often‐lifelong surveillance and treatment regimens. The finding has important implications for the design of tailored supportive care interventions to improve QoL for NMIBC survivors.

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Editorial: Beyond bladder cancer surveillance: building a survivorship clinic

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As oncologists, we focus on obtaining the best cancer outcomes possible. The aim of treatment is to maximize survival and help patients live longer. As therapies continue to become more effective, more patients will become survivors. In the ongoing effort to extend the quantity of life left for our patients facing lethal cancers, thinking about the quality of that time is key. For urological oncologists, patients with a new bladder cancer diagnosis will someday face a new set of obstacles as survivors. In addition to surveillance and scans, asking patients about other issues such as their mental health, sexual function and financial solvency are also important.
Regardless of cancer stage, these issues apply to all of our patients with bladder cancer. Patients with non-muscle invasive disease need a seemingly interminable number of cystoscopies, with possible repeat biopsies or intravesical therapies. Patients with muscle-invasive disease undergo urinary diversion that entails significant changes as they will then have a stoma, neobladder or other diversion.
In this issue of BJUI, Jung et al. present a ‘snapshot’ of patients in North Carolina with bladder cancer that examines the impact of treatment on quality of life [1].  The study is valuable because it involves a number of topics that have previously not been studied in such detail. A total of 376 patients returned mailed surveys, a response rate of 24%. Most participants were on average 3 years from their diagnosis, the mean age of participants was 72 years, and the majority of patients were white men. Most participants (approximately three in four) had undergone transurethral resection of bladder tumour as the primary treatment and some (one in three) had received intravesical therapy. As with any work, there are some limitations which include the low overall numbers of participants, low
response rate, and lack of longitudinal data. Despite these limitations, there is still value to studying trends in this space, given the paucity of available data, and the authors offer some valuable insights. This paper provides evidence that for bladder cancer survivorship care, it is important to realize that other important issues exist and impact patient well-being.

• Bladder cancer patients may have financial issues. Bladder cancer patients may face financial toxicity that is in part attributable to the regular need for surveillance in order to identify recurrence or progression of disease.
• Cystectomy recovery can include discussions about sexual function. Patients who have undergone cystectomy may have discomfort with sexual intimacy. This was more common in men. Non-cystectomy patients may have better sexual function. Patients may be concerned about contaminating partners.
• Quality-of-life issues for bladder cancer patients can vary by gender. Men may have better sexual function and enjoyment than women, but also have more discomfort with intimacy and fears of contaminating their partners, while women may have higher levels of constipation and diarrhoea.
• Low risk bladder cancer (vs high risk) can have lower impact on quality of life. Patients with Ta disease had the highest global health status (compared with T1 and Tis). They also had the best physical and social functioning and less fatigue and financial problems. This underscores that Ta disease is different from other stages. As the authors point out, this may be attributable to a low progression risk, which means patients are less likely to need intravesical therapy.
• Sexual health can be affected and improve with time after a bladder cancer diagnosis. Sexual issues can last for years after a diagnosis. Men may face erection or ejaculation problems, and women may have vaginal dryness issues. With time, however, sexual function can improve and sexual function (including extent of sexual activity and interest in sex) was better in survivors further from their diagnosis.

Moving forward, we can use this study to prompt us to think about how our treatments impact our patients. Setting up dedicated survivorship clinics may be one practical strategy to provide this care in a systematic and streamlined way. Beyond treatment-related issues such as recurrence and progression, patients are affected in other ways. Issues with overall health, mental well-being, sleep, or sexual function occur for many. Setting up a standardized approach to cancer care can complement oncological surveillance and promote patient-centred care. A dedicated team, with a provider and physician assistant can create a clinical infrastructure and design a comprehensive template to remind us to query patients on a broader range of issues relevant to their recovery. In doing so, we can help patients with bladder cancer recover, as survivors (Fig. 1).

 

Fig. 1 Select aspects of building a bladder cancer survivorship clinic.

Start by establishing a focused team of providers to help guide more streamlined care
• Nurses, nurse practitioners, physician assistants and physicians can be involved
• Each institution may have a unique infrastructure and use a distinct team set-up to create a clinic
• Administrative support and guidance are important to determine the clinical resources necessary or needed to begin a regular survivorship clinic

Streamline care and consider a template-based or guideline-driven approach to visits
• Based on stage of diagnosis, certain patients may need more regular cystoscopic surveillance while other patients will need follow-up visits that are coordinated with medical oncology and/or radiation oncology

Standardize collection of patient-reported outcomes during follow up visits
• Mental well-being
• Physical activity and exercise
• Sexual health
• Urinary and bowel function
• Financial well-being

Step back to evaluate the progress and iteratively troubleshoot issues as they arise
• Collect patient feedback and provider opinions
• Integrate these insights to improve the form and function of the clinic

by Matthew Mossanen and Stephen L. Chang

Reference

  1. Jung A, Nielsen ME, Crandell JL, et al. Health-related quality of life among non-muscle-invasive bladder cancer survivors: a population-based study. BJU Int 2020; 125: 38–48

Video: Health-related quality of life among non‐muscle‐invasive bladder cancer survivors

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Health‐related quality of life among non‐muscle‐invasive bladder cancer survivors: a population‐based study

Read the full article

Abstract

Objective

To examine the effect of non‐muscle‐invasive bladder cancer (NMIBC) diagnosis and treatment on survivors’ quality of life (QoL).

Patients and Methods

Of the 5979 patients with NMIBC diagnosed between 2010 and 2014 in North Carolina, 2000 patients were randomly selected to be invited to enroll in this cross‐sectional study. Data were collected by postal mail survey. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire‐Core (QLQ‐C30) and the NMIBC‐specific module were included in the survey to measure QoL. Descriptive statistics, t‐tests, anova, and Pearson’s correlation were used to describe demographics and to assess how QoL varied by sex, cancer stage, time since diagnosis, and treatment.

Results

A total of 398 survivors returned questionnaires (response rate: 23.6%). The mean QoL score for QLQ‐C30 (range 0–100, higher = better QoL in all domains but symptoms) for global health status was 73.6, function domain scores ranged from 83.9 to 86.5, and scores for the top five symptoms (insomnia, fatigue, dyspnoea, pain, and financial difficulties) ranged from 14.1 to 24.3. The lowest NMIBC‐specific QoL domain was sexual issues including sexual function, enjoyment, problems, and intimacy. Women had worse bowel problems, sexual function, and sexual enjoyment than men but better sexual intimacy and fewer concerns about contaminating their partner. Stage Ta had the highest global health status, followed by T1 and Tis. QoL did not vary by time since diagnosis except for sexual function. The cystectomy group (n = 21) had worse QoL in sexual function, discomfort with sexual intimacy, sexual enjoyment, and male sexual problems than the non‐cystectomy group (n = 336).

Conclusion

Survivors of NMIBC face a unique burden associated with their diagnosis and the often‐lifelong surveillance and treatment regimens. The finding has important implications for the design of tailored supportive care interventions to improve QoL for NMIBC survivors.

View more videos

 

Visual abstract: Health‐related quality of life among non‐muscle‐invasive bladder cancer survivors: a population‐based study

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Editorial: Predicting progression in T1 non‐muscle‐invasive bladder cancer: back to histology

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Stage pT1 bladder carcinomas (BCs) represent a difficult clinical scenario as they have different outcomes and are associated with a high risk of progression to muscle‐invasive tumours. The optimal therapeutic approach for individual patients in this setting is still unclear: conservative treatment with BCG instillation and intravesical chemotherapy may lead to disease progression and death, while radical cystectomy may represent a mutilating overtreatment for patients with tumours that may have low potential for progression.

The ability to discriminate those patients who will probably progress to carcinoma invading bladder muscle is therefore crucial. Among prognostic factors associated with progression to muscle invasion, tumour grade is one of the most important. In their important paper, van de Putte et al. [1] aimed to compare the prognostic value of the WHO 1973 and 2004 grading systems, the latter being recommended by the AUA guidelines as the most widely accepted in the USA [2], although it has not been proven superior to the other [3].

The authors collected transurethral resections from 601 primary T1 BCs, initially managed conservatively (BCG), from four institutions, and three pathologists reviewed the slides. Importantly, a second transurethral resection was performed if the muscularis propria was absent and/or the initial resection was incomplete. Grade was assigned according to the WHO 1973 (G1–3) and WHO 2004 (low grade [LG] and high grade [HG]) systems. None of the cases was classified as G1. The prognostic value of both grading systems for progression‐free and cancer‐specific survival was then assessed. Notably, the author found WHO1973 G3 to be significantly negatively associated with progression‐free survival and cancer‐specific survival on multivariable analysis, while the WHO 2004 grading system was not. Importantly, intra‐observer variability was assessed in 66 cases and was found to be almost perfect for the WHO 1973 and moderate to substantial for the WHO 2004 system, while inter‐observer variability ranged from moderate to substantial for both systems. One of the reasons for the lack of prognostic potential of the WHO 2004 system, as underscored by the authors, is the fact that the morphological criteria defined in the WHO 2004 system cause an important shift of many cases from the G2 to HG category, rendering it an almost one‐tier system with consequently very few LG tumours. Other studies have assessed the prognostic value of the WHO 1973 and WHO 2004 systems [3] but so far no clear superiority emerged for one system over the other, probably because of relatively low sample sizes.

Other clinical prognostic factors associated with progression to muscle‐invasive tumours include tumour dimension, the presence of multiple lesions, the presence of carcinoma in situ, lymphovascular invasion and level of lamina propria invasion. Regarding the latter prognostic factor, different studies have defined T1 sub‐staging according to invasion above (T1a), within (T1b) or beyond (T1c) the muscularis mucosae and vascular plexus; however, this approach has been found not to be applicable in >40% of cases because of difficulties in identifying the vascular plexus or lack of orientation of the specimens. A more friendly and reproducible method has been proposed by some of the authors of the study, consisting of a categorization of T1 BCs into microinvasive (T1m) and extensively invasive (T1e) tumours, which has been demonstrated to be applicable in 100% of cases and more reproducible [4]. Further study incorporating T1 sub‐staging together with grade may prove very useful.

Different studies have been performed to identify prognostic markers at the molecular level; however, despite huge efforts, no molecular biomarker with prognostic potential is currently suitable for clinical application [5]. Moreover, in six studies that investigated T1 sub‐stage and molecular markers in the same series, T1 sub‐stage showed the highest prognostic value [4]. More recently, subtyping BC into basal‐like and genomically unstable or squamous cell carcinoma‐like tumours has emerged as a promising tool for dividing T1 BCs into low‐ and high‐risk categories [6]; however, such an approach must be combined with the prognostic value of the classic histological variables discussed so far before eventually being integrated into prognostic tools.

In this regard, van de Putte et al. [1] have shown that tumour grade still represents a powerful marker in T1 BC and that the WHO 2004 grading system cannot replace the WHO 1973 system as a prognosticator of T1 BC; therefore, as recommended by the European Association of Urology guidelines, the WHO 1973 grading system categories should always be present in the pathology reports.

 

References

  1. van de Putte EEF, Bosschieter J, van der Kwast TH et al. The World Health Organization 1973 classification system for grade is an important prognosticator in T1 non‐muscle‐invasive bladder cancer. BJU Int 2018; 122: 978–85
  2. Chang SS, Boorjian SA, Chou R et al. Diagnosis and treatment of non‐muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016; 196: 1021–93
  3. Babjuk M, Bohle A, Burger M et al. EAU guidelines on non‐muscle‐invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 2017; 71: 447–614
  4. van Rhijn BW, Liu L, Vis AN et al. Prognostic value of molecular markers, sub‐stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer. BJU Int 2012; 110: 1169–76
  5. Munari E, Chaux A, Maldonado L et al. Cyclin A1 expression predicts progression in pT1 urothelial carcinoma of bladder: a tissue microarray study of 149 patients treated by transurethral resection. Histopathology 2015; 66: 262–9
  6. Patschan O, Sjodahl G, Chebil G et al. A molecular pathologic framework for risk stratification of stage T1 urothelial carcinoma. Eur Urol 2015; 68: 824–32

 

Article of the month: Effect of timing of an immediate instillation of mitomycin C after TUR in 941 patients with NMIBC

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Every month, the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

The effect of timing of an immediate instillation of mitomycin C after transurethral resection in 941 patients with non-muscle-invasive bladder cancer

Judith Bosschieter*, R. Jeroen A. van Moorselaar*, André N. Vis*, Tessa van Ginkel*, Birgit I. Lissenberg‐Witte†, Goedele M.A. Beckers* and Jakko A. Nieuwenhuijzen*

 

Departments of *Urology and †Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

 

Read the full article

Abstract

Objective

To investigate whether the timing of an immediate instillation of mitomycin C (on the day of transurethral resection of bladder tumour [TURBT] or 1 day later) has an impact on time to recurrence of non‐muscle‐invasive bladder cancer (NMIBC).

Patients and Methods

All patients with NMIBC who were enrolled in a prospective trial between 1998 and 2003, and treated with an early mitomycin C instillation (on the day of TURBT or 1 day later), were selected. Statistical analysis was performed with Kaplan–Meier curves and multivariable Cox regression.

Fig. 1 Kaplan–Meier analysis showing time to recurrence for patients treated with an immediate instillation of MMC on the day of TURBT (Day‐0 group) or 1 day after (Day‐1 group).

Results

Administering an instillation of mitomycin C on the day of TURBT or 1 day later did not show a statistically significant difference in time to recurrence in a univariable model (log‐rank P = 0.99). After correcting for the number of scheduled adjuvant instillations, no statistically significant difference could be detected either: hazard ratio 1.05 (95% confidence interval 0.81–1.35, P = 0.74).

Conclusion

These data do not support the hypothesis that a very early instillation (on the day of TURBT) of mitomycin C decreases the risk of recurrence as compared with an early instillation (1 day after TURBT).

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Article of the Month: Effect of the Interval Between First and Second TUR on Outcomes in NMIBC

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Every Month the Editor-in-Chief selects the Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Ilker Gökce, discussing his paper. 

If you only have time to read one article this week, it should be this one.

Significance of time interval between first and second transurethral resection on recurrence and progression rates in patients with high risk non muscle invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guerin

 

Sumer Baltacı, Murat Bozlu*, Asıf Yıldırım†, Mehmet Ilker Gokce, İlker Tinay‡, Guven Aslan§, Cavit Can, Levent Turkeri‡,Ugur Kuyumcuoglu** and Aydın Mungan††

 

Department of Urology, Ankara University School of Medicine, Ankara , *Department of Urology, University of Mersin School of Medicine, Mersin,†Department of Urology, Istanbul Medeniyet University School of Medicine, ‡Department of Urology, Marmara University School of Medicine, Istanbul, §Department of Urology, Dokuz Eylul University School of Medicine Inciralti, Izmir, Department of Urology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, **Department of Urology, Trakya University School of Medicine, Edirne, and ††Department of Urology, Bulent Ecevit University School of Medicine, Zonguldak, Turkey

 

Read the full article
OBJECTIVES

To evaluate the effect of the interval between the initial and second transurethral resection (TUR) on the outcome of patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with maintenance intravesical Bacillus Calmette-Guérin (BCG) therapy.

PATIENTS AND METHODS

We reviewed the data of patients from 10 centres treated for high-risk NMIBC between 2005 and 2012. Patients without a diagnosis of muscle-invasive cancer on second TUR performed ≤90 days after a complete first TUR, and received at least 1 year of maintenance BCG were included in this study. The interval between first and second TUR in addition to other parameters were recorded. Multivariate logistic regression analysis was used to identify predictors of recurrence and progression.

RESULTS

In all, 242 patients were included. The mean (sd, range) follow-up was 29.4 (22.2, 12–96) months. The 3-year recurrence- and progression-free survival rates of patients who underwent second TUR between 14 and 42 days and 43–90 days were 73.6% vs 46.2% (P < 0.001) and 89.1% vs 79.1% (P = 0.006), respectively. On multivariate analysis, the interval to second TUR was found to be a predictor of both recurrence [odds ratio (OR) 3.598, 95% confidence interval (CI) 1.885–8.137; P = 0.001] and progression (OR 2.144, 95% CI 1.447–5.137; P = 0.003).

CONCLUSIONS

The interval between first and second TUR should be ≤42 days in order to attain lower recurrence and progression rates. To our knowledge, this is the first study demonstrating the effect of the interval between first and second TUR on patient outcomes.

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