Tag Archive for: muscle-invasive bladder cancer

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BJUI at the Indonesian Urological Association Annual Scientific Meeting

The Indonesian Urological Association Annual Scientific meeting was held at The Golden Tulip Hotel, Banjarmasin – 3-5 October 2019.

 

The main conference was preceded by pre-congress workshops at the University of Indonesia Medical Education and Research Institute (IMERI) in Jakarta.

Masterclass with Consultant Urologist Mr Brian Chaplin

Furthermore, the BJUI held a plenary lecture entitled: High Risk Non-Muscle-Invasive Bladder Cancer : The Promise of New Therapies by Consultant Urologist Miss Jo Cresswell, also from the South Tees Hospitals NHS Foundation trust in the UK.

[caption id=”attachment_40134″ align=”aligncenter” width=”243′ label=’ Promoting knowledge: Miss Jo Cresswell at the Masterclass

The conference also featured the increasingly popular 10 and 5 Km Uroruns and a Urowalk starting at 6 and 7am on the Saturday morning.

 

Article of the week: Selective tetramodal bladder‐preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for MIBC

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 urological community, a visual abstract by one of our resident artists and a video produced by the authors. These are 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.

Selective tetramodal bladder‐preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle‐invasive bladder cancer: oncological and functional outcomes of 107 patients

 

Toshiki Kijima*, Hajime Tanaka*, Fumitaka Koga, Hitoshi Masuda, Soichiro Yoshida*, Minato Yokoyama*, Junichiro Ishioka*, Yoh Matsuoka*, Kazutaka Saito*, Kazunori Kihara* and Yasuhisa Fujii*

 

*Department of Urology, Tokyo Medical and Dental University, Department of Urology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, andDepartment of Urology, National Cancer Center Hospital East, Chiba, Japan

 

Read the full article

Abstract

Objectives

To evaluate the oncological and functional outcomes associated with selective tetramodal bladder‐sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND).

Materials and Methods

In the present study, 154 patients with non‐metastatic muscle‐invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder‐preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC‐recurrence‐free survival (RFS); cancer‐specific survival (CSS); overall survival (OS), and cross‐sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36‐item Short‐Form Health Survey (SF‐36) score.

Results

The median follow‐up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder‐preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5‐year MIBC‐RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post‐void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF‐36, patients had favourable scores, equivalent to the age‐matched references in all the QoL scales.

Conclusion

Selective tetramodal bladder‐preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol.

Read more Articles of the week

Editorial: A new horizon for bladder preservation in muscle‐invasive bladder cancer

We are witnessing a shift toward treatment de‐escalation in muscle‐invasive bladder cancer. Patients diagnosed with muscle‐invasive bladder cancer have traditionally faced two treatment options: (1) radical cystectomy with urinary diversion or (2) chemoradiation, both of which can impact quality of life and subsequent morbidity while variably influencing recurrence rates. Recent research has turned toward treatment de‐escalation in an attempt to preserve the bladder while maintaining survival rates. In this issue of BJUI, Kijima et al. [1] propose a tetramodal treatment regimen which combines chemoradiation with partial cystectomy, in an attempt to avoid radical cystectomy without compromising recurrence and survival. Similar ongoing clinical trials are beginning to explore the role of treatment de‐escalation by potentially avoiding cystectomy and/or radiation altogether. Dr Daniel Geynisman is leading a phase II trial at Fox Chase Medical Centre to investigate the role of single‐modality chemotherapy [2]. In that study, therapy is individualized by applying a risk‐adapted approach to identify genetic mutations in cancer cells to predict whether chemotherapy will be effective in eliminating all cancer and preventing future recurrence and metastasis. A related study led by Dr Alexander Kutikov is assessing the reliability of cystoscopic evaluation in predicting pT0 urothelial carcinoma of the bladder at the time of radical cystectomy [3]. By identifying urine biomarkers, investigators could potentially identify those patients who will respond completely to neoadjuvant chemotherapy, thus obviating the need for subsequent cystectomy.

While these studies have not yet provided definitive evidence to forgo definitive therapy (whether it be chemoradiotherapy or radical cystectomy), in this issue of BJUI, Kijima et al. [1] propose similar de‐escalation efforts to promote bladder preservation in a carefully selected population, by preserving quality of life with chemoradiation while addressing the potential increased risk of recurrence with partial cystectomy. The authors report the oncological and functional outcomes of a series of patients who underwent a new tetramodal bladder preservation treatment combination for muscle‐invasive bladder cancer [1]. After patients underwent maximal transurethral bladder tumour resection, induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection, only 4% of patients experienced recurrence of muscle‐invasive bladder cancer over a median follow‐up of 2 years, with an overall cancer recurrence rate of 18% and a 5‐year cancer‐specific survival of 93%.

When comparing these findings with the bladder cancer recurrence rates after partial cystectomy in the setting of muscle‐invasive disease (~40%) [4] and trimodal bladder preservation therapy (11–19%) [5], the findings presented in this paper are remarkable. Although the lower recurrence rate observed in this patient series may be influenced by a shorter follow‐up time than other studies looking at similar outcomes in patients treated for muscle‐invasive bladder cancer, the results of this paper demonstrate a promising frontier in bladder cancer treatment, combining the benefits of trimodal therapy with the extirpative intent of surgery while preserving the bladder. The long‐term (>5 year) cancer‐specific outcomes of these patients, however, remain unknown and are important to examine in order to contribute to our understanding of the true efficacy of this bladder cancer management strategy.

Given that treatment de‐escalation and bladder preservation share the goal of reduced morbidity and improved quality of life, functional outcomes after tetramodal therapy remain unclear yet critical. Differences in functional outcomes between cystectomy and bladder preservation also remain unclear, as randomized trials in this space are challenging to accrue, a lesson learned with the SPARE trial [67]. Certainly, radiation and partial cystectomy are interventions that can decrease bladder capacity and result in irritative LUTS. The extent to which tetramodal therapy impacts these functional outcomes will be important to address moving forward. Despite the absence of a pre‐treatment baseline symptom profile, the overall favourable urinary quality‐of‐life score and reasonable bladder capacity after treatment completion are encouraging and suggest adequate patient tolerability.

As we usher in a new era of personalized medicine in muscle‐invasive bladder cancer, tetramodal bladder preservation treatment may have a role in bladder preservation by decreasing recurrence while maintaining quality of life. We look forward to long‐term data regarding oncological and functional outcomes to determine if this treatment strategy offers a significant benefit when compared with the ‘gold standard’ therapies for muscle‐invasive bladder cancer.

by Pauline Filippou and Angela B Smith

References

  1. Kijima TTanaka HKoga F et al. Selective tetramodal bladder‐preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle‐invasive bladder cancer: oncological and functional outcomes of 107 patients. BJU Int 2019124242– 50
  2. Phase II Trial of Risk Enabled Therapy after Initiating Neoajduvant Chemotherapy for Bladder Cancer (RETAIN BLADDER)2018. Available at: https://www.carislifesciences.com/wp-content/uploads/2018/02/ASCO-GU-A-Phase-II-Trial-of-Risk-Enabled-Therapy-After-Initiating-Neoadjuvant-Chemotherapy-for-Bladder-Cancer-RETAIN-BLADDER.pdf. Accessed April 2019
  3. Cystoscopic Evaluation Predicting pT0 Urothelial Carcinoma of the Bladder2019. Available at: https://clinicaltrials.gov/ct2/show/NCT02968732. Accessed April 2019
  4. Fahmy NAprikian ATanguay S et al. Practice patterns and recurrence after partial cystectomy for bladder cancer. World J Urol 201028419– 23
  5. Ploussard GDaneshmand SEfstathiou JA et al. Critical analysis of bladder sparing with trimodal therapy in muscle‐invasive bladder cancer: a systematic review. Eur Urol 201466120– 37
  6. Huddart RABirtle AMaynard L et al. Clinical and patient‐reported outcomes of SPARE ‐ a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int2017120639– 50
  7. Huddart RAHall ELewis RBirtle AGroup STMLife and death of spare (selective bladder preservation against radical excision): reflections on why the spare trial closed. BJU Int 2010106:753– 5

 

Video: Selective tetramodal bladder‐preservation therapy for MIBC

Selective tetramodal bladder‐preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle‐invasive bladder cancer: oncological and functional outcomes of 107 patients

Abstract

Objectives

To evaluate the oncological and functional outcomes associated with selective tetramodal bladder‐sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND).

Materials and Methods

In the present study, 154 patients with non‐metastatic muscle‐invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder‐preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC‐recurrence‐free survival (RFS); cancer‐specific survival (CSS); overall survival (OS), and cross‐sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36‐item Short‐Form Health Survey (SF‐36) score.

Results

The median follow‐up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder‐preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5‐year MIBC‐RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post‐void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF‐36, patients had favourable scores, equivalent to the age‐matched references in all the QoL scales.

Conclusion

Selective tetramodal bladder‐preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol.

View more videos

Visual abstract: Selective tetramodal bladder‐preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for MIBC

 

See more infographics

Resident’s podcast: Palliative care use amongst patients with bladder cancer

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

Palliative care use amongst patients with bladder cancer

Read the full article

Abstract

Objectives

To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies.

Patients and methods

Using Surveillance, Epidemiology, and End Results‐Medicare data, we identified patients diagnosed with muscle‐invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis.

Results

Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+, or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder‐sparing approach. The adjusted probability of receiving palliative care did not significantly change over time.

Conclusions

Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease‐specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician‐, patient‐, and system‐level barriers to this care.

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Article of the week: Palliative care use amongst patients with bladder cancer

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 urological community, a video produced by the authors and a visual abstract created by Charles Scott and Nurhan Abbud. These are 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.

Palliative care use among patients with bladder cancer

Lee A. Hugar*, Samia H. Lopa*, Jonathan G. Yabes, Justin A. Yu, Robert M. Turner II*, Mina M. Fam*, Liam C. MacLeod*, Benjamin J. Davies*, Angela B. Smith§¶ and Bruce L. Jacobs*

 

*Department of Urology, Department of Medicine, Department of Medicine, Section of Palliative Care and Medical Ethics, University of Pittsburgh School of Medicine, Pittsburgh, PA, §Department of Urology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

 

Read the full article

Abstract

Objectives

To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies.

Patients and methods

Using Surveillance, Epidemiology, and End Results‐Medicare data, we identified patients diagnosed with muscle‐invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis.

Fig. 1. Time from diagnosis to receipt of palliative care. The timing of palliative care receipt for those patients who received palliative care (n = 262). Strata with <11 patients were suppressed in accordance with SEER‐Medicare guidelines

Results

Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+, or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder‐sparing approach. The adjusted probability of receiving palliative care did not significantly change over time.

Conclusions

Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease‐specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician‐, patient‐, and system‐level barriers to this care.

 

Read more Articles of the week

 

 

Video: Palliative care use amongst patients with bladder cancer

Palliative care use amongst patients with bladder cancer

Read the full article

Abstract

Objectives

To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies.

Patients and methods

Using Surveillance, Epidemiology, and End Results‐Medicare data, we identified patients diagnosed with muscle‐invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis.

Results

Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+, or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder‐sparing approach. The adjusted probability of receiving palliative care did not significantly change over time.

Conclusions

Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease‐specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician‐, patient‐, and system‐level barriers to this care.

View more videos

Article of the week: Persistent muscle-invasive BCa after neoadjuvant chemotherapy: an analysis of SEER‐Medicare data

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 urological community. These are 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.

Persistent muscle‐invasive bladder cancer after neoadjuvant chemotherapy: an analysis of Surveillance, Epidemiology and End Results‐Medicare data

Giulia Lane*, Michael Risk*, Yunhua Fan*, Suprita Krishna* and Badrinath Konety*

 

*Department of Urology, University of Minnesota, and Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA
Read the full article

Abstract

Objectives

To evaluate whether patients with persistent muscle‐invasive bladder cancer (MIBC) after undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) have worse overall survival (OS) and cancer‐specific survival (CSS) than patients with similar pathology who undergo RC alone.

Materials and Methods

Using the Surveillance, Epidemiology and End Results (SEER)‐Medicare database, we identified the records of patients with pT2‐4N0M0 disease who underwent RC, with and without NAC, for MIBC between 2004 and 2011. To evaluate survival outcomes in those with MIBC after NAC vs patients with MIBC who underwent RC alone, we used Kaplan–Meier time‐to‐event analysis and Cox proportional hazard regression modelling. Landmark analysis was conducted to mitigate immortal time bias. Propensity scoring was used to decrease the risk of selection bias.

Fig. 2. Propensity‐weighted Kaplan–Meier curves. Overall survival and cancer‐specific survival among patients with persistent pT2‐4N0M0 bladder cancer after radical cystectomy from time of diagnosis. (A) Overall survival and (B) cancer‐specific survival. Neoadjuvant chemotherapy (NAC) + radical cystectomy (RC) in red. RC alone in blue.

Results

Of the 1 886 patients with persistent pT2‐4 disease at the time of RC, 1505 underwent RC alone and 381 received NAC + RC. After adjusting for confounders, the propensity‐weighted risk of death from bladder cancer after diagnosis did not differ between the groups (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.72–1.08; P = 0.23); however, the risk of death from all causes was worse in the RC‐alone group (HR 0.79, 95% CI0.67–0.94; P = 0.006).

Conclusions

Patients who had persistent MIBC after platinum‐based NAC + RC vs RC alone derived an OS benefit but not a CSS benefit from NAC. This may represent a selection bias favouring patients who were selected for NAC; however, the OS benefit was not evident in patients with persistent pT3‐T4N0M0 disease. This study underscores the importance of future research investigating methods to identify patients who will respond to NAC for bladder cancer. It also highlights the need to consider adjuvant therapy in patients who have persistent MIBC after NAC.

Read more Articles of the week

 

 

Editorial: The bladder cancer conundrum: how do we treat the right tumour with the right treatment, at the right time?

The bladder cancer conundrum is how to accurately determine the type of tumour, treatment and timing that is ideal for each patient? This is epitomised by the use of neoadjuvant chemotherapy (NAC) for muscle‐invasive bladder cancer (MIBC). MIBC is a deadly disease; if untreated, the 2‐year mortality rate is 85% [1] and even if treated the overall survival (OS) rate at 5 years is 50%. In this context, NAC is appealing because it may improve outcomes. In 2003, a landmark study by Grossman et al. [2] examined NAC prior to radical cystectomy (RC) for MIBC. The median survival (44 vs 77 months, P = 0.06) and pT0 rates, which equate to the best survival rates (30% vs 15%, P < 0.001), were improved with NAC. A meta‐analysis of 11 randomised control trials in >3000 patients reported an OS benefit of 5% at 5 years with platinum‐based NAC [3]. Whilst NAC improves outcomes, especially for those patients who achieve pT0, it is also important to examine outcomes for patients with persistent MIBC and to determine if NAC is helpful in those patients.

In this issue of the BJUI, Lane et al. [4] attempt to answer this question by examining outcomes for patients with persistent MIBC after RC alone or NAC followed by RC. Using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data, the authors examined 1505 patients that underwent RC alone and 381 patients that received NAC and RC from 2004 to 2011. The authors report that after propensity weighted Kaplan–Meier analysis, the 5‐year OS rate was improved amongst patients that received NAC and RC as compared to patients that had RC alone if there was pT2–T4N0M0 disease on final pathology (43.5% vs 37.2%, P = 0.001). However, there was no difference in cancer‐specific survival (CSS) for NAC with RC compared to only RC (53.7% vs 58.4%, P = 0.76). After adjusting for confounders, the authors found similar results. The use of NAC and RC was found to have an OS benefit (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.67–0.94; P = 0.006) for pT2–4N0M0 patients but not a CSS benefit (HR 0.88, 95% CI 0.72–1.08; P = 0.23).

Since previous studies have established the value of NAC in patients that are down‐staged to pT0 disease, the authors also focused their subset analysis on patients not down‐staged and instead had persistent MIBC. On subset analysis, NAC and RC patients with pT2N0M0 disease had an OS but no CSS benefit. For pT3–T4N0M0 patients, there was no OS or CSS benefit. This may suggest that a subset of non‐responders, such as those with pT2 disease, may experience some benefit from NAC despite persistent disease. Lastly, it is worth noting that whilst NAC improves outcomes, is better tolerated before surgery than adjuvant therapy, and is supported by high‐quality evidence, utilisation remains suboptimal. In this study [4], 381 of 1886 patients (or only 20%) had NAC and only 55% of these received cisplatin‐based therapy. Utilisation patterns vary and updated studies may show different results though. Overall, the authors should be congratulated for a study that is relevant, thoughtful and directed at an important clinical topic.

In this study [4], one issue that is raised is the challenges of accurate preoperative staging. The authors in this paper analysed patients according to pathological stage to limit confounding, as determining the exact stage of patients prior to NAC and RC cannot be done exactly. In this study, pT2 patients had on OS benefit after NAC but pT3–4 patients did not benefit. Clinical staging relies on transurethral resection, imaging and examination under anaesthesia to establish the diagnosis. Without final staging, it is difficult to precisely parse out which patients are clinical T2 vs T3 disease before RC. Predicting which patients are non‐responders is particularly important because these patients may be exposed unnecessarily to the risks of chemotherapy and may have delays in surgery that can negatively impact their outcomes. Therefore, even if the optimal treatment is known, identifying which patients will benefit can be challenging.

Fortunately, there is an exciting future for MIBC on the horizon. First, traditionally bladder cancer staging relies on determining the depth of invasion. In the future, more refined categorisation may help better characterise tumour subtypes. Through innovative multiplatform analyses, an improved understanding of distinct subtypes in bladder cancer has emerged [5]. Consequently, better subtype recognition may herald more targeted, and effective, therapy. Next, it is essential to determine the right type of treatment. Now, NAC is the standard of care for MIBC. However, there are several exciting trials examining other effective options to be used alternatively or synergistically. For example, the use of immunotherapy in the preoperative space is being studied and may shift how we manage MIBC. Lastly, the question of timing is key. Now, the order of surgery and systemic therapy may be a new frontier and perhaps the most significant question we are trying to solve. The possibility of understanding new subtypes of tumours and having new treatment options may require new timing for specific therapies in certain patients. It is conceivable that certain subtypes would be best managed with systemic therapy immediately whilst others with upfront surgery.

Certainly, more work needs to be done. So, what can we do now? We can promote the overall well‐being of our patients. Urologists can be conduits to help patients live healthy lifestyles and engage in behaviours that will promote psychological stability and physical strength. Encouraging daily activity, increasing fruit and vegetable consumption and, if needed, weight loss are options. Smoking cessation represents an imperative opportunity where urologists can make a positive impact [6]. Prehabilitation programmes focused on preparation for surgery can be done during NAC or while waiting for surgery and incorporate these elements. In this way, waiting time is leveraged to make small but cumulative improvements – ‘a little bit at a time’ is possible.

For now, we will continue to study the bladder cancer conundrum: subtypes of tumours, various treatments, and the best timing for therapy. Regardless of these results, it is likely patients with bladder cancer will still need some combination of surgery, systematic therapy and supportive care while they heal. In the interim, promoting well‐being is one way to help patients live healthier lives whilst making them more resilient to undergo whatever treatments may emerge next.

by Matthew Mossanen and Adam S. Kibel

References

  1. Prout, GRMarshall, VFThe prognosis with untreated bladder tumors. Cancer 19569551– 8
  2. Grossman, HBNatale, RBTangen, CM et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003349859– 66
  3. Advanced Bladder Cancer Overview CollaborationNeoadjuvant chemotherapy for invasive bladder cancer. Cochrane Database Syst Rev 20052CD005246.
  4. Lane, GRisk, MFan, YKrishna, SKonety, BPersistent muscle‐invasive bladder cancer after neoadjuvant chemotherapy: an analysis of Surveillance, Epidemiology and End Results‐Medicare dataBJU Int 2019123818– 25
  5. Robertson, AGKim, JAl‐Ahmadie, H et al. Comprehensive molecular characterization of muscle‐invasive bladder cancer. Cell 20181741033
  6. Mossanen, MCaldwell, JSonpavde, GLehmann, LSTreating patients with bladder cancer: is there an ethical obligation to include smoking cessation counseling? J Clin Oncol 2018; 36: 3189– 91
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