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Editorial: Non‐invasive diagnosis and monitoring of urothelial bladder cancer: are we there yet?

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In this issue of BJUI, Ward et al. [1] describe the development of DNA‐based urinary biomarkers for urothelial carcinoma (UC). The genomics of UC have been well characterized through interrogation of tumour issues in institutional series (e.g. the Memorial Sloan Kettering Cancer Center [MSKCC] experience), multi‐institutional collaborations (e.g. The Cancer Genome Atlas [TCGA]) and commercial platforms (e.g. the Foundation Medicine experience) [2]. Until recently, these have been largely academic pursuits, with possible impact on prognostication but limited clinical applicability and utility for therapy selection and monitoring of response; however, with the US Food and Drug Administration approval of erdafitinib several weeks ago, patients with advanced UC will routinely receive genomic assessment for FGFR2/3 mutation or fusion, the targets for this therapy [3]. In due time, it is anticipated that multiple other putative targets with associated therapies (e.g. ERBB2, CDKN2A), as well as potential predictive biomarkers, may also warrant testing.

The evolving landscape in advanced UC makes a non‐invasive biomarker particularly attractive. The authors of the present commentary have previously reported results from a series of 369 patients with advanced UC, demonstrating that genomic alterations in ctDNA could be identified in 91% of patients using a commercially available 73-gene panel [4]. More recently, Christensen et al. [5] assessed a cohort of 68 patients receiving neoadjuvant chemotherapy for muscle‐invasive disease, demonstrating 100% sensitivity and 98% specificity for the detection of relapsed disease with a patient‐specific ctDNA assessment (sequenced to a median target coverage of 105 000×) after cystectomy. Impressively, the data also showed that the dynamics of ctDNA appeared to be more useful than pathological downstaging in predicting relapse.

In contrast to these studies, Ward et al. have developed a 23‐gene panel based on frequently expressed genes in a cohort of 916 UC tissue specimens, largely derived from patients with non‐muscle‐invasive disease. Ultimately, with a cohort of 314 patients with DNA derived from a urinary cell pellet, sequencing identified 645 (71.4%) of 903 mutations detected in tumour. Using urinary supernatant, 353 (80.7%) of 437 mutations were detected. These relatively high sensitivities, if they can be interpreted as such, are promising but do not rise to the level of replacing existing strategies for UC detection, staging and monitoring. Notably, another study demonstrated that urinary ctDNA can be detected with high sensitivity and specificity in patients with localized early‐stage bladder cancer and for after‐treatment surveillance, providing the foundation for further studies evaluating the role of ctDNA in non‐invasive detection, genotyping and monitoring [6].

Beyond its use as a diagnostic tool, it is hoped that urinary ctDNA may also find applications in the selection of therapeutics. To this end, Ward et al. identified FGFR3, PIK3CA, ERCC2 and ERBB2 mutations in 45%, 32%, 14% and 7% of patients, respectively. The frequency of FGFR3 alteration decreased with increasing stage and grade, ranging from 72% in pTaG1 disease to just 13% in ≥pT2 disease, consistent with other reports [7]. These results may guide forthcoming studies evaluating FGFR inhibitors in non‐muscle‐invasive, muscle‐invasive and metastatic disease, where studies are ongoing. In reviewing the potential link between genomic alterations and clinical outcomes, perhaps the most curious finding is that between RAS mutations and improved overall survival (P = 0.04), the only such association found in multivariate analysis. These results stand in sharp contrast to reports in lung cancer, colorectal cancer and multiple other tumour types [8]. A closer look at the deleterious nature and functional impact of NRAS and KRAS mutations seen in this series is certainly warranted, along with further external validation in a more homogenous and larger patient population. There is also the potential application of monitoring treatment response by assessing eradication of urinary ctDNA, a hypothesis that is being evaluated in ongoing studies [9].

How will the results of this and other emerging urinary biomarker studies eventually make their way to the clinic? The answer is simple: incorporation of these biomarkers in prospective therapeutic trials. As the bladder cancer investigative community formulates novel trials for non‐muscle‐invasive and muscle‐invasive disease using targeted therapies, an excellent opportunity exists to correlate urinary, blood and tissue‐based biomarkers and to assess their relative predictive capabilities and clinical utility. Furthermore, with clinical surrogate endpoints likely to drive regulatory approval (e.g. landmark complete response rates for non‐muscle‐invasive disease, or pT0N0 rate for muscle‐invasive disease), a validated urinary biomarker could ultimately offer an alternative biological surrogate endpoint [10]. In an era of genomic revolution, prospective validation can help establish the potential clinical utility of promising biomarkers and help realize the dream of ‘precision oncology’.

by Rohit K. Jain, Petros Grivas and Sumanta K. Pal

References

  1. Ward DG, Gordon NS, Boucher RH et al. Targeted deep sequencing of urothelial bladder cancers and associated urinary DNA: a 23‐gene panel with utility for non‐invasive diagnosis and risk stratification. BJU Int 2019
  2. Schiff JP, Barata PC, Yu EY, Grivas P. Precision therapy in advanced urothelial cancer. Expert Rev Precis Med Drug Dev 2019; 4: 81– 93
  3. FDA grants accelerated approval to erdafitinib for metastatic urothelial carcinoma [press release] 2019.
  4. Agarwal N, Pal SK, Hahn AW et al. Characterization of metastatic urothelial carcinoma via comprehensive genomic profiling of circulating tumor DNA. Cancer 2018; 124: 2115– 24
  5. Christensen E, Birkenkamp‐Demtroder K, Sethi H et al. Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra‐deep sequencing of plasma cell‐free DNA in patients with urothelial bladder carcinoma. J Clin Oncol 2019; 37: 1547– 57
  6. Dudley JC, Schroers‐Martin J, Lazzareschi DV et al. Detection and surveillance of bladder cancer using urine tumor DNA. Cancer Discov 2019; 9: 500– 9
  7. Tomlinson DC, Baldo O, Harnden P, Knowles MA. FGFR3 protein expression and its relationship to mutation status and prognostic variables in bladder cancer. J Pathol 2007; 213: 91– 8
  8. Zhuang R, Li S, Li Q et al. The prognostic value of KRAS mutation by cell‐free DNA in cancer patients: a systematic review and meta‐analysis. PLoS One 2017; 12: e0182562
  9. Abbosh PH, Plimack ER. Molecular and clinical insights into the role and significance of mutated DNA repair genes in bladder cancer. Bladder Cancer 2018; 4: 9– 18
  10. Jarow JP, Lerner SP, Kluetz PG et al. Clinical trial design for the development of new therapies for nonmuscle‐invasive bladder cancer: report of a Food and Drug Administration and American Urological Association public workshop. Urology 2014; 83: 262– 4

 

 

Video: Targeted deep sequencing of urothelial bladder cancers and associated urinary DNA

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Targeted deep sequencing of urothelial bladder cancers and associated urinary DNA: a 23‐gene panel with utility for non‐invasive diagnosis and risk stratification

Read the full article

Abstract

Objectives

To develop a focused panel of somatic mutations (SMs) present in the majority of urothelial bladder cancers (UBCs), to investigate the diagnostic and prognostic utility of this panel, and to compare the identification of SMs in urinary cell‐pellet (cp) DNA and cell‐free (cf) DNA as part of the development of a non‐invasive clinical assay.

Patients and Methods

A panel of SMs was validated by targeted deep‐sequencing of tumour DNA from 956 patients with UBC. In addition, amplicon and capture‐based targeted sequencing measured mutant allele frequencies (MAFs) of SMs in 314 urine cpDNAs and 153 urine cfDNAs. The association of SMs with grade, stage and clinical outcomes was investigated by univariate and multivariate Cox models. Concordance between SMs detected in tumour tissue and cpDNA and cfDNA was assessed.

Results

The panel comprised SMs in 23 genes: TERT (promoter), FGFR3, PIK3CA, TP53, ERCC2, RHOB, ERBB2, HRAS, RXRA, ELF3, CDKN1A, KRAS, KDM6A, AKT1, FBXW7, ERBB3, SF3B1, CTNNB1, BRAF, C3orf70, CREBBP, CDKN2A and NRAS; 93.5–98.3% of UBCs of all grades and stages harboured ≥1 SM (mean: 2.5 SMs/tumour). RAS mutations were associated with better overall survival (P = 0.04). Mutations in RXRA, RHOB and TERT (promoter) were associated with shorter time to recurrence (P < 0.05). MAFs in urinary cfDNA and cpDNA were highly correlated; using a capture‐based approach, >94% of tumour SMs were detected in both cpDNA and cfDNA.

Conclusions

SMs are reliably detected in urinary cpDNA and cfDNA. The technical capability to identify very low MAFs is essential to reliably detect UBC, regardless of the use of cpDNA or cfDNA. This 23‐gene panel shows promise for the non‐invasive diagnosis and risk stratification of UBC.

 

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

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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 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, and‡Department 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

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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 [6, 7]. 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 T, Tanaka H, Koga 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 2019; 124: 242– 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 Bladder, 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT02968732. Accessed April 2019
  4. Fahmy N, Aprikian A, Tanguay S et al. Practice patterns and recurrence after partial cystectomy for bladder cancer. World J Urol 2010; 28: 419– 23
  5. Ploussard G, Daneshmand S, Efstathiou JA et al. Critical analysis of bladder sparing with trimodal therapy in muscle‐invasive bladder cancer: a systematic review. Eur Urol 2014; 66: 120– 37
  6. Huddart RA, Birtle A, Maynard L et al. Clinical and patient‐reported outcomes of SPARE ‐ a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int2017; 120: 639– 50
  7. Huddart RA, Hall E, Lewis R, Birtle A, Group STM. Life and death of spare (selective bladder preservation against radical excision): reflections on why the spare trial closed. BJU Int 2010; 106:753– 5

 

Video: Selective tetramodal bladder‐preservation therapy for MIBC

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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.

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

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Article of the week: Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis

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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 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 month, it should be this one.

Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis

Matthew Mossanen*†‡, Ross E. Krasnow§, Dimitar V. Zlatev*, Wei Shen Tan**, Mark A. Preston*†, Quoc-Dien Trinh*†‡, Adam S. Kibel*†, Guru Sonpavde†, Deborah Schrag†, Benjamin I. Chung†† and Steven L. Chang*†††

*Division of Urology, Harvard Medical School, Brigham and Women’s Hospital, †Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, ‡Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston, MA, Division of Surgery and Interventional Sciences, Department of Urology, University College London, **Department of Urology, Imperial College Healthcare, London, UK, §Department of Urology, Georgetown University, Washington, DC, USA and ††Department of Urology, Stanford University Medical Center, Stanford, CA, USA
Read the full article

Abstract

Objective

To examine the incidence of perioperative complications after radical cystectomy (RC) and assess their impact on 90‐day postoperative mortality during the index stay and upon readmission.

Patients and methods

A total of 57 553 patients with bladder cancer (unweighted cohort: 9137 patients) treated with RC, at 360 hospitals in the USA between 2005 and 2013 within the Premier Healthcare Database, were used for analysis. The 90‐day perioperative mortality was the primary outcome. Multivariable regression was used to predict the probability of mortality; models were adjusted for patient, hospital, and surgical characteristics.

Results

An increase in the number of complications resulted in an increasing predicted probability of mortality, with a precipitous increase if patients had four or more complications compared to one complication during hospitalisation following RC (index stay; 1.0–9.7%, P < 0.001) and during readmission (2.0–13.1%, P < 0.001). A readmission complication nearly doubled the predicted probability of postoperative mortality as compared to an initial complication (3.9% vs 7.4%, P < 0.001). During the initial hospitalisation cardiac‐ (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.9–5.1), pulmonary‐ (OR 4.8, 95% CI 2.8–8.4), and renal‐related (OR 3.6, 95% CI 2–6.7) complications had the most significant impact on the odds of mortality across categories examined.

Conclusions

The number and nature of complications have a distinct impact on mortality after RC. As complications increase there is an associated increase in perioperative mortality.

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Editorial: Radical cystectomy complications and perioperative mortality

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Bladder cancer is the second most prevalent urological cancer, with 25% of cases being muscle invasive, which requires radical therapy as per National Institute for Health and Care Excellence (NICE) guidance [1]. Radical therapy often involves radical cystectomy (RC), which is an incredibly complex operation with common postoperative complications and significant mortality rates [1,2]. It is suspected to have a 30‐day mortality of between 1% and 3%, with this increasing to 10% in the >80 years age group [2, 3], and a 90‐day postoperative complication rate of 50–60% [4].

This complex procedure and its complication rates contribute to a myriad of factors that result in bladder cancer being the most expensive cancer, per patient, to care for and to treat [2, 4]. We congratulate the authors on producing this substantial paper investigating how postoperative complications are associated with overall mortality [5]. Logic dictates that the more complications a patient experiences, the worse the postoperative outcome and, ultimately, the higher the risk of mortality. This paper has succeeded in providing quantifiable data, not only on the overall correlation but by providing adjusted odds ratios (ORs) based upon the nature of the complication.

Whilst a 90‐day prospective study would have been ideal, we recognise this would have been much harder to perform and would have resulted in a much smaller cohort. This retrospective study will therefore suffer from selection bias and unmeasured confounders, as the authors have identified. It should also be noted that these results may not extrapolate to a global population due to data only being collected from a private healthcare system. The coding of clinical diagnosis is often overestimated due to funding that comes with diagnosis and treatments. Despite these biases, this is still the largest set of data investigating the association of RC complications and mortality.

The analysis of the data found that there was a ‘threshold’ limit for the number of complications postoperative patients could experience; patients experiencing four or more complications had a drastic increase in mortality (OR 76.6, P < 0.05) [5]. While all postoperative patients have close monitoring and enhanced recovery pathways, and any patients with postoperative complications will be repeatedly assessed, in an ideal world, patients who have experienced three or more complications would have increased monitoring (high dependency unit/intensive therapy unit).

The breakdown of complications by physiological system was unsurprising, with pulmonary (OR 6.5, P < 0.001), cardiac (OR 4.4, P < 0.001), and renal (OR 2.6, P < 0.001) complications being most associated with increased mortality [5]. Although this information does provide some guidance into specific monitoring methods for high‐risk patients, such as capnography, continuous blood pressure, and renal function monitoring.

While additional demographic and operational information was gathered, the only information collected pertaining to medical health was the Charlson Comorbidity Index (CCI), which meant the authors were unable to ascertain any correlation between the nature of the complications experienced and any predisposing condition of that physiological system. Schulz et al. [6] have recently published a report examining RC morbidity and mortality rates in relation to American Society of Anesthesiologists (ASA) grading and found that patients with an ASA score ≥3 had significantly more high‐grade complications, required more perioperative interventions, and had a higher mortality rate (7.6% vs 3.2%; P = 0.002). Mossanen et al. [5], have taken some of these factors into consideration using the CCI, but unfortunately ASA grade was not part of the data collected.

Due to the nature of the database collection method, the authors were unable to determine other important confounders such as smoking status, exercise tolerance, and the severity/specific details of the complications experienced. Sathianathen et al. [7] showed in October 2018, that smokers were almost twice as likely to have Clavien–Dindo III–V complications following RC, with the most common complications being pneumonia, myocardial infarction, and wound dehiscence.

In our view, Mossanen et al. [5] have provided the urological community with not only quantifiable evidence to support the maxim of ‘more complication, worse outcome’ but they have also identified a vital threshold that can be used clinically to support postoperative patients. This guidance, when paired with clinical judgement, could result in additional monitoring and multi‐disciplinary care in high‐risk patients, ultimately reducing RC mortality rates.

by Alex Hampson, Amy Vincent, Prokar Dasgupta and Nikhil Vasdev

References

  1. National Institute for Health and Care Excellence (NICE). Bladder cancer: diagnosis and management. NICE guideline NG2, February 2015. Available at: https://www.nice.org.uk/guidance/ng2. Accessed September 2018
  2. Shabsigh, A, Korets, R, Vora, KC et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009; 55: 164– 76
  3. Froehner, M, Brausi, MA, Herr, HW, Muto, G, Studer, UE. Complications following radical cystectomy for bladder cancer in the elderly. Eur Urol 2009; 56: 443– 54
  4. Stitzenberg, KB, Chang, Y, Smith, AB, Nielsen, ME. Exploring the burden of inpatient readmissions after major cancer surgery. J Clin Oncol 2015; 33: 455– 64
  5. Mossanen, M, Krasnow, RE, Zlatev, DV et al. Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis. BJU Int2019; 124: 40– 6
  6. Schulz, GB, Grimm, T, Buchner, A et al. Surgical high‐risk patients with ASA ≥ 3 undergoing radical cystectomy: morbidity, mortality, and predictors for major complications in a high‐volume tertiary center. Clin Genitourin Cancer 2018; 16: e1141– 9
  7. Sathianathen, NJ, Weight, CJ, Jarosek, SL, Konety, BR. Increased surgical complications in smokers undergoing radical cystectomy. Bladder Cancer 2018; 4: 403– 9

 

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

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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.

BJUI Podcasts now available on iTunes, subscribe here https://itunes.apple.com/gb/podcast/bju-international/id1309570262

Article of the week: Palliative care use amongst patients with 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 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

 

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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.

 

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