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Article of the month: Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

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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 editorial written by a prominent member of the urological 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 month, we recommend this one. 

Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

William K. Gray*, Jamie Day*, Tim W. R. Briggs* and Simon Harrison*†

*Getting it Right First Time Programme, NHS England and NHS Improvement, London, UK and †Pinderfields Hospital, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK

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Abstract

Objectives

To investigate volume–outcome relationships in nephrectomy and cystectomy for cancer.

Materials and Methods

Data were extracted from the UK Hospital Episodes Statistics database, which records data on all National Health Service (NHS) hospital admissions in England. Data were included for a 5‐year period (April 2013–March 2018 inclusive) and data on emergency and paediatric admissions were excluded. Data were extracted on the NHS trust and surgeon undertaking the procedure, the surgical technique used (open, laparoscopic or robot‐assisted) and length of hospital stay during the procedure. This dataset was supplemented by data on mortality from the UK Office for National Statistics. A number of volume thresholds and volume measures were investigated. Multilevel modelling was used to adjust for hierarchy and confounding factors.

Results

Data were available for 18 107 nephrectomy and 6762 cystectomy procedures for cancer. There was little evidence of trust or surgeon volume influencing readmission rates or mortality. There was some evidence of shorter length of hospital stay for high‐volume surgeons, although the volume measure and threshold used were important.

Conclusions

We found little evidence that further centralization of nephrectomy or cystectomy for cancer surgery will improve the patient outcomes investigated. It may be that length of stay can be optimized though training and support for lower‐volume centres, rather than further centralization.

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Residents’ Podcast: CUA 2018 review

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Jesse Ory and Andrea Kokorovic
Department of Urology, Dalhousie University, Halifax, NS, Canada

Dalhousie residents Jesse Ory and Andrea Kokorovic sum up the highlights of day 1 at the 2018 Canadian Urological Association annual meeting in Halifax

Song credits
Don’t fear the reaper: Blue oyster cult
Mute city: F Zero
Mortal Kombat Theme: The Immortals
Funky Suspense – Bensound.com

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

 

 

Article of the Month: Comparing survival after RN vs NSS in RCC

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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 month, it should be this one.

Testing the external validity of the EORTC randomized trial 30904 comparing overall survival after radical nephrectomy vs nephron-sparing surgery in contemporary North American patients with renal cell cancer

 

Firas Abdollah, * Sohrab Arora, * Nicolas von Landenberg, †Philipp Gild, ‡Akshay Sood, * Deepansh Dalela, * Quoc-Dien Trinh, §Mani Menon, * and Craig Rogers, *

 

*Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA, †Department of Urology, Marien Hospital Herne, Ruhr-University Bochum, Herne, Germany, ‡Department of Urology, University Medical Centre Hamburg-Eppendorf, Hamburg,Germany and §Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

 

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The European Organization for Research and Treatment of Cancer (EORTC) randomized trial 30904 reported that for solitary renal masses ≤5 cm, radical nephrectomy (RN) was associated with a higher overall survival (OS; primary endpoint): 81%, compared with 76% for nephron-sparing surgery (NSS) at a median follow-up of 9.3 years (P = 0.03). The difference in cancer-specific mortality, however, was not significant. For histologically proven RCC, and after exclusion of patients with positive surgical margins, NSS was associated with equivalent OS compared with RN [1]. It is noteworthy that the renal function outcomes of the two groups in the trial have been reanalysed, showing that renal function does not decline over time after RN, as was expected [2].

The EORTC 30904 trial had difficulty recruiting and randomizing patients, and was criticized for not meeting the accrual goal of 1300 patients. Additionally, the generalizability of the study findings to ‘real-world’ patients has been questioned. Despite the criticism, and more than 20 retrospective studies [3, 4] showing better OS and cancer-specific survival with NSS, this randomized clinical trial (RCT) remains the only available level 1 evidence on this subject. Notably, no study to date has formally examined the external validity [5] of the trial.

For any RCT to be externally valid, its supposedly randomly selected sample must be representative of the general population seen in clinical practice. In this context, we studied patients with localized RCC treated with NSS or RN within the National Cancer Database (NCDB), in an effort to test the external validity of the EORTC 30904. Our objective was not to compare survival outcomes between the two treatment arms, as this is beyond the scope of examining the external validity of an RCT, and such analysis is already available in literature. Instead, our aim was to ascertain if the trial patients were representative of contemporary patients with RCC in the USA, using the NCDB, which captures ~70% of all incident cancer diagnoses in the USA [6].

We identified patients who met the clinical and pathological inclusion criteria of the EORTC 30904 within the NCDB from 2004 to 2013: histologically confirmed RCC; tumour size ≤5 cm; clinically node-negative, non-metastatic disease; no positive surgical margins; and no pT3/4 disease. After exclusions, there were 90 844 assessable patients within the NCDB, of whom 41 588 (45.78%) underwent RN and 49256 (54.22%) underwent NSS. The demographic characteristics, namely, age, gender (percentage of men), presence of comorbidities (yes/no), histology (clear cell/non-clear cell), Fuhrman grade (1, 2, 3 or 4) and surgical approach (open/robotic/laparoscopic) were then compared with the patients enrolled in the EORTC 30904. The statistical significance of differences in categorical variables was tested using the chi-squared test. Unfortunately, the trial did not provide measures of variance (such as standard deviation, or interquartile range) for continuously coded variables; we were therefore unable to test for the statistical significance of differences in these variables. All analyses were performed using SAS 9.4 (SAS Institute, Cary, NC, USA), with a P value <0.05 taken to indicate statistical significance.

The median age of the NCDB cohort was 60.0 years, compared with 62.0 years in the EORTC 30904. The median clinical tumour size in the NCDB was 30 mm, similar to the 30-mm tumour size observed in the trial. The percentage of men was 59.4% in the NCDB vs 65.8% in EORTC 30904 trial (P < 0.001). The NCDB cohort was healthier, with 70.03% patients having no comorbidity vs 62.8% in the trial (P < 0.001). The percentage of patients with clear-cell histology was 81.9% in the NCDB vs 62.9% in the trial (P < 0.001). The trial did not report data on race, while the NCDB had 15.6% non-white patients. Finally, the percentage of patients with high-grade disease (Fuhrman grade ≥3) was 21.1% in the NCDB vs 11.2% in the EORTC 30904 (P < 0.001; Table 1). Notably, in the EORTC 30904 trial, there was no central pathology review.

Table 1. Descriptive statistics of 391 clinically and pathologically eligible patients randomized to nephron-sparing surgery (NSS) or radical nephrectomy (RN) in the European Organization for Research and Treatment of Cancer randomized trial 30904 compared with 40 762 patients within the National Cancer Database with similar inclusion/exclusion criteria, who underwent NSS vs RN, between 2004 and 2013
Variable EORTC 30904 trial NCDB P

  1. EORTC 30904, European Organization for Research and Treatment of Cancer randomized trial 30904; IQR, interquartile range; NCDB, National Cancer Database.
Study period 1992–2003 2004–2013 –
Number of patients clinically and pathologically eligible 391 90 844 –
Median (IQR) age, years 62 (not provided) 60 (51–69) –
Median (IQR) clinical tumour size, mm 30 (not provided) 30 (21–40) –
Men, % 65.8 59.44 <0.001
Race Not provided Non-white 15.6% –
Free of comorbid disease, % 62.8 70.03 <0.001
Clear cell histology, % 62.9 81.9 <0.001
Tumour grade, %
1 22.30 18.08 <0.001
2 66.60 60.78
3 10.50 19.63
4 0.70 1.51
Surgical approach (recorded in NCDB since 2010, n = 15 604), %
Open 100 39.4 <0.001
Robotic 0 34.6
Laparoscopic 0 23.5

Several important observations emerge from these results. First, age and tumour size were similar in the EORTC 30904 trial and the NCDB. These two variables are the most important determinants of mortality and stage of disease, respectively, which implies that the trial was able to recruit patients representative of those seen in ‘real-world’ clinical practice.

Second, there was a higher incidence of high-grade disease and clear-cell histology in the NCDB cohort compared with the EORTC 30904 trial. In other words, patients in the NCDB had more aggressive tumours as compared with patients in the trial. Arguably, such patients are better served with RN, which has a higher probability of completely eradicating the tumour. The survival benefit of RN observed in the trial might therefore be even more evident in clinical practice, where a higher proportion of patients harbour unpredictable aggressive disease.

Finally, the EORTC seems to have recruited patients with a higher comorbidity burden than is generally observed in clinical practice. The significance of this finding is controversial. On the one hand, it might be argued that the higher background mortality of the cohort could have masked the potential OS benefit of NSS by offering this treatment method to sicker patients with limited life expectancy [7]. On the other hand, preserving renal function might be even more important in sicker patients, who have the burden of other comorbidities [8].

The present study has some limitations. An inherent limitation of the NCDB is the lack of information on the performance status of patients. Second, the comparison was between two cohorts separated in time. The mode of treatment and thus, patient selection might have changed over time. The NCDB provides information about surgical approach starting in 2010, and indeed open surgery was performed in only 39.4% of the cases compared with 100% in the trial. More than 15% of patients in the NCDB had missing tumour grade compared with 4% in the trial; however, this proportion was equally distributed between patients undergoing RN and PN in the NCDB (data not shown). Despite the limitations, these findings are significant in the context of the recent debate on contemporary guidelines recommending NSS ‘wherever possible’ in patients with a normal contralateral kidney [9].

In conclusion, our results indicate that, although the EORTC 30904 cohort had somewhat different baseline characteristics than ‘real-world’ patients with small renal masses, none of these differences seem to have the potential to significantly alter the outcomes of the trial. The latter should therefore be considered generalizable to contemporary North American patients with renal masses ≤5 cm.

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Article of the Week: Impact of warm ischaemia time on postoperative renal function after partial nephrectomy for clinical T1 renal cell carcinoma

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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 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.

Impact of warm ischaemia time on postoperative renal function after partial nephrectomy for clinical T1 renal cell carcinoma: a propensity score-matched study

Hakmin Lee*, Byung D. Song*, Seok-Soo Byun*, Sang E. Lee* and Sung K. Hong*†
*Department of Urology, Seoul National University Bundang Hospital, Seongnam, and †Department of Urology, Seoul National University College of Medicine, Seoul, Korea

 

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Objectives

To analyse the effect of prolonged warm ischaemia time (WIT) on long-term renal function after partial nephrectomy (PN), as controversy still exists as to whether prolonged WIT adversely affects the incidence of chronic kidney disease (CKD) after PN.

Patients and Methods

We reviewed data from 1816 patients who underwent PN for a clinical T1 renal tumour. The propensity scores for prolonged WIT were calculated with the shorter WIT group (<30 min) matched to the longer WIT group (≥30 min) in a 2:1 ratio. Multivariate analysis was used to determine independent predictors for occurrence of postoperative CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2] and major renal function deterioration (MRFD; defined as an eGFR decrease of ≥25% postoperatively).

Results

After propensity score matching, there was no significant difference in CKD-free survival between the two WIT groups (P = 0.787). Furthermore, longer WIT did not show any significant associations with postoperative CKD-free survival [hazard ratio (HR) 1.002, 95% confidence interval (CI) 0.989–1.015; P = 0.765) and MRFD-free survival (HR 1.014, 95% CI 1.000–1.028; P = 0.055). From further subgroup analyses using more specific WIT thresholds (≤20, 21–30, 31–40, 41–50, ≥50 min) and status of preoperative CKD, no significant differences were noted in CKD and MRFD-free survival amongst the subgroups (all P > 0.05).

Conclusions

Prolonged WIT was not associated with increased incidence of CKD or MRFD after PN.

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Article of the Week: Management and Outcomes of RMC

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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 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 discussing the paper.

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

Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study

Amishi Y. Shah*, Jose A. Karam*, Gabriel G. Malouf†, Priya Rao*, Zita D. Lim*, Eric Jonasch*, Lianchun Xiao*, Jianjun Gao*, Ulka N. Vaishampayan‡, Daniel Y. Heng§, Elizabeth R. Plimack, Elizabeth A. Guancial**, Chunkit Fung**, Stefanie R. Lowas
††, Pheroze Tamboli*, Kanishka Sircar*, Surena F. Matin*, W. Kimryn Rathmell§§, Christopher G. Wood* and Nizar M. Tannir*

 

*MD Anderson Cancer Center, Houston, TX, USA, †Groupe Hospitalier Pitie-Salpetriere, University Pierre and Marie Curie,
Paris, France, ‡Karmanos Cancer Center, Detroit, MI, USA, §Tom Baker Cancer Center, Calgary, Canada, Fox Chase Cancer Center, Philadelphia, PA, **University of Rochester, Rochester, NY, ††University of Nebraska Medical Center and
Children’s Hospital and Medical Center, Omaha, NE, and §§Vanderbilt-Ingram Cancer Center, Nashville, TN, US

 

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Abstract

Objective

To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS).

Patients and Methods

RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000–2015 at eight academic institutions in North America and France. The Kaplan–Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS.

Results

In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9–48) years and 49 patients (94%) had stage III/IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months.

Conclusions

RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS.

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Editorial: New Strategies for Treating RMC

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In the current issue of BJUI, Shah et al. [1] present a multi-institutional study of 52 patients with renal medullary carcinoma (RMC) collected over a 15-year period. This notoriously lethal and rare form of kidney cancer, associated with sickle cell trait and disease, usually affects young adults. In the study, the median age was 28 years, 94% of the patients presented with stage 3 or 4 disease, and the median overall survival was only 13 months. Nephrectomy, performed in 75% of patients, as opposed to systemic therapy alone, was associated with longer survival (16.4 vs 7.0 months). Of the 45 patients who received platinum- or carboplatinum-based systemic chemotherapy, 13 (29%) had an objective response, while there was no objective response in 28 patients treated with vascular endothelial growth factor-targeted agents, which are highly effective in conventional clear-cell carcinoma of the kidney. Only seven patients survived >2 years, with two long-term survivors at 5 and 9 years after nephrectomy and various combinations of systemic therapy.

Recent reports suggest new insight into this lethal form of kidney cancer, raising hope about the development of effective systemic agents. Calderaro et al. [2] used gene expression profiling, array genomic hybridization, and RNA and whole-exome sequencing to study frozen tissue in five patients with RMC. They reported an interchromosomal balanced translocation that disrupts the SMARCB1 gene, a tumour suppressor on chromosome 22 encoding BAF47 protein, which impairs the SWI/SNF complex regulating chromatin remodelling, which, in turn, leads to increased cyclin D transcription and downstream over-expression of the transcriptional regulator EZH2. EZH2 is the enzymatic subunit of the PRC2 complex and its histone methylation function. EZH2 also has a PRC2-independent role in transcriptional activation and can methylate a number of non-histone proteins. Over-expression of EZH2 can lead to cancer by changing expression of tumour suppressor (pRB) and DNA-damage repair genes. EZH2 over-expression and loss of function mutations are associated with a diverse group of cancers including liver, breast, prostate, endometrial, melanoma, bladder and lymphoma, none of which are as rare as RMC but in which targetable agents can be tested for their ability to disrupt this pathway [3]. Interestingly, SMARCB1 gene truncating and or deletion mutations have been reported in the equally rare and lethal paediatric rhabdoid tumour of the kidney [4] and loss of immunoexpression of SMARCB1 reported in the clinically aggressive collecting duct renal cancer, which is morphologically similar to and often difficult to distinguish from RMC [5].

A number of small-molecule compounds able to target both EZH2 and PRC2 complex are currently undergoing preclinical testing (i.e. DZNEP, E11, EP2005687), phase I trials (GSK126), and phase II trials (EPZ-648, Tazemetostat) [3]. A phase II multicentre study of tazemetostat, a selective small-molecule inhibitor of EZH2, is underway and accruing patients with rare tumours with abnormalities in this pathway, including synovial-cell sarcoma, RMC and rhabdoid tumour of the kidney, for which there are no standard therapies [6]. Contemporary genomic research has great potential to identify such critical oncogenic pathways, shared in both rare and more common malignancies, with the potential for effective drugs to be designed to improve the grave prognosis of RMC and related cancers.

Paul Russo
Weill Cornell School of Medicine Memorial Sloan Kettering Cancer Center New York NY USA

 

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References

 

1 Shah AY, Karam JA, Malouf GG et al. Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study. BJU Int2017; 120: 782–92.

 

2 Calderaro J, Masliah-Planchon J, Richer W et al. Balanced translocations disrupting SMARCB1 are hallmark recurrent genetic alterations in renal medullary carcinomas. Eur Urol2016; 69: 1055–61.

 

3 Kim KH, Roberts CWM. Targeting EZH2 in cancer. Nat Med 2016; 22: 128– 34

 

4 Versteege I, Sevenet N, Lange J et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 1998; 394:203–6

 

5 Elwood H1, Chaux A, Schultz L et al. Immunohistochemical analysis of SMARCB1/INI-1 expression in collecting duct carcinoma. Urology 2011;78: 474

 

 

Video: Management and Outcomes of RMC

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Management and outcomes of patients with renal medullary carcinoma: a multicentre collaborative study

Amishi Y. Shah*, Jose A. Karam*, Gabriel G. Malouf†, Priya Rao*, Zita D. Lim*, Eric Jonasch*, Lianchun Xiao*, Jianjun Gao*, Ulka N. Vaishampayan‡, Daniel Y. Heng§, Elizabeth R. Plimack, Elizabeth A. Guancial**, Chunkit Fung**, Stefanie R. Lowas
††, Pheroze Tamboli*, Kanishka Sircar*, Surena F. Matin*, W. Kimryn Rathmell§§, Christopher G. Wood* and Nizar M. Tannir*

 

*MD Anderson Cancer Center, Houston, TX, USA, †Groupe Hospitalier Pitie-Salpetriere, University Pierre and Marie Curie,
Paris, France, ‡Karmanos Cancer Center, Detroit, MI, USA, §Tom Baker Cancer Center, Calgary, Canada, Fox Chase Cancer Center, Philadelphia, PA, **University of Rochester, Rochester, NY, ††University of Nebraska Medical Center and
Children’s Hospital and Medical Center, Omaha, NE, and §§Vanderbilt-Ingram Cancer Center, Nashville, TN, US

 

Read the full article

Abstract

Objective

To describe the management strategies and outcomes of patients with renal medullary carcinoma (RMC) and characterise predictors of overall survival (OS).

Patients and Methods

RMC is a rare and aggressive malignancy that afflicts young patients with sickle cell trait; there are limited data on management to date. This is a study of patients with RMC who were treated in 2000–2015 at eight academic institutions in North America and France. The Kaplan–Meier method was used to estimate OS, measured from initial RMC diagnosis to date of death. Cox regression analysis was used to determine predictors of OS.

Results

In all, 52 patients (37 males) were identified. The median (range) age at diagnosis was 28 (9–48) years and 49 patients (94%) had stage III/IV. The median OS for all patients was 13.0 months and 38 patients (75%) had nephrectomy. Patients who underwent nephrectomy had superior OS compared to patients who were treated with systemic therapy only (median OS 16.4 vs 7.0 months, P < 0.001). In all, 45 patients received chemotherapy and 13 (29%) had an objective response; 28 patients received targeted therapies, with 8-week median therapy duration and no objective responses. Only seven patients (13%) survived for >24 months.

Conclusions

RMC carries a poor prognosis. Chemotherapy provides palliation and remains the mainstay of therapy, but <20% of patients survive for >24 months, underscoring the need to develop more effective therapy for this rare tumour. In this study, nephrectomy was associated with improved OS.

Read more articles of the week

Article of the Week: Association of HDI with global bladder, kidney, prostate and testis 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 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.

Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality

Alyssa K. Greiman*, James S. Rosoff† and Sandip M. Prasad*‡

 

*Department of Urology, Medical University of South Carolina, Charleston, SC, †Department of Urology, Yale School of Medicine, New Haven, CT, and ‡Department of Surgery, Ralph M. Johnson VA Medical Center, Charleston, SC, USA

 

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Abstract

Objectives

To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development.

Materials and Methods

We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI).

Results

Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5–2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R2 = 0.78), prostate (regression coefficient −1.56, R2 = 0.85), kidney (regression coefficient −1.34, R2 = 0.74), and bladder cancer (regression coefficient −1.01, R2 = 0.80).

Conclusion

While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes.

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Editorial: Human development and its impact on genitourinary cancers

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Using the extensive data from the WHO International Agency for Research on Cancer and the United Nations Human Development Report, Greiman et al. [1] aimed to investigate how human development is associated with incidence and mortality of genitourinary cancers. Even though they generate some interesting descriptive findings, we have to remain critical of these descriptive statistics and carefully assess what needs to be investigated next.

Firstly, despite having highlighted the need for attention to indicators of longevity, education, and income per head when assessing human development, the human development index (HDI) is a rather crude measurement. As a geometric mean of normalised indices for each of these three domains, the HDI simplifies but only captures part of what human development entails. Important indicators of health care such as inequalities, poverty, human security, and empowerment are not reflected in the HDI (www.hdr.undp.org). In the context of cancer incidence and mortality this is an important limitation, as it has for instance been shown that socioeconomic status affects early phase cancer trial referrals, which can be considered as a proxy for access to health care [2]. This inequality has been hypothesised to be linked to more comorbidities and lower education in those who are most deprived – a complex interaction which may not be completely captured by the HDI.

Secondly, registration of incidence and mortality of cancers may vary substantially between countries based on both medical practice and governance. These differences are important when trying to generate hypotheses following the ecological study of Greiman et al. [1]. In the case of bladder cancer, for instance, mortality has been estimated to be 17% in the Netherlands, compared to 22% in the USA, and 50% in the UK. As cancer treatments are expected to be similar in these developed countries, it has been thought that a lower registration of non-muscle-invasive bladder cancer in the UK could explain this higher proportion [3]. Thus, discrepancies in cancer registration, even between developed countries, may limit our awareness of cancer burden.

Thirdly, the study design suffers from ‘ecological fallacy’. The latter refers to the inability to draw causal inference about the effect of the HDI on genitourinary cancer at the individual level, in conjunction with the underlying problem of heterogeneity of exposure levels [4]. This limitation was not mentioned by Greiman et al. [1], but affects their conclusions. The lack of information on, for instance, smoking data, comorbidities, and ethnicity make it difficult to understand how development is affecting cancer incidence or mortality. It would have been interesting to also investigate cancers other than genitourinary cancers because a comparison of different tumour types might have shed light on differences in medical practice or risk factors across countries and help tease out the ecological effect of human development.

Despite the aforementioned limitations, the descriptive analysis by Greiman et al. [1] can be helpful for generating hypotheses – as also outlined by the authors. This ecological effect of human development on incidence and mortality rates of genitourinary cancers is particularly relevant when evaluating the impacts of prevention and intervention programmes for these cancers. Their findings suggest that further investigation is required to examine the hypothesis regarding human development and incidence/mortality of genitourinary cancers. To further elucidate this association, methodological challenges will need to be overcome, as HDI assessment has been criticised for being too crude. Nevertheless, it should be possible to collect more detailed information to allow for an understanding of which components of a country’s collective resources affect cancer incidence and mortality the most, e.g. differences in resources used for cancer detection and treatment.

Mieke Van Hemelrijck
Division of Cancer Studies, Translational Oncology and Urology Research (TOUR), King’s College London, London, UK

 

References

 

1 Greiman AK, Rosoff JS, Prasad SM. Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality. BJU Int2017; 120: 799-807

 

2 Mohd Noor A , Sarker D, Vizor S et al. Effect of patient socioeconomic status on access to early-phase cancer trials. J Clin Oncol 2013; 31: 224– 30.

 

3 Boormans JL, Zwarthoff EC. Limited funds for bladder cancer research and what can we do about it. Bladder Cancer 2016; 2: 49–51

 

4 Morgenstern H . Ecologic studies in epidemiology: concepts, principles, and methods. Annu Rev Public Health 1995; 16: 61–8

 

Residents’ Podcast: When to Perform Preoperative Chest CT for RCC Staging

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Jesse Ory, Kyle Lehmann and Jeff Himmelman

Department of Urology, Dalhousie University, Halifax, NS, Canada

 

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Abstract

Objectives

To provide objective criteria for preoperative staging chest computed tomography (CT) in patients diagnosed with renal cell carcinoma (RCC) because, in the absence of established indications, the decision for preoperative chest CT remains subjective.

Patients and Methods

A total of 1 946 patients undergoing surgical treatment of RCC, whose data were collected in a prospective institutional database, were assessed. The outcome of the study was presence of pulmonary metastases at staging chest CT. A multivariable logistic regression model predicting positive chest CT was fitted. Predictors consisted of preoperative clinical tumour (cT) and nodal (cN) stage, presence of systemic symptoms and platelet count (PLT)/haemoglobin (Hb) ratio.

Results

The rate of positive chest CT was 6% (n = 119). At multivariable logistic regression, ≥cT1b, cN1, systemic symptoms and Hb/PLT ratio were all associated with higher risk of positive chest CT (all P < 0.001). After 2000-sample bootstrap validation, the concordance index was found to be 0.88. At decision-curve analysis, the net benefit of the proposed strategy was superior to the select-all and select-none strategies. Accordingly, if chest CT had been performed when the risk of a positive result was >1%, a negative chest CT would have been spared in 37% of the population and a positive chest CT would have been missed in 0.2% of the population only.

Conclusions

The proposed strategy estimates the risk of positive chest CT at RCC staging with optimum accuracy and the results were statistically and clinically relevant. The findings of the present study support a recommendation for chest CT in patients with ≥cT1b, cN1, systemic symptoms or anaemia and thrombocythemia. Conversely, in patients with cT1a, cN0 without systemic symptoms, anaemia and thrombocythemia, chest CT could be omitted.

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