Background/Objectives: Randomised trials show that screening with prostate-specific antigen (PSA) and systematic prostate biopsies can reduce prostate cancer mortality but leads to high rates of overdiagnosis. Today, improved diagnostic methods more selectively detect potentially lethal, high-grade prostate cancer. Methods: This is a narrative review of modern diagnostic methods, ongoing trials, national policies and knowledge gaps related to screening and early detection of prostate cancer. Results: Screening intervals can be prolonged in men with PSA values below around 1 ng/mL as these men are at very low long-term risk of prostate cancer death. Overdiagnosis can be reduced by magnetic resonance imaging (MRI) and lesion-targeted prostate biopsies. Risk calculators and ancillary biomarkers can select men for further investigation and thereby reduce resource needs. These new methods are evaluated in large, randomised screening trials. The remaining knowledge gaps include optimal PSA cut-offs, screening intervals, start and stop ages, and the long-term balance between benefits and harm. Until recently, almost no national healthcare authority recommended population-based screening for prostate cancer. Now, the European Union Council recommends an evaluation of the feasibility of organised, risk-stratified screening. This has led to several pilot projects. In some other parts of the world, such as sub-Saharan Africa and the Caribbean, such initiatives are lacking despite high prostate cancer mortality rates. Conclusions: Risk-stratified prostate cancer screening including MRI and targeted biopsy reduces overdiagnosis. Results from ongoing research are needed to optimise screening protocols and to define long-term benefits and harms. Initiatives for early detection and screening are emerging across the world but are still lacking in many countries with high prostate cancer mortality.

The extension of tumour thrombus into the inferior vena cava (IVC) poses a significant surgical challenge, making preoperative investigation and planning crucial. The most common scenario involves a primary renal malignancy that invades the renal vein and extends into the IVC. A key consideration in surgical planning is determining the proximal extent of the tumour thrombus. A CT scan and MRI of the IVC are valuable diagnostic tools, while a liver Doppler ultrasound can be performed to assess for involvement of the hepatic veins and to evaluate any potential obstruction to hepatic outflow. Various classification systems have been described [1]. The traditional classification delineates four levels of thrombus extent: level 1 (thrombus <2cm above the renal vein), level 2 (thrombus below the infra-hepatic vena cava), level 3 (thrombus involving the retro hepatic vena cava but located below the diaphragm), and level 4 (thrombus extending into the atrium) [2]. While levels 1 and 2 do not significantly complicate the surgical approach, levels 3 and 4 present increased risks that necessitate careful planning and a multidisciplinary strategy. Specifically, level 4 thrombus and level 3 thrombus with obstruction of the hepatic veins and Budd-Chiari syndrome require the integration of cardiopulmonary bypass and deep hypothermic circulatory arrest without mobilisation of the right lobe of the liver. In this report, we outline the proposed surgical steps for managing level 3 IVC thrombus arising from right-sided renal cell carcinoma with a proximal extension just below the hepatic veins, achieved through collaboration between liver and urology teams.

Objectives: Perioperative blood transfusion (PBT) has been associated with worse survival after radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). Here, we evaluated the association between PBT and survival after RC that was preceded by neoadjuvant chemotherapy (NAC). Methods: A retrospective analysis was performed on 949 patients with cT2-4aN0M0 bladder cancer who received NAC prior to RC between 2000 and 2013 at 19 centers. Kaplan–Meier estimates of overall survival (OS) were made. Presumed risk factors for OS were analyzed using Cox regression analysis. PBT was defined by the administration of any packed red blood cells during surgery or during the post-operative hospital stay. Results: A transfusion was given to 608 patients (64%). Transfused patients were more likely to have adverse clinical and pathologic parameters, including clinical stage and performance status. Transfused patients had worse OS (p = 0.01). On multivariable Cox regression, PBT was found to be independently associated with worse OS (HR 1.53 (95% CI 1.13–2.08), p = 0.007). Conclusions: PBT is common after NAC and RC, which may be linked, in part, to the anemia induced by NAC. PBT was associated with several adverse risk factors that correlate with poor outcomes after NAC and RC, and it was an independent predictor of adverse OS on multivariable analysis. Further study should determine if measures to avoid blood loss can reduce the need for PBT and thereby improve patient outcomes.

Prostate cancer (PCa) is a significant healthcare problem worldwide. Current diagnosis and treatment methods are limited by a lack of precise in vivo tissue analysis methods. Real-time cancer identification and grading could dramatically improve current protocols. Here, we report the testing of a thin optical probe using Raman spectroscopy (RS) and classification methods to detect and grade PCa accurately in real-time. We present the first clinical trial on fresh ex vivo biopsy cores from an 84 patient cohort. Findings from 2395 spectra measured on 599 biopsy cores show high accuracy for diagnosing and grading PCa. We can detect clinically significant PCa from benign and clinically insignificant PCa with 90% sensitivity and 80.2% specificity. We also demonstrate the ability to differentiate cancer grades with 90% sensitivity and specificity ≥82.8%. This work demonstrates the utility of RS for real-time PCa detection and grading during routine transrectal biopsy appointments.

BACKGROUND:Prostate cancer is now the most common cancer in men in Australia. Men should be aware of the potential risk of significant prostate cancer despite the lack of symptoms. Screening for prostate cancer using prostate-specific antigen (PSA) has been controversial. General practice guidelines can be confusing leading to men not being tested for prostate cancer. Reasons cited include overdiagnosis and overtreatment with associated morbidity.OBJECTIVE:This article aims to highlight the current evidence for PSA testing and advocate for updating outdated guidelines and resources.DISCUSSION:Current evidence shows that a risk-stratified approach to PSA screening helps to assess that risk. Recent studies show improved survival rates with early intervention compared with observation/delayed treatment. Imaging, including magnetic resonance imaging and prostate-specific membrane antigen positron emission tomography, have made a significant difference in the management pathway. Biopsy techniques have progressed to minimise sepsis risk. Quality and patient-reported outcomes registry data highlight the increased use of active surveillance in patients with low to intermediate risk of prostate cancer, reducing treatment-associated harms in men with low risk of progression. There have also been improvements in medical therapeutics for advanced disease.

Robot-assisted radical prostatectomy (RARP) for prostate cancer is now well-established in settings where robotic surgical systems are available. The number of RARP per year overtook open radical prostatectomy (ORP) in 2009 in the United States of America (U.S.A),1 in 2012 in England,2 and in 2015 in Australia.3 The proportion of RARP increased to 85% in the United States in 2013,1 93% in England in 2018,2 and 65% in Australia in 2019.3 Similar trends have been observed in other advanced economies.4-6 North Shore Hospital is the only public hospital in Aotearoa New Zealand (AoNZ) with a da Vinci Surgical System (dVSS) (Intuitive Surgical, Sunnyvale, California, USA), and its first RARP was performed in late 2021. Figure 1 outlines the trends for prostatectomy and new prostate cancer registrations in AoNZ from 2010 to 2020 using anonymous procedure-only data from the AoNZ distributor of the dVSS (Device Technologies, Auckland, New Zealand), the National Minimum Dataset for hospital events (National Collections and Reporting, Manatū Hauora, Ministry of Health) and publicly available new prostate cancer registrations from the New Zealand Cancer Registry. RARP comprised 10.5% (n = 90) of the total cases of radical prostatectomy in 2010/2011, rising to 27.6% (n = 436) in 2019/2020. The volume of RARP surpassed ORP in private hospitals in 2016/2017 and made up 60% of private radical prostatectomies in 2019/2020. Access to RARP in AoNZ has historically been through private health insurance or the ability to pay. NZ Health Survey data showed only a third of the population have private health insurance, with Māori and those living in lower deprivation areas less likely to have health insurance.7 Only 23% of Māori and 19% of Pacific peoples reported having private health insurance compared to 37% of European/Other. This is likely reflected in the different treatment rates between Māori and European/Other for publicly funded prostate cancer therapy.8 Māori and Pacific patients may derive additional benefits from the robot-assisted approach due to the discrepant clinical nature of prostate cancer at presentation combined with patient-specific anatomical considerations.9, 10 The provision of RARP in public is a step towards Te Pae Tata, the interim New Zealand Health plan, ‘creating equitable access to services’.11 Neither the American nor European Association guidelines for prostate cancer12, 13 make any recommendations regarding the approach for radical prostatectomy, and the NICE guidelines14 suggest a minimum of 150 cases per robotic surgical system to ensure cost-effectiveness. So, what then is the ‘value’ of RARP in the AoNZ public healthcare system? Assessments of value are afforded high regard when considering adopting technology in health service investments. Traditionally the focus on value has been related to monetary costs and clinical benefits. In a system that prioritizes patient and whānau values,11 some important benefits are not readily calculable. For example, in prostate cancer, sexual dysfunction has been found to be the most important patient-reported functional outcome associated with treatment-related regret and changes in quality of life and outcome satisfaction for patients and their affected partners.15, 16 Other relevant considerations of even the most contemporary cost-analysis literature reveal multiple assumptions not relevant to the AoNZ context and have used low-quality evidence and simplistic approaches.14, 17 An intervention may be more costly, but if it significantly reduces disparities in outcomes, it may be more valuable. For instance, the cost of an equitable tertiary referral service must include the costs of travel and accommodation support for patients and whānau/support persons from regions where such services are not readily available. A constructive technology assessment, as opposed to the more traditional health technology assessment, that incorporates the context of implementation with consideration of the patient-related and socio-organizational factors, may be a more realistic paradigm.18 Furthermore, implementing RARP has additional benefits beyond using the device itself that require funders to consider the whole system. The contemporaneous development of evidence-based education and training, such as simulation and proficiency-based curricula, have led to advancements in RARP previously unavailable to ORP.19, 20 Consequently, up-to-date analyses of the learning curve suggest that fewer cases are required to achieve adequate cancer control for RARP compared to ORP.21 The ready availability of video recording in RARP has catalysed the novel application of artificial intelligence and quality assurance to advance technical skills, patient safety, and clinically relevant outcomes.22, 23 This has particular relevance for the AoNZ health context, where consumers have limited choice and value transparency of health professionals' competence to be objectively demonstratable.24 The value of RARP in public hospitals extends beyond the specific procedure and indication. Unlike a discrete device, with a singular function and narrow indication,25 the robotic surgical system is multipurpose, with level one evidence of superiority for cystectomy and intracorporeal reconstruction for bladder cancer,26 and emerging utility in other specialities such as general surgery.27, 28 Public hospitals are the primary setting for training the future urology workforce. As many advanced economies overseas have transitioned to robot-assisted surgery (RAS) for complex urological procedures, the implementation of RAS may contribute to addressing the ‘global competition for trained and experienced people’ outlined in Te Pae Tata.11 Expanding RARP to more public hospitals will provide the opportunity for returning fellowship-trained specialists to utilize their expertise, including in advanced therapies, in the public health system for our local population. It is imperative to increase opportunities for local trainees to develop the necessary skills in a speciality where RAS will increasingly feature. The recruitment and retention of specialists will provide a further return on public investment. Equitable access is a requisite for just distribution of health services, but in isolation is not sufficient to realize Te Pae Tata's aspiration of ‘outcomes and equity for people with cancer’.11 The implementation of RARP must not become another source of variations in outcomes. RARP remains only one component in the endeavour to improve the quality of care for patients with prostate cancer. However, it has the potential to significantly contribute to at least five out of seven treatment-related quality performance indicators outlined by Te Aho o Te Kahu.29 As our public health system faces multiple challenges to balance numerous needs, it may be an opportune time to consider a multistakeholder (including patients) engagement in determining the expansion of RARP. Phillip Pinhao Chao: Conceptualization; data curation; funding acquisition; investigation; methodology; project administration; visualization; writing – original draft; writing – review and editing. Jonathan Barnes Koea: Funding acquisition; investigation; methodology; supervision; validation; writing – review and editing. Kamran Zargar-Shoshtari: Investigation; validation; writing – review and editing. Jason Du: Investigation; validation; writing – review and editing. Andrew Graham Hill: Funding acquisition; investigation; methodology; supervision; validation; writing – review and editing. Sanket Srinivasa: Funding acquisition; investigation; methodology; project administration; supervision; validation; writing – review and editing. Phillip Chao is the recipient of a Health Research Council of New Zealand (HRC) Clinical Research Training Fellowship (Reference number: 22/034). The authors thank Device Technologies, Auckland and Manatū Hauora, Wellington for providing the data without cost or restrictions. The HRC, Device Technologies and Manatū Hauora had no role in the preparation or decision to submit the manuscript. The views and opinions expressed in this manuscript are those of the authors and do not necessarily reflect the HRC, Device Technologies or Manatū Hauora. Open access publishing facilitated by The University of Auckland, as part of the Wiley - The University of Auckland agreement via the Council of Australian University Librarians. Professor Jonathan B. Koea and Professor Andrew G. Hill are an Editorial Board members of ANZ Journal of Surgery and co-authors of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication.

A fibre optic probe is applied to discriminate between healthy and cancerous prostate tissue using Raman Spectroscopy. Results from fresh human biopsy cores show excellent classification between cancerous and healthy tissue, and between cancer grades.

In the original article, the name of author Sia Daneshmand was incorrectly abbreviated as D. Daneshmand. The correct version is given in the above author list.Conflicts of interest: The authors have nothing to disclose. In the original article, the name of author Sia Daneshmand was incorrectly abbreviated as D. Daneshmand. The correct version is given in the above author list. Conflicts of interest: The authors have nothing to disclose. Nomogram Predicting Bladder Cancer–specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International ConsortiumEuropean Urology FocusVol. 7Issue 6PreviewTake Home Message We developed a nomogram predicting bladder cancer–specific mortality after neoadjuvant chemotherapy and radical cystectomy in a large, multi-institutional patient cohort. Full-Text PDF

Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50

A Raman Spectroscopy probe is used to discriminate between healthy and cancerous prostate tissue. Results from ex vivo human biopsy tissue are presented. Results show excellent classification performance between the different types of tissue.

Prostate cancer is a significant healthcare problem in many western countries. In response to the current need for more accurate and less invasive real-time diagnosis systems, we are developing a thin optical probe that uses Raman spectroscopy to detect prostate cancer in vivo and in real-time. We present results from an ex vivo study on fresh biopsy cores seconds after collection. Findings show that our system can identify prostate cancer from benign tissue, as well as differentiate tissue with different Gleason patterns. We aim to apply this technique, in the near future, for real-time PCa identification during routine biopsy appointments.

Machine learning has shown great potential for classifying diverse samples in biomedical applications based on their Raman spectra. However, the acquired spectra typically require several preprocessing steps before standard machine learning algorithms can accurately and reliably classify them. To simplify this workflow and enable future growth of this technology, we present a unified solution for classifying biological Raman spectra without any need of prepossessing, including denoising and baseline establishment. This method is developed based on a custom version of a convolutional neural network (CNN) elicited from ResNet architecture, combined with our proposed data augmentation technique. The superiority of this method compared to conventional classification techniques is shown by applying it to Raman spectra of different grades of bladder cancer tissue and surface enhanced Raman spectroscopy (SERS) spectra of various strains of E. Coli extracellular vesicles (EVs). These results show that our method is far more robust compared to its conventional counterparts when dealing with the various kinds of spectral baselines produced by different Raman spectrometers.

Background Positive surgical margins (PSM) after radical prostatectomy (RP) have been associated with increased risk of biochemical recurrence (BCR). This is heavily influenced by other clinicopathological factors. This study aims to assess the impact of the extent and location of PSM on BCR following RP for Gleason 7 carcinoma of the prostate (CaP). Materials and Methods All men treated with RP between 2008 and 2017 in our region for localized or locally advanced Gleason 7 CaP, were included. Clinical (age, year, preoperative prostate specific antigen) and pathological (prostate weight, positive or negative surgical margins, International Society of Urological Pathology [ISUP] grade, T stage) data were collected. PSM were subcategorised according to Extent into favourable (unifocal and <3 mm in length) or unfavourable (multifocal or >= 3 mm in length), and Location into apical only or others. The outcome was the risk of BCR which was calculated with univariable and multivariable regression models and reported as hazard ratio (HR) with 95% confidence interval (CI). Results The cohort constituted of 1433 men. Majority had ISUP 2 (71.2%) or localized (62%) disease. Men with PSM (n = 506) were at greater risk of BCR when compared to those with negative margins (adjusted HR = 1.52, [CI: 1.14-2.04], p = .005). Similar observation was demonstrated for both PSM location subgroups. As for the PSM extent category, only men with unfavourable PSM demonstrated an increase in BCR risk over negative margin (adjusted HR = 1.67, [CI: 1.23-2.28], p = .001). Conclusions Within this study settings, PSM were generally associated with increased BCR risk. This, however, was not demonstrated in favourable PSM extent cases. Observation rather than active treatment in these men should be considered.

Background: : Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. Objective: : To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. Design, setting, and participants: : Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. Outcome measurements and statistical analysis: : A nomogram for bladder cancer- specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. Results and limitations: : A total of 640 patients were identified. Downstaging to nonMIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7- 4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. Conclusions: : We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. Patient summary: : In this report, we looked at the outcomes of patients with muscle invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability. (c) 2020 Published by Elsevier B.V. on behalf of European Association of Urology.

Extracellular vesicles (EVs) are micro and nanoscale lipid-enclosed packages that have shown potential as liquid biopsy targets for cancer because their structure and contents reflect their cell of origin. However, progress towards the clinical applications of EVs has been hindered due to the low abundance of disease-specific EVs compared to EVs from healthy cells; such applications thus require highly sensitive and adaptable characterization tools. To address this obstacle, we designed and fabricated a novel space curvature-inspired surfaced-enhanced Raman spectroscopy (SERS) substrate and tested its capabilities using bioreactor-produced and size exclusion chromatography-purified breast cancer EVs of three different subtypes. Our findings demonstrate the platform’s ability to effectively fingerprint and efficiently classify, for the first time, three distinct subtypes of breast cancer EVs following the application of machine learning algorithms on the acquired spectra. This platform and characterization approach will enhance the viability of EVs and nanoplasmonic sensors towards clinical utility for breast cancer and many other applications to improve human health.

BACKGROUND:Prostate cancer (Pca) is the most frequently diagnosed cancer in New Zealand (NZ) men and the third leading cause of cancer deaths. Temporal changes in Pca incidence and mortality have not been reported despite changes in the Pca landscape. This study aims to analyse the temporal trends in Pca with focus on ethnic and regional variations.METHODS:The study cohort was identified from the NZ Cancer Registry and the mortality collection databases. Men who were diagnosed with Pca between 2000 and 2018 were included in the incidence analysis. Men who died from Pca between 2000 and 2015 were included in the mortality analysis. Other data collected were ethnicity and geographical information. Pca incidence and mortality were calculated as age-standardized rates using the 2001 World Health Organization population.RESULTS:A total of 58 966 men were diagnosed (incidence: 105.2 per 100 000) and 14 749 men died (mortality: 49.3 per 100 000) from Pca. When compared to European men, Māori and Asian men had significantly lower Pca incidence. Mortality rates demonstrated a steady decline, which was more prominent until 2010. Māori and Pacific men had higher mortality rates when compared to European men. In most recent years, the difference in mortality is decreasing for Māori but increasing for Pacific men. There were no regional differences in mortality.CONCLUSION:Pca incidence in NZ has fluctuated over the last 20 years, while mortality rates have shown to steadily decline. Pca mortality was shown to disproportionately affect Māori and Pacific men.

Objectives: The objectives of this study are to determine the predictors of success following extracorporeal shock-wave lithotripsy (ESWL) in a contemporary cohort at a high-volume stone center. Methods: We conducted a retrospective review all patients who underwent an elective ESWL within our institution over a 24-month period (January 2014 to December 2015). Data on patient demographics, stone variables, and inpatient treatment outcomes were evaluated. The presence of residual stone fragments larger than 4 mm on follow-up imaging was considered to be treatment failure. Using this threshold, clinically relevant variables between the treatment success and failure groups were identified. Multivariable logistic regression analyses (MVA) of clinically relevant variables were used to determine the independent factors predicting ESWL success. Results: Of 446 study eligible patients, 421 patients had complete follow-up data and were included in the analysis. Treatment was successful in 72.2% of patients in this study. Stone size, number of shocks delivered, and maximum treatment intensity were statistically different in the two groups. In a MVA where stone size, location, density, presence of ureteric stent, skin-stone distance (SSD), number of shocks, and maximum shock intensity were included, only stone size of <10 mm (odds ratio [OR] 3.4 [95% confidence interval [CI]: 1.98–5.84]) and SSD <15 cm (OR: 0.133, [95% CI: 0.027–0.65]) were the independent predictor of ESWL success. Conclusion: We have demonstrated "real world" outcomes with high-volume use of ESWL. In our experience that with diligent patient selection, ESWL remains an effective tool for the management of upper tract calculi.

Background: Prostate cancer represents a significant health burden on New Zealand men. There are increasing concerns regarding inequities in prostate cancer morbidity and mortality among the different ethnic groups in New Zealand. This study aims to assess ethnic differences in survival outcomes among men newly diagnosed with prostate cancer. Materials and methods: The analyzed cohort included 42,563 men, 40 years or older, diagnosed with prostate cancer from January 1st, 2000 to January 1st, 2016. Overall and cancer-specific survivals were estimated for the main ethnic groups in New Zealand namely: Maori (indigenous), Pacific, Asian, and European. Hazard ratio (HR) of death from prostate cancer was calculated with Fine-Gray competing risk regression, while adjusting for age, socioeconomic deprivation, year of cancer diagnosis, residential status, presence of urology service, and cancer grade at diagnosis. Results: Among all ethnic groups, Maori participants consistently had worst survival outcomes. At 15-year follow-up, the overall cumulative survival probabilities were 39.8%, 43.6%, 63.3%, and 46.5%, for Maori, Pacific, Asian and European men, respectively. In the same order, cancer-specific survivals were 62.7%, 64.3%, 79.8% and 72.0%. Maori men had 43% higher risk of dying from prostate cancer when compared to Europeans. This persisted following adjustments in the multivariable model (adjusted HR = 1.44, [95% CI: 1.29 & minus;1.61], P< 0.001). Conversely, differences in sociodemographic and cancer characteristics between Pacific and European men could explain the higher mortality risk in the former group (adjusted HR = 1.00, [95% CI: 0.84 & minus;1.19], P= 0.990). Conclusions: Significant ethnic disparities in prostate cancer survival outcomes are currently present in New Zealand. Several explanations have been proposed to account for this observation including differences in comorbidities, healthcare access and cancer grade at diagnosis. (C) 2021 Elsevier Inc. All rights reserved.