Association between dietary 3-monochloropropane-1,2-diol esters (3-MCPDE) and renal cancer in Peninsular Malaysia: exposure assessment and matched case-control study.

3-Monochloropropane-1,2-diol esters (3-MCPDE) are food contaminants commonly found in refined vegetable oils and fats, which have possible carcinogenic implications in humans. To investigate this clinically, we conducted an occurrence level analysis on eight categories of retail and cooked food commonly consumed in Malaysia. This was used to estimate the daily exposure level, through a questionnaire-based case-control study involving 77 subjects with renal cancer, with 80 matching controls. Adjusted Odds Ratio (AOR) was calculated using the multiple logistic regression model adjusted for confounding factors. A pooled estimate of total 3-MCPDE intake per day was compared between both groups, to assess exposure and disease outcome. Among the food categories analysed, vegetable fats and oils recorded the highest occurrence levels (mean: 1.91 ± 1.90 mg/kg), significantly more than all other food categories (p < .05). Risk estimation found the Chinese ethnic group to be five times more likely to develop renal cancer compared to Malays (AOR = 5.15, p = .001). However, an inverse association was observed as the 3-MCPDE exposure among the Malays (median: 0.162 ± 0.229 mg/day/person) were found to be significantly higher than the Chinese (p = .001). There was no significant difference (p = .405) in 3-MCPDE intake between the cases (median: 0.115 ± 0.137 mg/day/person) and controls (median: 0.105 ± 0.151 mg/day/person), with no association between high intake of 3-MCPDE and the development of renal cancer (OR = 1.41, 95% CI: 0.5091-2.5553). Thus, there was insufficient clinical evidence to suggest that this contaminant contributes to the development of renal malignancies in humans through dietary consumption. Further research is necessary to support these findings, which could have significant public health ramifications for the improvement of dietary practices and food safety measures.

Cardiovascular risk factors, ethnicity and infection stone are independent factors associated with reduced renal function in renal stone formers.

BACKGROUND: Recent evidence suggested the link between nephrolithiasis and renal function impairment. We aimed to determine the renal function profile and potential factors associated with reduced renal function amongst renal stone formers in multi-ethnic Asians. METHODS: We conducted a cross-sectional study involving patients undergoing percutaneous nephrolithotomy between May 2015 and December 2019. Reduced renal function was defined as having estimated glomerular filtration rate < 60 ml/min per 1.73 m2. Renal stone samples were collected and quantified using infrared spectroscopy. Potential factors associated with reduced renal function including age, ethnicity, educational level, history of diabetes, hypertension, gout, hydronephrosis, serum uric acid level, and type of renal stone were evaluated using univariable and multivariable analyses. RESULTS: A total of 1162 patients from a multi-ethnic population (Malays 67%, Chinese 19%, Indians 13% and indigenous people 1%) with median age of 57 years (Interquartile range 48-64) were enrolled in the study. Almost a third of patients were found with reduced renal function. Multivariable analysis showed that the odds of having reduced renal function increased with age, ethnicity, lower educational level, history of diabetes, hypertension, gout, bilateral hydronephrosis, elevated serum uric acid level and infection stone. CONCLUSIONS: Reduced renal function varies between ethnicities and all age groups of renal stone formers. In addition to age and ethnicity, cardiovascular risk factors including diabetes and hypertension may also need to be taken into account in managing stone patients with reduced renal function.

ELIGANT: a Phase 4, interventional, safety study of leuprorelin acetate (ELIGARD®) in Asian men with prostate cancer.

Background: The incidence and mortality rate of men with prostate cancer have been increasing in Asia. ELIGARD® is a formulation of leuprorelin acetate whose safety and efficacy have been well-established in Western regions. However, limited safety data are available for Asian populations. Methods: ELIGANT (ELIGard AsiaN sTudy) was a Phase 4, multicenter, prospective, single-arm, interventional study. Men with locally advanced or metastatic prostate cancer without concomitant chemotherapy, or another androgen receptor pathway inhibitor, were enrolled across Asia to receive ELIGARD® (22.5 mg subcutaneous depot injection) every 3 months for 15 months, with a follow-up visit at 18 months. The primary objective was to establish the safety of ELIGARD® in Asian men with hormone-dependent prostate cancer. The secondary objectives were to assess efficacy, via prostate-specific antigen (PSA) progression and testosterone levels, and health-related quality of life (HRQoL). Results: In total, 106 patients were included in the safety analysis set (SAF). The most common treatment-emergent adverse events (TEAEs) included PSA increase, cough, back pain, hot flush, anemia, and upper respiratory tract infection. TEAEs considered related to ELIGARD® were reported in 13.2% of patients (n=14), two of which were serious. In the full analysis set (FAS) (n=105), 81.2% (n=56) and 68.5% (n=61) of patients achieved a PSA reduction of ≥90% from baseline at 12 and 18 months, respectively. At 18 months, the numbers of patients with testosterone levels <20, 20-50, and >50 ng/dL were 65 (61.9%), 17 (16.2%), and two (1.9%), respectively; 20% had missing testosterone measurements. HRQoL remained stable throughout the study with minimal change from baseline at study completion. Conclusions: In conclusion, the safety profile of ELIGARD® (22.5 mg) in Asian men with hormone-dependent prostate cancer is comparable to previous studies in Western regions. Trial Registration: Clinical trial registration number NCT03035032.

Managing advanced prostate cancer in the Asia Pacific region: "Real-world" application of Advanced Prostate Cancer Consensus Conference 2019 statements.

AIM: The second Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2020) gathered insights into the real-world application in the Asia-Pacific (APAC) region of consensus statements from the 3rd Advanced Prostate Cancer Consensus Conference (APCCC 2019). METHODS: The 4-h our virtual meeting in October 2020 brought together 26 experts from 14 APAC countries to discuss APCCC 2019 recommendations. Presentations were prerecorded and viewed prior to the meeting. A postmeeting survey gathered views on current practice. RESULTS: The meeting and survey highlighted several developments since APAC APCCC 2018. Increased access and use in the region of PSMA PET/CT imaging is providing additional diagnostic and staging information for advanced prostate cancer and influencing local and systemic therapy choices. Awareness of oligometastatic disease, although not clearly defined, is increasing. Novel androgen receptor pathway antagonists are expanding treatment options. Cost and access to contemporary treatments and technologies continue to be a significant factor influencing therapeutic decisions in the region. With treatment options increasing, multidisciplinary treatment planning, shared decision making, and informed choice remain critical. A discussion on the COVID-19 pandemic highlighted challenges for diagnosis, treatment, and clinical trials and new service delivery models that will continue beyond the pandemic. CONCLUSION: APAC-specific prostate cancer research and data are important to ensure that treatment guidelines and recommendations reflect local populations and resources. Facilitated approaches to collaboration across the region such as that achieved through APAC APCCC meetings continue to be a valuable mechanism to ensure the relevance of consensus guidelines within the region.

Predicting the diagnosis of prostate cancer with a scoring system based on novel biomarkers.

OBJECTIVE: To predict prostate cancer using novel biomarker ratios and create a predictive scoring system. MATERIALS AND METHODS: Data of a total of 703 patients who consulted Urology Department of Selayang Hospital between January 2013 and December 2017 and underwent prostate biopsy were screened retrospectively. Prostate specific antigen (PSA) levels, prostate volumes (PV), neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), Prostate specific antigen density (PSAD) and histopathology were evaluated. RESULTS: Ages ranged from 43 to 89 years, divided into 2 groups as per biopsy results; positive for prostate cancer (n = 290, 41.3%) and negative for malignancy (n = 413; 58.7%). Intergroup comparative evaluations were performed. Independent variables with p < 0.001 in the univariate analysis were age, DRE, PV, NLR, PSAD. A scoring system was modelled using NLR < 0.9, PSAD > 0.4, Age > 70 and DRE. A score of 2 or more predicted prostate cancer with a Sensitivity of 83.8% and Specificity of 86.4%. CONCLUSIONS: NLR is shown to be good predictor for prostate cancer its usage in this scoring system affords more disease specificity as compared to PSA alone.

Does alkalinised urine reduce the rate of encrustation in patients with ureteric stents? A randomised controlled study.

PURPOSE: Stent encrustation is not uncommonly encountered with a high number of ureteric stents. The exact pathophysiology is not well understood. Therefore, we investigated the relationship between the use of sodium citrate and likelihood of stent encrustation. METHODS: This prospective, randomised, intervention study was conducted between October 2018 and October 2019 in a tertiary hospital. Overall, 115 patients with ureteral stents that were inserted after lithotripsy surgeries were recruited. The study subjects were randomised into two groups: one group was administered sodium citrate (Utix sachets) three times per day until stent removal (intervention group), and the second group was not administered Utix sachets (control group). Stents were removed after 1 month and inspected under macroscopic visualisation from the proximal to distal end for any crystallisation; a second inspection was done with a 60 × magnification lens. Any crystallisation observed was considered to be encrustation. RESULTS: Patients who had Utix sachets post-insertion of a ureteric stent constituted 50.4% of the study cohort. The rate of encrustation in the control group was 52.6%. In the intervention group, the rate of encrustation was 46.6%. The difference was not statistically significant with the chi-squared test (p value, 0.514). CONCLUSION: Alkaline citrate medications had no significant effect on stent encrustation rate. More studies are needed to elucidate different agents and their roles in reducing stent encrustation as it incurs high morbidity.

Prostate cancer in multi-ethnic Asian men: Real-world experience in the Malaysia Prostate Cancer (M-CaP) Study.

Prostate cancer is the third most common cancer in Malaysia with the lifetime risk of 1 in 117 men. Here, we initiated a longitudinal Malaysia Prostate Cancer (M-CaP) Study to investigate the clinical and tumour characteristics, treatment patterns as well as disease outcomes of multi-ethnic Asian men at real-world setting. The M-CaP database consisted of 1839 new patients with prostate cancer diagnosed between 2016 and 2018 from nine public urology referral centres across Malaysia. Basic demographic and clinical parameters, tumour characteristics, primary treatment, follow-up and vital status data were retrieved prospectively from the hospital-based patients' case notes or electronic medical records. Primary endpoints were overall survival (OS) and biochemical progression-free survival (bPFS). The median age at diagnosis of M-CaP patients was 70 years (interquartile range, IQR 65-75). Majority of patients were Chinese (831, 45.2%), followed by Malays (704, 38.3%), Indians (124, 6.7%) and other races (181, 9.8%). The median follow-up for all patients was 23.5 months (IQR 15.9-33.6). Although 58.1% presented with late-stage cancer, we observed ethnic and geographic disparities in late-stage prostate cancer diagnosis. Curative radiotherapy and primary androgen deprivation therapy were the most common treatment for stage III and stage IV diseases, respectively. The median OS and bPFS of stage IV patients were 40.1 months and 19.2 months (95% CI 17.6-20.8), respectively. Late stage at presentation remains a challenge in multi-ethnic Asian men. Early detection is imperative to improve treatment outcome and survival of patients with prostate cancer.

Recent trend of androgen deprivation therapy in newly diagnosed prostate cancer patients: Comparing between high- and middle-income Asian countries.

The number of newly diagnosed prostate cancer cases varies across Asia, with higher mortality-to-incidence ratio reported in developing nations. Androgen deprivation therapy (ADT), alone or in combination, remains the mainstay of first-line treatment for advanced prostate cancer. Key findings of extensive research and randomized controlled trials have shaped current clinical practice and influenced clinical guideline recommendations. We describe here the recent trend of ADT in newly diagnosed prostate cancer for Asia focusing on Japan (high-income country) and Malaysia (middle-income country) based on the Asian Prostate Cancer (A-CaP) Study. The combination of radiotherapy and ADT or ADT alone was common in patients with intermediate-to-high risk localized and locally advanced disease. For metastatic prostate cancer, maximum androgen blockade (gonadotrophin-releasing hormone [GnRH] agonist/antagonist plus antiandrogen) was prevalent among the Japanese patients while primary ADT alone with GnRH agonist/antagonist was widely practiced in the Malaysian cohort. Upfront combined therapy (ADT plus docetaxel or androgen receptor pathway inhibitor) has significantly improved the outcomes of patients with metastatic castration-naïve prostate cancer. Its application, however, remains low in our cohorts due to patients' financial capacity and national health insurance coverage. Early detection remains the cornerstone in prostate cancer control to improve treatment outcome and patient survival.

Modified J-CAPRA scoring system in predicting treatment outcomes of metastatic prostate cancer patients undergoing androgen deprivation therapy.

The J-CAPRA score is an assessment tool which stratifies risk and predicts outcome of primary androgen deprivation therapy (ADT) using prostate-specific antigen, Gleason score, and clinical TNM staging. Here, we aimed to assess the generalisability of this tool in multi-ethnic Asians. Performance of J-CAPRA was evaluated in 782 Malaysian and 16,946 Japanese patients undergoing ADT from the Malaysian Study Group of Prostate Cancer (M-CaP) and Japan Study Group of Prostate Cancer (J-CaP) databases, respectively. Using the original J-CAPRA, 69.6% metastatic (M1) cases without T and/or N staging were stratified as intermediate-risk disease in the M-CaP database. To address this, we first omitted clinical T and N stage variables, and calculated the score on a 0-8 scale in the modified J-CAPRA scoring system for M1 patients. Notably, treatment decisions of M1 cases were not directly affected by both T and N staging. The J-CAPRA score threshold was adjusted for intermediate (modified J-CAPRA score 3-5) and high-risk (modified J-CAPRA score ≥6) groups in M1 patients. Using J-CaP database, validation analysis showed that overall survival, prostate cancer-specific survival, and progression-free survival of modified intermediate and high-risk groups were comparable to those of original J-CAPRA (p > 0.05) with Cohen's coefficient of 0.65. Around 88% M1 cases from M-CaP database were reclassified into high-risk category. Modified J-CAPRA scoring system is instrumental in risk assessment and treatment outcome prediction for M1 patients without T and/or N staging.

Management of advanced prostate cancer in a middle-income country: real-world consideration of the Advanced Prostate Cancer Consensus Conference 2017.

OBJECTIVE: To examine the results of the Malaysian Advanced Prostate Cancer Consensus Conference (MyAPCCC) 2018, held for assessing the generalizability of consensus reached at the Advanced Prostate Cancer Consensus Conference (APCCC 2017) to Malaysia, a middle-income country. METHODS: Six key sections were chosen: (1) high-risk localized and locally advanced prostate cancer, (2) oligometastatic prostate cancer, (3) castration-naïve prostate cancer, (4) castrate resistant prostate cancer, (5) use of osteoclast-targeted therapy and (6) global access to prostate cancer drugs. There were 101 consensus questions, consisting of 91 questions from APCCC 2017 and 10 new questions from MyAPCCC 2018, selected and modified by the steering committee; of which, 23 questions were assessed in both ideal world and real-world settings. A panel of 22 experts, comprising of 11 urologists and 11 oncologists, voted on 101 predefined questions anonymously. Final voting results were compared with the APCCC 2017 outcomes. RESULTS: Most voting results from the MyAPCCC 2018 were consistent with the APCCC 2017 outcomes. No consensus was achieved for controversial topics with little level I evidence, such as management of oligometastatic disease. No consensus was reached on using high-cost drugs in castration-naïve or castration-resistant metastatic prostate cancer in real-world settings. All panellists recommended using generic drugs when available. CONCLUSIONS: The MyAPCCC 2018 voting results reflect the management of advanced prostate cancer in a middle-income country in a real-world setting. These results may serve as a guide for local clinical practices and highlight the financial challenges in modern healthcare.

A Novel Calculator for Estimating Prostate Volume in Daily Urology Services.

OBJECTIVES: To develop a simple prostate volume (PV) calculator that can aid in managing patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement at daily urology services in developing Asian countries. MATERIALS AND METHODS: We conducted a cross-sectional study of men aged above 40 years with no history of prostate cancer, prostate surgery, or 5α-reductase inhibitor treatment. Serum prostate-specific antigen (PSA) and total PV were measured in each subject. Potential sociodemographic and clinical variables including age, weight, comorbidities, and International Prostate Symptom Score (IPSS) were collected. Of 1034 subjects, 837 were used in building the PV calculator using regression analysis. The remaining 1/5 (n = 197) was used for model validation. RESULTS: There were 1034 multiethnic Asian men (Chinese 52.9%, Malay 35.4%, and Indian 11.7%) with mean age of 60 ± 7.6 years. Average PV was 29.4 ± 13.0 mL while the overall mean of PSA was 1.7 ± 1.7 ng/mL. We identified age, IPSS, weight, and PSA (all P <.05) in the PV regression model. Using the validation set, the coefficient of determination (R2) of this PV calculator was 0.47 where PV = 20.6 + (age - 60) × 0.1 + (IPSS score) × 0.1 + (Weight - 70) × 0.3 + (history of alpha-blocker treatment for LUTS) × 9.6 + PSA × 3.7. The area under curve of this model in predicting PV above 30 mL and 40 mL were 0.82 (95% confidence interval, 0.75-0.88) and 0.91 (95% confidence interval, 0.87-0.96), respectively. CONCLUSION: We develop a PV calculator that is simple and accurate to be used in routine clinical consultation for patients with LUTS. A separate study is important to confirm and to validate the findings in other populations.

A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer.

OBJECTIVE: This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed. RESULTS: The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3-4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively. CONCLUSION: In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.

Cardiovascular Risk Factors and Ethnicity Are Independent Factors Associated with Lower Urinary Tract Symptoms.

OBJECTIVES: To determine the lower urinary tract symptoms (LUTS) profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in a multiethnic Asian setting. MATERIALS AND METHODS: We conducted a cross-sectional study of 1021 men aged 40-79 years with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The severity of LUTS was assessed using the International Prostate Symptom Score (IPSS). Potential factors associated with LUTS including age, ethnicity, education, history of hypertension, diabetes and hypercholesterolemia, height, weight, and prostate volume were evaluated using univariable and multivariable analyses. RESULTS: There were 506 (50%) men found to have moderate-to-severe LUTS attaining an IPSS above 7. Overall, nocturia (45.5%) was the most frequently reported symptom. Multivariable analysis showed that age, ethnicity, prostate volume and history of hypertension and hypercholesterolemia were independent factors associated with severity of LUTS (p < 0.05). Considering individual lower urinary tract symptoms, we found a strong association of storage symptom with history of hypertension and hypercholesterolemia. Malay men were significantly bothered by post micturition symptom compared to their Chinese and Indian counterparts. Stratified analyses of LUTS demonstrated a mutually exclusive cardiovascular risk factors profile defined by ethnicity. CONCLUSION: Severity of LUTS varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity and cardiovascular risk factors including hypertension and hypercholesterolemia may also need to be taken into account in managing men with LUTS.

Ethnicity is an independent determinant of age-specific PSA level: findings from a multiethnic Asian setting.

OBJECTIVES: To study the baseline PSA profile and determine the factors influencing the PSA levels within a multiethnic Asian setting. MATERIALS AND METHODS: We conducted a cross-sectional study of 1054 men with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The serum PSA concentration of each subject was assayed. Potential factors associated with PSA level including age, ethnicity, height, weight, family history of prostate cancer, lower urinary tract voiding symptoms (LUTS), prostate volume and digital rectal examination (DRE) were evaluated using univariable and multivariable analysis. RESULTS: There were 38 men (3.6%) found to have a PSA level above 4 ng/ml and 1016 (96.4%) with a healthy PSA (≤4 ng/ml). The median PSA level of Malay, Chinese and Indian men was 1.00 ng/ml, 1.16 ng/ml and 0.83 ng/ml, respectively. Indians had a relatively lower median PSA level and prostate volume than Malays and Chinese, who shared a comparable median PSA value across all 10-years age groups. The PSA density was fairly similar amongst all ethnicities. Further analysis showed that ethnicity, weight and prostate volume were independent factors associated with age specific PSA level in the multivariable analysis (p<0.05). CONCLUSION: These findings support the concept that the baseline PSA level varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity may also need to be taken into account when investigating serum PSA concentrations in the multiethnic Asian population.

Prostate cancer screening perspective, Malaysia.

The incidence of prostate cancer in Malaysia is still low compared to the west. This may be due to a true low incidence or lower detection rates. Prostate Awareness Campaigns are held on a yearly basis to educate and encourage males over the age of 50 years to have their prostate examined. Such a campaign was organized in 2005 at the national level involving 12 district hospitals. A total of 2770 participants attended the campaign. 38.7% had no urinary symptoms and attended out of curiosity. Among the symptomatic patients, nocturia was the most bothersome in the majority. 84.6% of the participants also had some degree of erectile dysfunction based on the IIEF questionnaire. 10.4% of participants had a PSA > 4 ng/mL. Malay participants had the highest mean PSA level (2.32 ng/mL) and Indian participants the lowest (1.30 ng/mL). 408 participants were called back for biopsy but only 183 agreed to the biopsy. 30 cancers were detected. At present Malaysia will benefit most by continuing to conduct these awareness programmes to educate the public on prostate disease and hopefully in future patients will be less reluctant to have prostate biopsies taken when indicated.