Controversies in terminology associated with management of BCG-unresponsive NMIBC in Asia-Pacific.

OBJECTIVES: Examine the understanding of terminologies and management patterns of bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) in six territories in Asia-Pacific. METHODS: This study involved two phases: (1) a survey with 32 urologists and 7 medical oncologists (MOs) and (2) a factorial experiment and in-depth interviews with 23 urologists and 2 MOs. All clinicians had ≥8 years' experience managing NMIBC patients in Australia, Hong Kong, Japan, South Korea, Singapore, and Taiwan. Data from Phase 1 were summarized using descriptive statistics; content and thematic analyses applied in Phase 2. RESULTS: In phase 1, 35% of clinicians defined BCG-unresponsive as BCG-refractory, -relapse and -resistant, 6% defined it as BCG-refractory and -relapse; 22% classified BCG-failure as BCG-refractory, -relapse, -resistant, and when muscle-invasive bladder cancer is detected. If eligible and willing, 50% (interquartile range [IQR], 50%-80%) of BCG-unresponsive patients would undergo radical cystectomy (RC), and 50% (IQR 20%-50%) of RC-eligible patients would receive bladder-sparing treatment or surveillance. In phase 2, we found that 32%, 88%, and 48% of clinicians, respectively, used "BCG-unresponsive," "BCG-refractory," and "BCG-relapse" in clinical practice but with no consistent interpretation of the terms. Compared with EAU definitions, 8%-60% of clinicians appropriately classified 9 tumor types that are persistent or recurrent after adequate BCG. Fifty percent of clinicians mentioned a lack of bladder-preserving treatment that outperforms RC in quality of life as a reason to retreat BCG-unresponsive patients with BCG. CONCLUSIONS: Our study revealed varied understanding and application of BCG-unresponsive terminologies in practice. There is a need for a uniform and simple definition of BCG-unresponsive disease in Asia-Pacific.

Risk stratification and management of non-muscle-invasive bladder cancer: A physician survey in six Asia-Pacific territories.

OBJECTIVES: Multiple clinical practice guidelines, conflicting evidence, and physician perceptions result in variations in risk stratification among patients with non-muscle-invasive bladder cancer (NMIBC). This study aims to describe the extent of this variation and its impact on management approaches in the Asia-Pacific region. METHODS: We conducted a cross-sectional survey involving 32 urologists and seven medical oncologists with ≥8 years of experience managing early-stage bladder cancer patients across Australia, Hong Kong, Japan, South Korea, Singapore, and Taiwan. The physicians completed an anonymous questionnaire that assessed their risk stratification and respective management approaches, based on 19 NMIBC characteristics. For each NMIBC characteristic, they were required to select one risk group, and their most preferred management approach. RESULTS: Our results demonstrated a higher consensus on risk classification versus management approaches. More than 50% of the respondents agreed on the risk classification of all NMIBC characteristics, but 42% or fewer chose the same treatment option as their preferred choice for all but two characteristics-existence of variant histology (55%) and persistent high-grade T1 disease on repeat resection (52%). Across territories, there was the greatest variation in preferred treatment options (i.e., no treatment, intravesical chemotherapy, or Bacillus Calmette-Guérin [BCG] treatment) for intermediate-risk patients and the highest consensus on the treatment of very high-risk patients, namely radical cystectomy. CONCLUSIONS: Our study revealed considerable variation in risk stratification and management of NMIBC in the region. It is critical to develop practical algorithms to facilitate the recognition of NMIBC and standardize the treatment of NMIBC patients.

Consensus statements on the management of clinically localized prostate cancer from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology.

OBJECTIVE: To formulate consensus statements to facilitate physician management strategies for patients with clinically localized prostate cancer (PCa) in Hong Kong by jointly convening a panel of 12 experts from the two local professional organizations representing PCa specialists, who had previously established consensus statements on the management of metastatic PCa for the locality. METHODS: Through a series of meetings, the panellists discussed their clinical experience and the published evidence regarding various areas of the management of localized PCa, then drafted consensus statements. At the final meeting, each drafted statement was voted on by every panellist based on its practicability of recommendation in the locality. RESULTS: A total of 76 consensus statements were ultimately accepted and established by panel voting. CONCLUSION: Derived from the recent evidence and major overseas guidelines, along with local clinical experience and practicability, the consensus statements were aimed to serve as a practical reference for physicians in Hong Kong for the management of localized PCa.

Consensus statements on the management of metastatic prostate cancer from the Hong Kong Urological Association and Hong Kong Society of Uro-Oncology.

To establish a set of consensus statements to facilitate physician management strategies for patients with metastatic prostate cancer (mPCa) in Hong Kong. A local expert consensus was organized jointly by the two main professional organizations representing prostate cancer specialists in Hong Kong. A total of 12 experts were included in the consensus panel. Six of the most crucial and relevant areas of debate regarding the management of mPCa were identified. With the use of a modified Delphi method, several panel meetings were held for the members to discuss their clinical experience and the published literature relevant to the areas of debate. At the final meeting, each drafted statement was voted on by every member based on its practicability of recommendation in the locality. After the panel voting, a total of 45 consensus statements regarding the management of mPCa were ultimately accepted and established. The consensus statements were primarily derived from the latest clinical evidence and major overseas guidelines, with the consideration of local clinical experience and practicability. These are considered applicable recommendations for Hong Kong physicians for the management of mPCa patients.

Androgen deprivation therapy, diabetes and poor physical performance status increase fracture risk in Chinese men treated for prostate cancer.

We investigated the fracture risk after androgen deprivation therapy (ADT) for prostate cancer in the Chinese population. All Chinese prostate cancer patients who were treated primarily by radical prostatectomy or radiotherapy, with or without further ADT, from year 2000 to 2009 were reviewed. We compared the fracture risk in patients who were given ADT (ADT group) with those who were not given any ADT (non-ADT group). Potential risk factors including age, diabetes mellitus, hypertension, hyperlipidemia, ischemic heart disease and performance status were reviewed. The fracture risk was analyzed with Kaplan-Meier and multivariate Cox regression analyses. Our cohort consisted of 200 patients in the non-ADT group and 252 patients in the ADT group. The ADT group was shown to have higher fracture risk (p = 0.036) upon Kaplan-Meier analysis. Upon multivariate Cox regression analyses, diabetes mellitus (HR 4.39, 95% CI 1.08-17.83, p = 0.039), poor performance status (HR 3.14, 95% CI 1.24-8.00, p = 0.016) and the use of ADT (HR 4.89, 95% CI 1.03-23.17, p = 0.045) were associated with increased fracture risk. In conclusion, the fracture risk should be considered while deciding on ADT in Chinese men, especially in diabetic patients with poor performance status.

Risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population living in Hong Kong.

OBJECTIVE: Previous reports on the risk of stroke after androgen deprivation therapy for prostate cancer were largely based on Caucasians. We investigated the risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population. METHODS: All Chinese prostate cancer patients who were treated primarily with radical prostatectomy or radiotherapy, with (androgen deprivation therapy group) or without (non-androgen deprivation therapy group) further androgen deprivation therapy, at our hospital from year 2000-09 were reviewed. Potential risk factors of ischemic stroke including age, baseline prostate-specific antigen, Gleason score, clinical T stage, hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease, history of stroke, use of androgen deprivation therapy and duration of androgen deprivation therapy were reviewed. The risk of ischemic stroke after androgen deprivation therapy was analyzed with Kaplan-Meier and multivariate Cox regression analyses. RESULTS: A total of 452 patients were included, consisting of 200 patients in the non-androgen deprivation therapy group and 252 patients in the androgen deprivation therapy group. The androgen deprivation therapy group appeared to have increased risk of ischemic stroke when compared with the non-androgen deprivation therapy group (P = 0.063) upon Kaplan-Meier analysis. Upon multivariate Cox regression analyses, older age (hazard ratio 1.13, 95% confidence interval 1.04-1.22, P = 0.003), hyperlipidemia (hazard ratio 4.61, 95% confidence interval 2.01-10.54, P < 0.001) and the use of androgen deprivation therapy (hazard ratio 3.32, 95% confidence interval 1.14-9.67, P = 0.028) were associated with increased risk of ischemic stroke. CONCLUSIONS: There was increased risk of ischemic stroke after androgen deprivation therapy for prostate cancer in the Chinese population. The risk of ischemic stroke should be considered while deciding on androgen deprivation therapy, especially in older patients with known history of hyperlipidemia.

Prostate cancer management in the era of COVID-19: Recommendations from the Hong Kong Urological Association and Hong Kong Society of Uro-oncology.

AIM: In response to the fast-developing coronavirus disease 2019 (COVID-19) pandemic, special arrangement and coordination are urgently required in the interdisciplinary care of patients across different medical specialties. This article provides recommendations on the management of different stages of localized or metastatic prostate cancer (PC) amid this pandemic. METHODS: The Hong Kong Urological Association and Hong Kong Society of Uro-oncology formed a joint discussion panel, which consisted of six urologists and six clinical oncologists with extensive experience in the public and private sectors. Following an evidence-based approach, the latest relevant publications were searched and reviewed, before proceeding to a structured discussion of relevant clinical issues. RESULTS: The joint panel provided recommendations for PC management during the pandemic, in terms of general considerations, diagnostic procedures, different disease stages, treatment modules, patient support, and interdisciplinary collaboration. The overall goal was to minimize the risk of infection while avoiding unnecessary delays and compromises in management outcomes. Practical issues during the pandemic were addressed such as the use of invasive diagnostic procedures, robotic-assisted laparoscopic prostatectomy, hypofractionated radiotherapy, and prolonged androgen deprivation therapy. The recommendations were explicated in the context of Hong Kong, a highly populated international city, in relation to the latest international guidelines and evidence. CONCLUSION: A range of recommendations on the management of PC patients during the COVID-19 pandemic was developed. Urologists, oncologists, and physicians treating PC patients may refer to them as practical guidance.

Consensus statements on the management of metastatic renal cell carcinoma from the Hong Kong Urological Association and the Hong Kong Society of Uro-Oncology 2019.

BACKGROUND: To establish a set of consensus statements for the management of metastatic renal cell carcinoma, a total of 12 urologists and clinical oncologists from two professional associations in Hong Kong formed an expert consensus panel. METHODS: Through a series of meetings and using the modified Delphi method, the panelists presented recent evidence, discussed clinical experiences, and drafted consensus statements on several areas of focus regarding the management of metastatic renal cell carcinoma. Each statement was eventually voted upon by every panelist based on the practicability of recommendation. RESULTS: A total of 46 consensus statements were ultimately accepted and established by panel voting. CONCLUSIONS: Derived from recent evidence and expert insights, these consensus statements were aimed at providing practical guidance to optimize metastatic renal cell carcinoma management and promote a higher standard of clinical care.

Hong Kong Urological Association-Hong Kong Society of Uro-Oncology consensus statements on the management of advanced prostate cancer-2019 Updates.

BACKGROUND: To update the Hong Kong Urological Association-Hong Kong Society of Uro-Oncology consensus statements on the management of advanced prostate cancer, the same panelists as in the previous consensus panel held a series of meetings to discuss updated clinical evidence and experiences. METHODS: The previous consensus statements were retained, deleted, or revised, and new statements were added. At the final meeting, all statements were reviewed and amended as appropriate, followed by panel voting. RESULTS: There were significant changes and additions to the previous consensus statements, primarily driven by the advances in androgen receptor signaling inhibitors, treatment sequencing in metastatic castration-resistant prostate cancer, and increasing recognition of oligometastatic prostate cancer since the introduction of prostate-specific membrane antigen positron emission tomography. In this update, a total of 59 consensus statements were accepted and established. CONCLUSIONS: The consensus panel updated consensus statements on the management of advanced prostate cancer, aiming to allow physicians in the region to keep abreast of the recent evidence on optimal clinical practices.

Immunotherapy for urothelial carcinoma: Metastatic disease and beyond.

For advanced and metastatic urothelial carcinomas (UCs), platinum (preferably cisplatin)-based chemotherapy has been the standard treatment for many years. However, many patients are ineligible for cisplatin-based chemotherapy because of poor performance status and/or other age-related conditions. At the other end of the spectrum, patients with localized non-muscle-invasive bladder cancer who are unresponsive to intravesical Bacillus Calmette-Guérin (BCG) treatment often face radical cystectomy as the only option. In recent years, the application of immunotherapy in the form of immune-checkpoint inhibitors has provided viable alternatives in the second-line postplatinum and first-line cisplatin-ineligible settings. Recent and ongoing clinical trials are also assessing the safety and efficacy of immunotherapy for neoadjuvant and adjuvant uses before/after cystectomy, for BCG-unresponsive cases, and for combination treatments that include the newer indoleamine 2,3-dioxygenase-1 inhibitors and/or BCG. This review summarizes recent developments in immunotherapy for UCs.

An International Collaborative Consensus Statement on En Bloc Resection of Bladder Tumour Incorporating Two Systematic Reviews, a Two-round Delphi Survey, and a Consensus Meeting.

BACKGROUND: There has been increasing interest in en bloc resection of bladder tumour (ERBT) as an oncologically noninferior alternative to transurethral resection of bladder tumour (TURBT) with fewer complications and better histology specimens. However, there is a lack of robust randomised controlled trial (RCT) data for making recommendations. OBJECTIVE: We aimed to develop a consensus statement to standardise various aspects of ERBT for clinical practice and to guide future research. DESIGN, SETTING, AND PARTICIPANTS: We developed the consensus statement on ERBT using a modified Delphi method. First, two systematic reviews were performed to investigate the clinical effectiveness of ERBT versus TURBT (effectiveness review) and to identify areas of uncertainty in ERBT (uncertainties review). Next, 200 health care professionals (urologists, oncologists, and pathologists) with experience in ERBT were invited to complete a two-round Delphi survey. Finally, a 16-member consensus panel meeting was held to review, discuss, and re-vote on the statements as appropriate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Meta-analyses were performed for RCT data in the effectiveness review. Consensus statements were developed from the uncertainties review. Consensus was defined as follows: (1) ≥70% scoring a statement 7-9 and ≤15% scoring the statement 1-3 (consensus agree), or (2) ≥70% scoring a statement 1-3 and ≤15% scoring the statement 7-9 (consensus disagree). RESULTS AND LIMITATIONS: A total of 10 RCTs were identified upon systematic review. ERBT had a shorter irrigation time (mean difference -7.24 h, 95% confidence interval [CI] -9.29 to -5.20, I2 = 85%, p < 0.001) and a lower rate of bladder perforation (risk ratio 0.30, 95% CI 0.11-0.83, I2 = 1%, p = 0.02) than TURBT, both with moderate certainty of evidence. There were no significant differences in recurrences at 0-12, 13-24, or 25-36 mo (all very low certainty of evidence). A total of 103 statements were developed, of which 99 reached a consensus. A summary of statements is as follows: ERBT should always be considered for treating non-muscle-invasive bladder cancer; ERBT should be considered feasible even for bladder tumours larger than 3 cm; number and location of bladder tumours are not major limitations in performing ERBT; the planned circumferential margin should be at least 5 mm from any visible bladder tumour; after ERBT, additional biopsy of the tumour edge or tumour base should not be performed routinely; for the ERBT specimen, T1 substage, and circumferential and deep resection margins must be assessed; it is safe to give a single dose of immediate intravesical chemotherapy, perform second-look transurethral resection, and give intravesical bacillus Calmette-Guérin (BCG) therapy after ERBT; and in studies of ERBT, both per-patient and -tumour analysis should be performed for different outcomes as appropriate. Important outcomes for future ERBT studies were also identified. A limitation is that as consensus statements are brief, concise and binary in nature, areas of uncertainty that are complex in nature may not be addressed adequately. CONCLUSIONS: We have provided the most comprehensive review of the evidence base to date using a meta-analysis where appropriate and applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and mobilised the international urology community to develop a consensus statement on ERBT using transparent and robust methods. The consensus statement will provide interim guidance for health care professionals who practice ERBT and inform researchers regarding ERBT-related studies in the future. PATIENT SUMMARY: En bloc resection of bladder tumour (ERBT) is a surgical technique aiming to resect a bladder tumour in one piece. We included an international panel of experts to agree on the best practice of ERBT, and this will provide guidance to clinicians and researchers in the future.

Management of advanced prostate cancer in Hong Kong: Insights from an APCCC-Derived survey.

AIM: The 2017 Advanced Prostate Cancer Consensus Conference (APCCC) convened an international multidisciplinary panel to vote on controversial issues in the management of advanced prostate cancer (APC). We aimed to compare their conclusions with the opinions of local specialists and explore the practicability of international recommendations in the healthcare setting in Hong Kong. METHODS: Urologists and clinical oncologists practicing in Hong Kong were invited to complete a survey based on the original APCCC 2017 questionnaire and recently published trials in APC. A joint committee of expert key opinion leaders was convened to discuss and analyze the voting differences between local specialists and the APCCC 2017 panel. RESULTS: The respondents constituted 21% (28/132) of registered urologists and 21% (31/146) of clinical oncologists in Hong Kong. Discrepancies in three key areas were identified as being the most timely for this analysis: (a) management of metastatic hormone-sensitive/naïve prostate cancer; (b) management of metastatic castration-resistant prostate cancer; and (c) treatment monitoring and initiation of androgen-deprivation therapy. Fears of toxicity and intolerance among patients and physicians (especially urologists) may be driving the relative underuse of chemotherapy in multiple APC patient groups in Hong Kong. Local patients can face long wait times and limited access to contemporary imaging modalities compared with other developed countries. CONCLUSION: Increased collaborative efforts by urologists and clinical oncologists could ensure that patients gain wider access to the latest diagnostic, treatment and monitoring modalities for APC in Hong Kong.

Chemohormonal therapy for metastatic hormone-sensitive prostate cancer: An Asian perspective.

The treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has been rapidly evolving. In the past, the use of chemotherapy was reserved for metastatic prostate cancer patients who developed castration resistance. Subsequently, there were three well-designed randomized controlled trials investigating the use of chemotherapy together with androgen deprivation therapy as the first-line treatment for metastatic hormone-sensitive prostate cancer. The GETUG-AFU 15 study was a negative trial, but the subsequent CHAARTED and STAMPEDE studies demonstrated magnificent survival benefit in the mHSPC setting. Since then, the use of chemohormonal therapy has become accepted and popularized worldwide. However, these results were largely based on Caucasians. Because of the genetic and physiological differences between different ethnicities, there has been concern over whether these results could be readily translated to the Asian population. Would Asians in general have a different tolerability towards chemohormonal therapy? Would prostate cancer in the Asian population have a different biological response towards chemohormonal therapy? In this review paper, we will present the available data regarding the use of chemohormonal therapy for mHSPC and discuss their implications from an Asian perspective.

Risk of new-onset diabetes after androgen deprivation therapy for prostate cancer in the Asian population.

BACKGROUND: The associations of androgen deprivation therapy (ADT) with its adverse events in the Asian population remained largely unknown. We investigated the risk of new-onset diabetes mellitus (DM) after ADT for prostate cancer in the Asian population. METHODS: All prostate cancer patients who were treated primarily with radical prostatectomy or radiotherapy, with or without further ADT from 2000 to 2009 were reviewed. Clinical parameters including age, clinical T stage, Gleason score, hypertension, dyslipidemia, impaired fasting glucose, ischemic heart disease, history of stroke, new-onset DM, follow-up duration, form and duration of ADT were reviewed. The risk of DM after ADT was analyzed with Kaplan-Meier method and multivariate Cox regression analysis. RESULTS: A total of 388 patients were included, consisting of 169 patients in the non-ADT group and 219 patients in the ADT group. Upon Kaplan-Meier analysis, the ADT group had a higher risk of new-onset DM (P = 0.011). Upon multivariate Cox regression analysis, dyslipidemia (HR 2.32, 95% CI 1.07-5.00, P = 0.032), impaired fasting glucose (HR 5.92, 95% CI 1. 2.27-15.45, P < 0.001) and the use of ADT in the form of GnRH agonist (HR 3.34, 95% CI 1.19-9.39, P = 0.022) and bilateral orchiectomy (HR 6.49, 95% CI 1.48-28.55, P = 0.013) were associated with increased risk of new-onset DM. CONCLUSIONS: There was increased risk of new-onset DM after ADT for prostate cancer in the Asian population. Regular screening of DM can be considered after the initiation of ADT, especially in patients with known history of dyslipidemia and impaired fasting glucose.