Managing advanced prostate cancer in the Asia Pacific region: “Real‐world” application of Advanced Prostate Cancer Consensus Conference 2019 statements

Abstract 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.


INTRODUCTION
The second Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2020) was convened in October 2020 following the 2019 Advanced Prostate Cancer Consensus Conference (APCCC 2019). 1 APCCC recommendations take an "ideal-world" perspective with no resource constraints and where patients reflect trial populations. In the Asia-Pacific (APAC) region, populations often differ from "idealized" clinical trial populations, and resources vary. APAC APCCC meetings consider the real-world application of international consensus statements for the APAC region.
Advanced prostate cancer is a significant issue for the APAC region.
Patients present with advanced disease at much higher rates than in the United States (50% vs. 10%), 2,3 driven by differences in ethnicity and access to screening, testing, and treatment.
Access to and reimbursement of imaging modalities, radiation therapy, systemic therapies, and genomic testing varies in the APAC region ( Figure 1A-D). Some newer systemic therapies are more available in generic form in some APAC countries. The increased likelihood of systemic treatment toxicities among some Asian populations 4,5 also influences management.

METHODS
APAC APCCC 2020 brought together 26 advanced prostate cancer experts from 14 APAC countries (
While the use of PSMA PET/CT is increasing in the APAC region, access and reimbursement varies ( Figure 1A)

Management of the primary tumor in metastatic disease
APCCC 2019 reported strong consensus (98%) for overall survival benefit of local treatment of the primary tumor in low-volume/low-burden M1 disease.
Radiation therapy access in the APAC region ( Figure 1C) influences choice of prostate-directed treatment in metastatic disease. In some low-and middle-income countries, lack of access to high-quality radiation therapy preferences surgery over radiation therapy, particularly F I G U R E 1 Access, approval, and reimbursement of technologies and treatments in the APAC region (n = 26). a (A) Imaging technologies, (B) systemic therapies, (C) radiation therapy, and (D) genetic testing. Abbreviations: CT, computed tomography; Lu, Lutetium; MRI, magnetic resonance imaging; PET, positron emission tomography; PSMA, prostate-specific membrane antigen; RA, radium. a Question was asked based on availability in each panelist's country, but some responses suggest that panelists replied on the basis of availability at their institution TA B L E 1 APAC APCCC 2020 panelists and survey respondents: disciplines and countries (n = 26)

Urology
Uro-oncology Medical oncology APAC APCCC 2020 panelists agreed with radiation therapy use in patients with low-burden/low-volume M1 disease, noting that the use of surgery should be restricted to clinical trials. The heterogeneity of radiation therapy mode, dose, and fractionation was discussed, with a preference for fewer fractions of higher dose radiation or SBRT (where available) to limit hospital visits, particularly during the COVID-19 pandemic. Views differed on the role of SBRT in high-volume tumors with some panelists concerned about the risk of normal tissue toxicity and justification for palliative SBRT use.

3.3
Management of newly diagnosed mHSPC, including oligometastatic disease Management of mHSPC for the need to distinguish de novo treatment-naïve (synchronous) oligometastatic prostate cancer from oligometastatic prostate cancer recurring after an initial diagnosis of M0 disease (metachronous metastases). There was also consensus that, in untreated de novo oligometastatic prostate cancer, it is important to distinguish lymph node-only disease (including distant lymph node metastases) from disease that includes metastatic lesions at other sites (81% of 26 panelists).
APAC APCCC 2020 panelists discussed the difficulty of obtaining a differential diagnosis between true oligometastatic disease and metastatic disease that is not yet evident, and the impact of this on decision making about local prostate-directed treatment. It was suggested that including time since diagnosis in the definition of oligometastatic disease can increase confidence in identifying disease that may be amendable to radical therapy, with time allowing subclinical metastases to become evident.
APAC APCCC 2020 panelists discussed the use of treatment to the primary/metastases to manage symptoms, improve quality of life, and slow disease progression in patients with low metastatic burden.
Data from STAMPEDE were referenced, showing that local prostatedirected treatment in metastatic disease affects progression-free and overall survival but not metastasis. 8 In the subgroup analysis, overall survival advantage was observed in patients with low-volume metastatic disease.    Panelists reflected on access and cost in the APAC region of sequencing, genetic testing, and access to biomarker-based therapies, such as olaparib. It was suggested that biomarker testing is lim-ited to patients whose disease progresses after multiple treatment lines.

Managing prostate cancer in a pandemic
APAC APCCC 2020 included discussion about the impact of COVID-19 on prostate cancer clinical care and research in the region. Concern has been raised about the impact of the pandemic on cancer diagnosis and treatment, due to diversion of resources for pandemic and public concern about accessing health services. 16,17 Clinical trial activity has also been affected, with some clinical trials suspended. 18,19 APAC APCCC panelists highlighted a range of impacts of COVID-19 on prostate cancer management (Table 3) including: • fewer patients presenting for diagnosis, follow-up, and support, with concern expressed about the impact on delayed diagnosis • postponement or cancellation of diagnostic and treatment services Panelists noted that changes in service delivery, such as the use of telehealth, are likely to continue beyond the pandemic and will be useful alongside face-to-face consultations.

DISCUSSION
APAC APCCC 2020 was convened to review how ideal-world consen- • the distinction between "life-extending treatment" and "curative treatment" • the risk of systemic treatment side effects in asymptomatic patients • the significant level of "PSA anxiety" that exists for patients • the complexity of explaining how differences between PSMA PET/CT and conventional imaging findings may influence treatment options Areas of nonconsensus at APCCC meetings often reflect emerging evidence. Examples at APAC APCCC 2020 included: • the lack of a consistent definition of "low disease burden" in the metastatic setting • the need for clarity in the definition of M0CRPC • the impact of newer radiation therapy techniques such as SBRT on outcomes for patients with locally advanced (cT3/4 and/or cN1) or metastatic disease • the evolving field of biomarker testing in identifying treatment targets in metastatic disease APAC APCCC 2020 was conducted against the backdrop of a global pandemic. Panelists described effects on clinical service delivery and clinical trials and highlighted the likely longer term impact on stage at diagnosis and outcomes. Postpandemic implications for service delivery were discussed, including standardization of telehealth and sensechecking the number and frequency of hospital visits for clinical trials.
APAC APCCC 2020 was the second region-wide meeting to discuss management of advanced prostate cancer. The value of shared insights and collaboration across the region were once again apparent, with an ongoing commitment to translating innovations in technologies and treatments into improved outcomes for men with advanced prostate cancer across the region.