key: cord-0814351-b5e8wa0k authors: Poon, Darren Ming‐Chun; Chan, Chi‐Kwok; Chan, Tim‐Wai; Cheung, Foon‐Yiu; Ho, Lap‐Yin; Kwong, Philip Wai‐Kay; Lee, Eric Ka‐Chai; Leung, Angus Kwong‐Chuen; Leung, Simon Yiu‐Lam; So, Hing‐Shing; Tam, Po Chor; Ma, Wai‐Kit title: Prostate cancer management in the era of COVID‐19: Recommendations from the Hong Kong Urological Association and Hong Kong Society of Uro‐oncology date: 2021-04-15 journal: Asia Pac J Clin Oncol DOI: 10.1111/ajco.13579 sha: 65a612e8483db6ca8a8e746532f873ae9a5f7291 doc_id: 814351 cord_uid: b5e8wa0k 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. Since late 2019/early 2020, coronavirus disease 2019 (COVID-19) has quickly emerged from a single-city cluster of cases into a global pandemic, with over 4.5 million cases and 300 000 deaths reported as of May 15, 2020 . 1 Largescale antiepidemic measures have been implemented in almost every country, and yet many are struggling to reduce transmission rates that have remained at high levels. It is generally believed that the pandemic will continue for months to years. At this phase, proactive response and coordination are urgently needed not only in terms of case detection, infection control, and antiviral treatment, but also in the interdisciplinary care of patients across medical specialties. Cancer patients need extra care during this period because many are at an elevated risk of infection, 2,3 presumably from an immunosuppressive state due to poor performance, treatment-related adverse events, and older age compared with healthy individuals. In this regard, both the disease stage and treatment modalities should be considered. Prostate cancer (PC) patients can be in very different disease stages, from very low-risk localized conditions to high-burden metastatic diseases. Treatments may range from active monitoring to radical prostatectomy (RP) and combination systemic treatments. With regard to COVID-19, the UK National Institute for Health and Care Excellence (NICE) has published Rapid Guidelines on systemic anticancer therapy and radiotherapy (RT). 4, 5 For robotic surgery and endoscopy during the pandemic, clinicians may refer to the European Association of Urology Robotic Urology Section and Asian Pacific Society for Digestive Endoscopy guidelines. 6, 7 The latest medical literature has also elaborated on various aspects of urological (including cancer) management in COVID-19, including the following: treatment pathways, 8 surgery triage guidance, 9 radiation recommendations, 10 and a comprehensive literature review. 3 The present article provides a detailed set of recommendations specific to PC management during the COVID-19 pandemic. On April 16, 2020, two professional associations-the Hong Kong Urological Association (HKUA) and Hong Kong Society of Uro-onology (HKSUO)-met via an online conference platform, with the objective of producing a set of recommendations to minimize the risk of infection, while avoiding unnecessary treatment delays or compromised outcomes. Hong Kong is a city with among the largest urban population and numbers of inbound tourists and air transit passengers in the world. Although the first cases of COVID-19 were reported in January, the rates of transmission and mortality have stayed relatively low, with currently (April 2020) slightly over 1000 cases and four deaths reported. Based on an evidence-based approach, these discussions aimed to combine the specialist expertise of both associations and draw from Hong Kong's experiences in the COVID-19 as well as the 2003 Severe Acute Respiratory Syndrome (SARS) epidemics. It is hoped that these recommendations will be helpful to clinicians both in Asia and globally. To obtain the latest relevant literature on the relationship between PC management and the coronavirus outbreak, a literature search was conducted in multiple medical-related databases, including PubMed, Ovid, ClinicalKey, Proquest, and Google Scholar, using combinations of the following keywords: "COVID-19," "coronavirus," "epidemic," "pandemic," "prostate cancer," "urology," "prostatectomy," "endoscopy," "radiotherapy," "chemotherapy," and "systemic." A total of 53 articles (42 of which were published in 2020) were selected for further discussions. The panel provided detailed recommendations for the management of PC patients at different stages, regarding the risks associated with specific procedures. Figure 1 presents a schematic illustration of the framework and highlights some key recommendations. During the COVID-19 pandemic, many places are currently experiencing shortages of medical and laboratory resources and supplies. Priority for diagnostic procedures should be given to patients who may be more urgently in need of starting treatment, which would also help to reduce infection risks. 8 For PC, these are generally patients with suspected metastatic, locally advanced, or high-risk disease The panel also came to a general agreement to reserve the use of invasive diagnostic procedures for patients with highly suspicious conditions, 13 Most guidelines stratify localized PCs into low-, intermediate-, and high-risk categories. 16 In low-risk patients (those with PSA < 10 ng/mL, Gleason score ≤ 6, staged T1/T2), treatment may be temporarily deferred during the epidemic, when accompanied by regular monitoring 17 Physicians should discuss with the patient any special medical arrangements made during the pandemic such as whether the patient would be willing to defer treatment. [11] R1.3 Because COVID-19 can be asymptomatic, infection control protocols should be closely followed during any diagnostic or therapeutic procedure, and the patient should be assessed for travel history and symptomatology beforehand. [12] 2. Diagnostic procedures R2.1 Priority should be given to patients with suspected high-risk, locally advanced, or metastatic diseases. [8] R2.2 Invasive diagnostic procedures should be reserved for patients with highly suspicious conditions, that is, a PSA level of ≥ 20 ng/mL, high PSA density, and/or abnormal DRE results. [13] R2.3 For patients with PSA levels < 20 ng/mL, combined radiological (eg, MRI) and serological (eg, PHI) assessment is preferred. In case of uncertainty, further assessments, such as urinary RNA analysis, may also be undertaken before biopsy is considered. [14] 3. Localized PC R3.1 For low-risk localized PC (PSA < 10 ng/mL, Gleason score ≤ 6, staged T1/T2), treatment may be temporarily deferred and accompanied by regular monitoring such as PSA testing every 3 months and MRI scanning every year. As usual, active surveillance is important and highly recommended. [17, 18] R3.2 In high-risk patients, treatment should not be delayed. When combining RT with ADT, the latter may be prolonged for up to 1 year before the commencement of RT. Surgeries should proceed while resources allow (eg, staffing and personal protective equipment). [13, [19] [20] [21] R3.3 Intermediate-risk patients may be subdivided into those with favorable and unfavorable intermediate risks, as in the NCCN guideline, and managed as low-and high-risk patients, accordingly. [18] 4. Metastatic PC To reduce the infection risks associated with operative procedures, medical castration is preferred over surgical castration (orchiectomy). The pros and cons of LHRH agonists and antagonists should be discussed with the patient. Longer-acting agents may help to reduce the number of required hospital visits. [22] R4.2 Immunosuppression from chemotherapy may increase the risks of fever and infection. While chemotherapy can produce significant survival benefits in mHSPC patients, nonchemotherapeutic alternatives (eg, abiraterone and enzalutamide) should be considered. When administering chemotherapy, prophylactic G-CSF should be given to reduce the risk of febrile neutropenia. [4, 23, 25, 26] R4.3 Ultrahypofractionated prostate RT (6 Gy in 6 weekly fractions) as in the STAMPEDE M1|RT protocol may be adopted for low-burden metastatic disease (see also R6.1). [27] 5. Prostatectomy Patients may be screened for COVID-19 before undergoing prostatectomy that involves prolonged ventilation or robotic-assisted laparoscopy, to minimize any added risk of respiratory and aerosol transmission. The panel recommended medical over surgical castration during the epidemic, because they are associated with similar survival rates, 22 Prophylactic granulocyte colony-stimulating factors can reduce the risk of developing chemotherapy-induced febrile neutropenia, 25 including in Chinese patients, 26 and should be prescribed during this period. For low-volume metastatic PC, the latest STAMPEDE M1|RT results showed that prostate RT significantly prolonged overall survival. 27 During the COVID-19 epidemic, in these cases, ultrahypofractionation (6 Gy in 6 weekly fractions) may be used, and lifelong ADT may be started up to 3 months before RT, according to the STAMPEDE protocol (R4.3; see also section 3.6). While it is good clinical practice to apply a high level of infection control to surgery, the panelists noted two aspects of prostatectomy that may increase the risk of SARS-coronavirus-2 (SARS-CoV-2) infection within the operating theater or patient ward: prolonged ventilation and robotic-assisted laparoscopy. Prolonged ventilation may be required in patients suffering from certain respiratory conditions such as sleep apnea. There might be an increased risk of infection through contamination in the ventilation system or during intubation. 28 Second, robotic-assisted laparoscopy makes use of an artificial pneumoperitoneum, which is aerosol generating. 6, 7, 28 Because SARS-CoV-2 is likely capable of airborne transmission, 29 caution should be exercised. When a prostatectomy involves any of these two aspects, the patient should be screened for COVID-19 beforehand (R5.1). The use of immobilization devices (eg, endorectal balloons) and image-guiding implants (eg, gold seed fiducial markers) may require invasive procedures and extended hospital stays. 10 The potential increased risk of SARS-CoV-2 infection should be considered (R6.3). While there may be an infection risk associated with hospital visits, and patients may not find it convenient or safe to leave home in this period, some supplementary care services may be provided to improve accessibility to healthcare. 31 A simple way is to provide some services over the phone including follow-up calls, explanations of testing results, and treatment reminders (R7.1). The epidemic can affect PC management in various ways and strain overall healthcare resources. Interdisciplinary expertise remains vital for developing comprehensive response strategies, accurate risk assessments, and effective workflow coordination (R8.1). To minimize the risk of infection, regular interdisciplinary meetings may be conducted through secured online platforms. 32 It is worth noting that an evidence-based approach to medicine may become obscure during an epidemic. On the one hand, little is known about the severity and mortality of COVID-19 among cancer patients, 33 There may be a concern that the selection of certain management modules over others will transfer the risk of infection from one team of healthcare professionals to another. For example, the choice of combined MRI scan and PHI test over biopsy may transfer the risk from the urology to the radiology team. Our panel agreed that biopsy is more invasive than MRI scan and PHI test, requires closer physical contact, and involves a longer hospital stay. However, it is possible that the radiology laboratory may be at an elevated risk of contamination from suspected COVID-19 patients undergoing chest imaging. Thus, some further risk assessments and discussions may still be needed, which highlights the importance of interdisciplinary collaboration during the epidemic. These recommendations have some limitations. First, they apply to an urban setting where tertiary medical care is routinely available. It was assumed that resources have become constrained during the epidemic, but not severely deficient. If a worst-case scenario were to happen, these recommendations will provide a basis for action, but further adaptations will be needed. For example, if operating theaters become excessively contaminated, surgeries might need to be further deferred. Conversely, our panelists noted that infection control may be less difficult in privately operated hospitals than public ones due to a lower patient-to-staff ratio. Thus, some medical procedures may be somewhat less risky to perform in the private setting. Second, as our understanding of COVID-19 deepens, these recommendations can be further refined. For example, numerous reports have documented viral transmission through asymptomatic individuals, 35 as well as renewed viral positivity in the throat swabs of discharged patients. 36 When we understand these phenomena more clearly, our practices may need to change accordingly. Another possibility to consider is the development of a SARS-CoV-2 vaccine. If a vaccine becomes available, the suitability of vaccination in PC patients will also need to be determined. These practical recommendations cover various management modules for patients at different stages of PC during the COVID-19 pandemic. Clinicians working with PC patients may follow these recommendations, to minimize the risk of infection while avoiding unnecessary delays and compromises in management outcomes. This study did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. 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