key: cord-0907408-wrhjnz8w authors: Greco, Francesco; Altieri, Vincenzo; Esperto, Francesco; Mirone, Vincenzo; Scarpa, Roberto M. title: Impact of COVID-19 pandemic on health-related quality-of-life in uro-oncologic patients: what should we wait for? date: 2020-07-17 journal: Clin Genitourin Cancer DOI: 10.1016/j.clgc.2020.07.008 sha: aa86bcb38ccc261f916b498ffd3912ed0157c35e doc_id: 907408 cord_uid: wrhjnz8w PURPOSE: To investigate the health-related quality-of-life (HRQOL) of uro-oncologic patients whose surgery was postponed without being re-scheduled during COVID-19 pandemic. METHODS: From the 1(st) March to the 26(th) April 2020, major urological surgeries were drastically reduced at our tertiary referral hospital. In order to evaluate the HRQOL outcomes, the SF-36 questionnaire was sent to all patients scheduled for major surgery at our department 3 weeks after the cancellation of the planned surgical procedures due to the COVID-19 emergency. RESULTS: All patients included in the analysis were waiting for surgery since a median time of 52.85 days (IQR 35-72 d). When considering physical characteristics, median PF was 91.5 (IQR 50-100) and median PH was 82.75 (IQR 50- 100) with a median BP of 79.56 (IQR 45-90). Basing on emotional and social aspects, median RE was 36.83 (IQR 0-100) with a median SF of 37.98 (IQR 12.5-90). Mostly of patients reported a loss of energy (median EF 35.28 with an IQR of 15-55) and an increased anxiety (median EWB 47.18 (IQR 20 -75). All patients perceived a reduction of their health conditions with a median GHP of 49.47 (IQR 15-85). Generally, 86% of patients (n=43) referred an almost intact physical function but a significant emotional alteration characterized by a prevalence of anxiety and loss of energy. CONCLUSIONS: Our study suggests that the lockdown which has impacted most operating rooms in Italy could be responsible for an increased anxiety and decrement in health status of the oncological patients. Without any effective real solution, we should expect a new medical catastrophe which will be caused by an increased risk of tumor progression and mortality in uro-oncologic patients. At the end of February 2020, we have experienced the beginning of a new era: a pandemic of new Coronavirus which was found to be sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus (1, 2) and which has completely changed our life. On 31 December 2019, Chinese authorities notified the WHO regarding a novel coronavirus, now designated SARS-CoV-2, that was first reported in Wuhan, China (3, 4) . The virus has now spread worldwide and on 11 March 2020 the WHO defined the disease caused by this virus -COVID-19 -as a pandemic (3, 4) . By the 3 rd April 2020, 1.131.000 confirmed cases and 59.000 deaths had been reported worldwide, with these numbers increasing rapidly every day 2. After China, Italy has been hit the hardest at beginning of the pandemic: 119.827 cases were reported as of 3 rd April 2020, alongside 14.681 deaths due to COVID-19 since the outbreak began. As numbers were rapidly increasing, European governments decided to apply a quarantine and isolation of the citizens in order to reduce the number of infections, thus trying to avoid a collapse of the health system care. Our way to make medicine has been drastically changed and in Italy doctors have been involved in this emergency and in the therapy of COVID-19 patients, disregarding their specialization. Before COVID-19 emergency, one of the most relevant problems of Italian Healthcare system was represented by the significantly long waiting list for oncologic procedures. Since Coronavirus pandemic broke down in our life, all public and private hospitals in North Italy have focused on Covid-19 patients presenting severe breathing symptoms as no therapeutics have yet been proven effective for the treatment of SARS-CoV-2 (5) . But at the same time, it seems that the Italian health care system has forgotten the oncologic patients as any effective solution has been proposed to help these patients. In this study we investigated the health-related quality-of-life (HRQOL) of oncologic patients who were scheduled for surgery in our department and who have been postponed without a new date. Between 1 st January 2020 and 24 th February 2020, we had performed in our department 51 major procedures for prostate cancer, renal cancer and muscle-invasive bladder cancer. Of 51 procedures, 46 were performed by a robot-assisted or laparoscopic approach and 5 procedures by open surgery. From the 1 st March to the 26 th April 2020 as the daily rate of COVID-19 patients admitted to intensive care units has consistently been between 9% and 11% of all patients who are actively infected, our hospital decided to reduce surgical activity and since then only 3 robot-assisted radical prostatectomies (RARPs) for high-risk prostate cancer were performed at our department. Sixtyfive planned major surgical procedures for oncologic diseases were cancelled and postponed in the future. In order to evaluate the HRQOL outcomes, the SF-36 questionnaire (see Appendix, 6,7) was sent by email to all oncologic patients scheduled for major surgery at our department 3 weeks after the cancellation of the operation due to the COVID-19 emergency. The SF-36 consisted of 36 multiple-choice questions measuring eight distinct domains: physical functioning (PF), role limitations due to physical health (PH), role limitations due to emotional problems (RE), energy/fatigue (EF), emotional well-being (EWB), social functioning (SF), bodily pain (BP), general health perceptions (GHP). Scores for each scale ranged from 0-100, with higher scores indicating higher function or well-being (8, 9) . The patients were divided according to the disease in 4 groups: prostate cancer (PCa) (planned for radical prostatectomy), muscle-invasive bladder cancer (MIBCa) (planned for radical cystectomy), upper urinary tract urothelial cancer (UTUC) (planned for radical nephroureterectomy) and renal cell carcinoma (RCC) (planned for partial/radical nephrectomy). Patients with prostate cancer were stratified according to the D'Amico risk criteria (10) on clinical features: low risk (PSA ≤10 ng/ml, ≤ cT2a, and biopsy Gleason ≤ 6), intermediate risk (PSA >10 and ≤ 20 ng/ml, cT2b, or biopsy Gleason 7), and high risk (PSA >20 ng/ml, lower than cT2b, or biopsy Gleason ≥8). External beam radiation therapy was proposed as alternative therapy for Patients with advanced tumor stage (prostate cancer high risk according to D'Amico criteria or locally advanced or with nodal clinical disease, renal cancer with IVC thrombus and MIBCa > pT3) were excluded from the analysis. Moreover, we also excluded patients presenting psychic or distress disorders such as anxiety and depression or Charlson Comorbidity index (CCI) > 2 (11) at diagnosis and before COVID-19 emergency. Fifty patients were included in the analysis whereas 15 patients did not meet the inclusion criteria. MIBCa, 4 patients reported a non-metastatic UTUC and 7 patients presented a cT1b RCC with a median tumor size of 4.5 cm (IQR 2.8-6). Median age was 65.5 years old and median CCI was 1.39 (IQR 0-2). Thirty-eight patients were males and 12 patients were females. All patients included in the analysis were waiting for surgery since a median time of 52.85 days (IQR 35-72 d). All patients were married and lived with their family. Thirty-five patients were fulltime employed and 15 patients were retired. Generally, 86% of patients (n=43) referred an almost intact physical function but a significant emotional alteration characterized by a prevalence of anxiety and loss of energy ( Fig. 1 and 2) As Covid-19 spread around the globe, governments have imposed quarantines and isolation on an unprecedented scale. China locked down whole cities and also in Italy our politicians have imposed draconian restrictions throughout the country. In the United States, thousands of people have been subjected to legally enforceable quarantines or are in "self-quarantine." The federal government has also banned entry by non-U.S. nationals traveling from China, Iran, and most of Europe and is screening passengers returning from heavily affected countries. Still, the numbers of cases and deaths continue to rise (12) . Unfortunately, since the COVID-19 outbreak in our region, Italian government focused its attention exclusively to COVID-19 patients, "forgetting" those patients who were not infected by the virus but who needed access to health care system as affected by cancer. considering that a real multimodal approach can be probably applied for patients choosing RP, whereas patients choosing RT first rarely receive salvage RP (15). In this study, we focused for the first time in literature on the impact of postponement of surgeries due to COVID-19 emergency on the on health-related quality-of-life of uro-oncologic patients by using the SF-36 questionnaire. When evaluating the results of the questionnaire, we could find that mostly of patients (86%) reported an almost normal physical activity but a loss of energy and an increased anxiety and depression. In order to avoid bias, we excluded from the analysis all patients with severe comorbidities (CCI > 2) and/or patients who showed psychologic or distress disorders before COVID-19 emergency. Furthermore, we also excluded patients with advanced or metastatic tumors where the disease could represent the 1 st reason for anxiety and depression. Generally, all patients perceived a reduction of their health conditions with a median GHP of 50.45 (IQR 15-85). Recent research findings in individuals with distress disorders such as major depression and anxiety disorders suggest an important role of inflammation in the pathophysiology of these conditions (17, 18) and inflammatory biomarkers are elevated in many patients with major depressive disorder and anxiety disorders (19) . Moreover, fatigue impact, pain effects, depression symptoms and anxiety symptoms are associated with work and general activity impairment (20) . Clinically relevant anxiety occurs in 7% to 30% of oncology patients and 20% to 40% of their family caregivers (21, 22) and it is oft characterized by dyspnea, fatigue, nausea and pain and poorer quality of life (QOL) (23, 24) . Furthermore, most of these reported studies also highlighted a significant association between higher levels of anxiety and depression and decrements in health status. Based on the evidence that supports a role for inflammatory mediators in stress and anxiety (25) This study could demonstrate that variations in three cytokine genes (i.e., interleukin (IL) 1 beta, IL1 receptor 2 (IL1R2), nuclear factor kappa beta 2 (NFKB2)) were associated with trait anxiety, and variations in two genes (i.e., IL1R2, tumor necrosis factor alpha (TNFA)) were associated with state anxiety, thus contributing to higher levels of anxiety in oncology patients and their family caregivers. Actually, basing on the data concerning the incidence of urologic tumors, it could be hypothesized a further extension in Italy of the waiting list for cancer diseases, which could be subsequently associated to increased risk of psychologic disorders and decrements in health status in the oncological patients. In 2018 Ferlay et al. evaluated cancer incidence and mortality estimates for 25 major cancers in Europe: PCa reported an incidence of 449.800 cases/100.000 inhabitants, bladder cancer presented an incidence of 197.100/100.000 whereas an incidence of 136.500/100.000 was reported for renal cancer (27) . If the hospitals should continue to reduce elective surgical activity due the COVID-19 pandemic, then it could be taken several months to treat all oncologic patients waiting for surgery. Indeed, we should also consider that most of the oncologic patients will require a clinical re-staging of the disease, thus increasing waiting time for surgery and the healthcare spending. Limitations of the study are represented by the small cohort of the included patients and by the lack of a control group. Nevertheless, we believe that the sample is sufficiently reliable to truly reveal the physical and emotional conditions of our patients waiting for an oncologic surgery during COVID-19 emergency. Our study suggests that the lockdown due to COVID-19 pandemic, which has impacted most operating rooms in Italy, has been responsible for an increased anxiety and decrements in health status of the oncological patients. Considering the actual data on cancer incidence, a great effort should be made by the institutions for organizing new COVID-free hospitals, which could face the new emergency represented by the lengthened surgical waiting list for uro-oncologic diseases. Without any effective real solution, we should expect a new medical catastrophe which won't be caused by Coronavirus but by an increased risk of tumor progression and mortality in those patients who actually present a confined tumor disease and who could be probably saved by an immediate surgical therapy. All authors disclose any actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within that could inappropriately influence (bias) the work. The Epidemiology and Pathogenesis of Coronavirus Disease (COVID-19) Outbreak Genomic Characterisation and Epidemiology of 2019 Novel Coronavirus: Implications for Virus Origins and Receptor Binding Urology in the time of corona World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19) A Trial of Lopinavir-Ritonavir in Adults Hospitalized With Severe Covid-19 Robotic Intracorporeal Orthotopic Neobladder: Urodynamic Outcomes, Urinary Function, and Health-related Quality of Life Factors Predicting Health-Related Quality of Life Recovery in Patients Undergoing Surgical Treatment for Renal Tumors: Prospective Evaluation Using the RAND SF-36 Health Survey The RAND 36-Item Health Survey 1.0 Biochemical outcome after radical prostatectomy, external beam radiation ther-apy, or interstitial radiation therapy for clinically localized prostate cancer Age-adjusted Charlson Comorbidity Index as a prognostic factor for radical prostatectomy outcomes of very high-risk prostate cancer patients Covid-19 -The Law and Limits of Quarantine Considerations in the triage of urologic surgeries during the COVID-19 pandemic Assessing the Burden of Nondeferrable Major Urooncologic Surgery to Guide Prioritisation Strategies During the COVID-19 Pandemic: Insights from Three Italian High-volume Referral Centres The efficacy and safety of radical prostatectomy and radiotherapy in high-risk prostate cancer: a systematic review and meta-analysis Pathways for Urology Patients During the COVID Anti-inflammatory treatments for mood disorders: Systematic review and meta-analysis Evidence for inflammationassociated depression Imaging the role of inflammation in mood and anxiety-related disorders The association of fatigue, pain, depression and anxiety with work and activity impairment in immune mediated inflammatory diseases Psychosocial morbidity in prostate cancer: II. A comparison of patients and partners Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender, and age The frequency and correlates of dyspnea in patients with advanced cancer Assessing the independent contribution to quality of life from anxiety and depression in patients with advanced cancer Anxiety disorders and inflammation in a large adult cohort Cytokine gene variations associated with trait and state anxiety in oncology patients and their family caregivers. Support Care Cancer Cancer Incidence and Mortality Patterns in Europe: Estimates for 40 Countries and 25 Major Cancers in 2018