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Effect of COVID-19 pandemic on diagnosis and treatment pattern of prostate cancer: a comprehensive literature review, phase 1

Soo Young Hwang1, Simona Ippoliti2, Petre Cristian Ilie3, Pinar Soysal4, Ai Koyanagi5,6, Hyunho Han7, Jae Il Shin8,*https://orcid.org/0000-0003-2326-1820, Lee Smith9
Author Information & Copyright
1Yonsei University College of Medicine, Seoul, Republic of Korea
2Urology Department, Hull University Teaching Hospitals, Hull, UK
3Urological Department, Norfolk and Norwich University Hospital, Norwich, UK
4Department of Geriatric Medicine, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey
5Research and Development Unit, Parc Sanitari Sant Joan de Déu, CIBERSAM, ISCIII, Universitat de Barcelona, Fundacio Sant Joan de Deu, Sant Boi de Llobregat, Barcelona, Spain
6ICREA, Pg. Lluis Companys 23, Barcelona, Spain
7Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea
8Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
9Centre for Health Performance and Wellbeing, Anglia Ruskin University, Cambridge, UK
*Correspondence: Jae Il Shin, E-mail: shinji@yuhs.ac

© Copyright 2022 Life Cycle. This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: Oct 28, 2022; Revised: Nov 22, 2022; Accepted: Dec 01, 2022

Published Online: Dec 04, 2022

Abstract

Since its outbreak in late 2019, the COVID-19 pandemic has brought many changes to medical practice, including the care and management methods regarding prostate cancer. Patients with prostate cancer are exposed to high risk of infection, hospitalization, and death due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while other elements including male gender, old age, and pre-existing comorbidities increased the possibility of infection. Although patients with prostate cancer need intensive support and care, high concerns of infection resulted in delay or avoidance of medical care, especially during the initial phase of the pandemic, which led to needs of revisions in diagnostic procedures and treatment plans. Our review illustrates the changes that have occurred in prostate cancer diagnosis, treatment, and prognosis since the emergence of the COVID-19 pandemic. We further conducted a review on topics recently being highlighted which include the protective role of androgen deprivation therapy on SARS-CoV-2 infection, vaccination and immune response in patients with prostate cancer, and the outcomes of altered treatment plans. As with the many efforts in treating cancer since the outbreak of COVID-19, identifying the changes in research and clinical practice of patients with prostate cancer worldwide is essential in providing appropriate patient care in rapidly changing circumstances.

Keywords: COVID-19; SARS-CoV-2; prostate cancer; urology

1. Introduction

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) near the end of 2019 caused a global pandemic that led to unprecedented measures of lockdowns and restrictions in order to slow the rapid development of the virus.[1] The COVID-19 pandemic has also brought many changes to medical practice, including urology practice, and more specifically, the care and management regarding prostate cancer.

Patients with cancer, compared with the general public, are at a greater risk of infection due to the immunosuppressed status of some patients, which potentially exposes them to more severe infections as well as serious complications.[2] Other negative prognostic factors which include male gender, old age, and pre-existing comorbidities, pose additional risks to those patients with prostate cancer.[2] Patient concerns about COVID-19 have resulted in delay or avoidance of medical care, even cases needing urgent or emergency care.[2] Telemedicine and mobile health are seen as successful tools that help diagnosing and monitoring patients while reducing transmission of COVID-19, and vaccination status became a factor that influenced patient management and treatment.[3]

The aim of this paper is to analyze the evolving trend in the urological clinical practice, particularly in the diagnosis, treatment, and prognosis of prostate cancer after the occurrence of the COVID-19 pandemic. We further reviewed novel topics related to the association between COVID-19 and prostate cancer which are recently receiving, as well as the management and nature of the disease itself (Table 1 and 2).

Table 1. Main findings of studies on COVID-19 and prostate cancer
Main findings
1. Androgen deprivation therapy (ADT) and COVID-19
- There is no significant relationship between the protective role of ADT on COVID-19 infection and mortality.[6-13]
2. Diagnosis, treatment, and mortality of patients with prostate cancer during the COVID-19 pandemic
- Local anesthetic transperineal prostate biopsy (LATP) was the preferred method of prostate biopsy by clinicians during the pandemic.[16]
- Decrease in diagnostics and treatment was pronounced during the first lockdown with a rebound late-pandemic.[19-26]
- Patients were more likely to have a malignant pathology at diagnosis[22] or in a more advanced stage after prostatectomy.[27]
- Clinical visits, prostate biopsy, and men enrolled in active surveillance were significantly lower while the number of advanced and metastatic prostate cancer cases increased during a year of the pandemic.[27]
- Although there was a consistent reduction in radical prostatectomy (RP), radiotherapy (RT) had a lesser reduction or was increased in some studies.[20, 21, 23, 27]
- Overall hospitalization and mortality rates were higher in patients with prostate cancer and COVID-19 compared with patients with solid cancers and COVID-19.[28]
3. The effect of delayed treatment
- Patients with localized prostate cancer who were treated during the pandemic had a higher risk of extra-prostatic disease and lymph node invasion due to a delay in the administration of curative-intent therapies.[31]
- There is no significant difference in early adverse oncologic outcomes between intermediate, high-risk patients who received immediate RP and any level of delay up to 12 months.[32]
- Overall and cancer-specific survival was significantly worsened among intermediate-risk patients receiving monitoring compared to immediate RP (but not in low-, high-risk patients).[33]
4. Quality of life of patients with prostate cancer during the COVID-19 pandemic
- Patients with prostate cancer and delayed operations had higher state anxiety than trait anxiety, especially higher in young patients[34]
- Cognitive deterioration was more frequent in patients treated with ADT, even more after the COVID-19 pandemic.[35]
5. Vaccination and prostate cancer
- CD4+ T cells of SARS-CoV-2-unexposed patients with hormone-resistant metastatic prostate cancer had decreased CD4+ T cell immune responses to antigens from SARS-CoV-2 spike glycoprotein but not from the spiked glycoprotein of the human coronavirus 229E (HCoV-229E). [36]
- Similar median titers of neutralizing antibodies against SARS-CoV-2 were observed in twenty-five prostate cancer under treatment with androgen receptor-targeted agents such as abiraterone or enzalutamide with healthy controls.[37]

Abbreviations; ADT, androgen deprivation therapy; LATP, local anesthetic transperineal prostate biopsy; RP, radical prostatectomy; RT, radiotherapy

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Table 2. Characteristics of included studies
Author, year Study period Study design Exposure Outcome Database/cohort
Duarte, 2021[13] Outbreak of COVID-19 to April, 2021 Retrospective cohort ADT versus non-ADT Cumulative incidence of Death Brazilian Unified Health System
Fujiwara, 2021[38] Apr to Jun, 2020 Retrospective cohort (pilot study) Prostate cancer which switched from GnRH antagonist to long-acting LH-RH agonist Serum testosterone, PSA Cancer Institute Hospital, Japanese Foundation for Cancer Research
Gedeborg, 2021[39] Mar to Dec, 2020 Case-control ADT COVID-19 mortality Prostate Cancer data Base Sweden (PCBaSe) RAPID 2019
Gedeborg, 2021[7] 2015 to 2020 Retrospective cohort ADT COVID-19 mortality Prostate Cancer data Base Sweden
Klein, 2021[8] Mar to Jun, 2020 Prospective cohort ADT COVID-19 positivity and disease severity Cleveland, Ohio
Jiménez-Alcaide, 2021[9] Mar to May, 2020 Retrospective cohort ADT COVID-19 severity Hospital Universitario Fundación Alcorcón
Koskinen, 2020[10] Mar to May, 2020 Retrospective cohort ADT COVID-19 positivity Hospital District of Helsinki and Uusimaa, Finland
Schmidt, 2021[11] Mar, 2020 to Feb, 2021 Retrospective cohort ADT COVID-19 mortality COVID-19 and Cancer Consortium registry
Kwon, 2021[12] Feb to Dec, 2020 Retrospective cohort ADT COVID-19 incidence University of California Health System registry
Montopoli, 2020[5] Start of COVID-19 to Apr, 2020 Retrospective cohort ADT COVID-19 incidence 68 hospitals in Veneto, Italy
Karimi, 2021[40] Search: Dec, 2020 Meta-analysis ADT COVID-19 infection risk, hospitalization rate, ICU admission, and mortality risk Four eligible studies
Motlagh, 2022[15] Search: July, 2021 Meta-analysis ADT COVID-19 infection risk, severity 6 Retrospective studies
Stroman, 2021[16] Apr to May, 2020 Cross-sectional Prostate biopsy method Centres in United Kingdom
Caffo, 2020[41] Feb to Jun, 2020 Retrospective cohort Metastatic castrate-resistant prostate cancer COVID-19 incidence 20 Italian oncological centres
Chakravarty, 2021[28] Mar to Dec, 2020 Retrospective cohort Prostate cancer COVID-19 hospitalization and mortality Mount Sinai Hospital system
Deukeren, 2022[22] Mar to May, 2020 Cross-sectional Prostate cancer diagnosis Netherlands Cancer Registry (NCR)
Fallara, 2021[23] Mar to Jun, 2020 Cross-sectional Prostate cancer diagnosis and staging, treatment National Prostate Cancer Register (NPCR) of Sweden
Ferrari, 2021[19] 2016 to 2020 Cross-sectional Prostate cancer routine screening University Hospitals of Verona
Klaassen, 2022[29] Jan, 2018 to Mar, 2021 Retrospective cohort Race Prostate biopsies and diagnoses Veterans Affairs Health Care System
Bernstein, 2021[30] Mar to May, 2020 Retrospective Cohort Race Prostatectomy rate Pennsylvania Urologic Regional Collaborative (PURC)
Nossiter, 2022[21] Mar to Dec, 2020 Cross-sectional Prostate cancer diagnosis and treatment English National Health Service
Pepe, 2021[27] 2020 to 2021 Cross-sectional Prostate cancer diagnosis and treatment Catania, Italy
Sciarra, 2020[20] Mar 2020 Descriptive study Diagnostic, therapeutic elective procedures requested and performed for cancer management Rome, Italy
Surasi, 2021[18] 2021 Descriptive study Prostate MRI studies, biopsies Radiologists from five continents
Ip, 2021[25] Jun 2018 to Jun 2021 Temporal trend analysis Cancer diagnostics, treatments, and physician attendances Services Australia Medicare Benefits Schedule Item Reports
Kaufman, 2021[24] Jan 2018 to Dec 2020 Temporal trend analysis PSA, prostate biopsy, and diagnoses Quest Diagnostics database
Barrett, 2021[42] Jan 2019 - Oct 2020 Analysis of descriptive statistics and interrupted time series Prescription of gonadorelins English Prescribing Dataset
Ginsburg, 2020[32] 2010 to 2016 Retrospective cohort Delayed radical prostatectomy Oncological outcome National Cancer Database
Lee, 2022[43] 1988 to 2018 Retrospective cohort Delayed radical prostatectomy Time of castration-resistant prostate cancer, metastasis, and all-cause mortality SEARCH cohort, U.S.
Diamand, 2021[44] Mar 2012 to Sep 2019 Retrospective cohort Delayed radical prostatectomy Oncological outcome European centers (Belgium, France, Switzerland, and Italy)
Zattoni, 2021[31] Mar to Dec, 2020 Retrospective Cohort Delay in radical Prostatectomy Risk of adverse pathologic findings at RP 8 European tertiary referral centers
Chan, 2021[33] Search: May, 2020 Meta-analysis Delayed treatment Disease prognosis 4 randomized trials and 33 observational studies
Loeb, et al. 2021[45] Dec 2019 to April 2020 Computational linguistic ethnography analysis Prostate cancer Linguistic tone and topic of discussion online Inspire Us TOO Prostate Cancer online support and discussion, Reddit
Irusen, 2021[46] Jul to Sep, 2020 Prospective longitudinal study COVID-19 Corona virus anxiety scale, state-trait anxiety inventory, the connor-davidson resilience scale, and multidimensional scale of perceived social support Cape Town, South Africa
Araújo, 2022[35] Before vs after COVID-19 pandemic Prospective Cohort ADT Montreal cognitive assessment NEON-PC, Portuguese Institute of Oncology of Porto
Kizilkan, 2021[34] Mar to Jun, 2020 State-trait anxiety inventory I and II and beck depression inventory Ankara City Hospital, Turkey
Lopez, 2020[47] Search: Nov, 2019 Meta-analysis Fatigue, quality of life, lean body mass, and fat mass 3 randomized trials
Liontos, 2021[37] 2021 Prospective cohort Prostate cancer under treatment with ARTA who were vaccinated for COVID-19 Neutralizing antibody against COVID-19 Athens, Greece
Notohamiprodjo, 2022[48] Jun to July, 2021 Retrospective cohort COVID-19 vaccination Prevalence, temporal response, and characteristics of vaccine-associated lymphadenopathy Munich, Germany

Abbreviations; ADT, androgen deprivation therapy; GnRH, gonadotropin-releasing hormone; LH-RH, luteinizing hormone releasing hormone; PSA, prostate-specific antigen.

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2. Androgen deprivation therapy and COVID-19

Cell surface transmembrane serine protease 2 (TMPRSS2) and the angiotensin-converting enzyme 2 (ACE2) protein are two critical molecular and clinical targets reported to facilitate the entry of SARS-CoV-2 into host cells.[4] TMPRSS2 is also an androgen-responsive gene responsible for prostate tumorigenesis, and the hypothesis that the androgen-dependent expression of TMPRSS2 in the lung may increase men’s susceptibility to severe COVID-19 symptoms led to several clinical studies to examine this relationship.[4]

A study of 9,280 patients with SARS-CoV-2 infection in Veneto was the first clinical study to propose that patients with prostate cancer receiving androgen deprivation therapy (ADT) had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive the ADT and had an even lower risk compared to those with any other type of cancer.[5] This study caused much debate over the relationship and protective role of ADT on COVID-19 infection or mortality, but several following clinical studies demonstrated no clear evidence in support of such effect.[6-13]

A study exclusively on patients with metastatic castrate-resistant prostate cancer during the initial phase of the pandemic confirmed the rate of infection as 2.3% and mortality rate of 38.2%. Such results show a higher death rate compared to other studies with a high proportion of patients in remission or treated with curative intent.[14] Also, a meta-analysis of four studies concluded that the overall incidences of COVID-19 among patients with prostate cancer receiving ADT was 2.7% and the mortality rate was 22.7% (Table 3). Moreover, ADT did not decrease the risk of any of the major outcomes such as infection risk, hospitalization rate, intensive care unit (ICU) admission, and mortality risk.[15] The summarized risk ratio of SARS-CoV-2 infection risk in patients with prostate cancer under ADT versus no ADT or the severity of COVID-19 in patients under ADT versus no ADT was 0.80 (95% CI 0.44 to 1.47) and 1.23 (95% CI 0.90 to 1.68), respectively, in a separate meta-analysis.[15]

Table 3. Summary of four meta-analyses on COVID-19 and prostate cancer
Author, year N. of study estimates Main outcome Effect metrics Results
Karimi, 2021[40] 4 ADT (+) versus ADT (-) Odds ratio (95% CI) COVID-19 Infection Risk, 0.63 (0.27-1.48, p=0.29); hospitalization rate, 0.51 (0.10-2.53, p=0.41); ICU admission, 1.11 (0.43-2.90, p=0.82); and mortality risk, 1.21 (0.34-4.32, p=0.77)
Motlagh, 2022[15] 4 COVID-19 infection risk in patients with prostate cancer under ADT vs. no ADT Relative risk (95% CI) 0.80 (0.44-1.47)
5 Severity of COVID-19 in patients with prostate cancer under ADT versus no ADT 1.23 (0.90-1.68)
Chan, 2021[33] 4 (RCTs) A. Expectant management versus immediate RP
B. Cancer-specific survival in expectant management versus immediate RP
Hazard ratio (95% CI) A. 1.21 (1.08-1.37, p<0.01)
B. 1.63 (1.26-2.10, p<0.001)
10 (observational studies) Positive surgical margin in 3 months of NHT and delayed RP versus immediate RP 0.45 (0.37-0.54, p<0.01)
Lopez, 2020[47] 3 Supervised versus non-supervised exercise period (during COVID-19) Standard mean difference (95% CI) Fatigue, 0.2 (-0.6 to 0.2, p=0.090); quality of life, 0.0 (-1.4 to 1.5, p=0.810)
Mean difference (kg; (95% CI) Fat mass 0.5 (-0.4 to 1.5, p=0.141); lean mass 0.0 (-1.2 to 1.2, p=0.810)

Abbreviations; ADT, androgen deprivation therapy; GnRH, gonadotropin-releasing hormone; LH-RH, luteinizing hormone releasing hormone; NHT, neoadjuvant hormonal therapy; PSA, prostate-specific antigen; RCT, randomized controlled trial; RP, radical prostatectomy.

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3. Diagnostics, treatment, and mortality

A cross-sectional study on the diagnostics of prostate cancer in 148 centers in the UK shows interesting findings that the local anesthetic transperineal prostate (LATP) biopsy was the preferred method of prostate biopsy by clinicians during the pandemic; the reduction of general anesthetic transperineal prostate (GATP; 64%) and local anesthetic transrectal ultrasound-guided transrectal ultrasound (60%) was greater than the reduction of LATP (20%).[16] The transit from transrectal biopsy to transperineal biopsy started in the UK in 2019 mainly due to the decreased risk of post-procedural sepsis[17], and the pandemic has accelerated this shift. There was an overall decrease in the diagnostics during the pandemic, and according to a survey of radiologists from five continents, the number of prostate MRIs decreased significantly with a median (range) of 20 (0 to 135) per week before the COVID-19 pandemic versus 10 (0 to 30) during the lockdown period and 15 (0 to 125) after lockdown.[18]

A dramatic decline in routine prostate cancer screening was observed during the first peak of COVID-19 outbreak in the Verona province of Italy.[19] This was compensated in the post-lockdown period, with the annual number not differing significantly in 2020 compared to the previous four years.[19] In March 2020, there was a great surge in COVID-19 cases in Italy and all management experienced a significant reduction with the exception of medical therapies for advanced hormone-sensitive or castration-resistant prostate cancer.[20] During the first lockdown in England, there was a 30.8% reduction (22,419 during first lockdown versus 32,409 in 2019) in the number of men with newly diagnosed prostate cancer compared to 2019, with men being at a more advanced stage and slightly older (stage IV, 21.2% versus 17.4%, stage IV in elderly [≥70 years], 57.9% versus 55.9%).[21] Also, there was a reduction in radical prostatectomies by 26.9% and external beam radiotherapy by 14.1%.[21] During the first wave of COVID-19 in the Netherlands, an initial decline of 17% of prostate cancer diagnoses was observed while the number restored to approximately 95% from May while stage at diagnosis and radical prostatectomy volumes were comparable to 2018 to 2019.[22] In Sweden, 36% fewer prostate cancer cases were registered, much more of them were pronounced in men above age 75 years (down 51%) than in men below age 70 (down 28%) while there was no decrease in the number of radical prostatectomies and an increase in radical radiotherapy.[23]

When analyzing the late-pandemic (June to December 2020) data from a database based on all US states and the District of Columbia, the average monthly number of prostate-specific antigen (PSA) showed a 36.4% decrease with a rebound to a 3.9% increase in late-pandemic and the average monthly number of prostate biopsy results saw a 37.9% decrease with a rebound to an 18.1% increase.[24] While in Australia, there was a reduction in PSA tests and general practitioner attendance in 2020 compared to 2019, but no reduction in multi-parametric MRI, prostate biopsy, nor number of radical prostatectomies or fiducial marker implantations.[25] Another long-term study in Australia estimated 14% fewer PSA tests, 12% fewer biopsies and 16% fewer prostatectomies on average, while steep decreases in PSA tests were observed during the first, second, and delta wave.[26] In an evaluation during the term of a year of the COVID-19 pandemic, the number of clinical visits, prostate biopsy, and men enrolled in active surveillance was significantly lower while the number of advanced and metastatic prostate cancer cases increased.[27] Also, there was an increase in open radical prostatectomies compared to laparoscopic approaches and an increase in external radiotherapy.[27] A study based on 286,609 patients with prostate cancer in the Mount Sinai Hospital System found that the overall hospitalization (64.91% for prostate cancer versus 47.34% for solid cancer; p-value <0.0001) and mortality rates (21.05% for prostate cancer versus 15.85% for solid cancer; p-value=0.0547) were higher in patients with prostate cancer and COVID-19 compared with those with solid cancers and COVID-19.[28]

Contrasting results were presented by two studies owing to racial disparity in prostate cancer care.[29, 30] Bernstein et al., 2021[30] suggested that black men were significantly less likely to undergo prostatectomy during the pandemic compared with white patients, despite similar conditions. While a study based on the Veterans Affairs Health Care System disputed that although prostate biopsy volume and diagnosis rates of prostate cancer decreased during the COVID-19 pandemic, there were no statistically significant changes noted by race.[29]

4. Conclusion

Our review illustrates the changes in prostate cancer diagnosis, treatment, and prognosis after the emergence of the COVID-19 pandemic. Furthermore, we conducted a review on topics recently being highlighted such as the protective role of androgen deprivation therapy on SARS-CoV-2 infection, vaccination and immune response in patients with prostate cancer, and the outcomes of altered treatment plans. Identifying the changes in research and clinical practice of patients with prostate cancer worldwide is essential in providing appropriate patient care in today’s rapidly changing circumstances.

Capsule Summary

This review summarizes cutting-edge topics being highlighted which include the protective role of androgen deprivation therapy on SARS-CoV-2 infection, vaccination and immune response in patients with prostate cancer, and the outcomes of altered treatment plans.

Acknowledgements

All authors state that they have no actual or potential conflict of interest including any financial, personal, or other relationships with other people or organizations.

Author Contribution

All authors made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted.

Funding

None provided financial support for the conduct of the research and/or preparation of the article.

Conflicts of Interest

The authors have no conflicts of interest to declare for this study.

Provenance and peer review

Not commissioned; externally peer reviewed.

References

1.

Kim SY, Yeniova AÖ. Global, regional, and national incidence and mortality of COVID-19 in 237 countries and territories, January 2022: a systematic analysis for World Health Organization COVID-19 Dashboard. Life Cycle. 2022; 2e10

2.

Al-Quteimat OM, Amer AM. The impact of the COVID-19 pandemic on cancer patients. Am J Clin Oncol. 2020; 43(6):452-5

3.

Turco F, Armstrong A, Attard G, Beer TM, Beltran H, Bjartell A, et al. What experts think about prostate cancer management during the COVID-19 pandemic: Report from the Advanced Prostate Cancer Consensus Conference 2021. Eur Urol. 2022; S0302-2838(22):01650-5

4.

Bhowmick NA, Oft J, Dorff T, Pal S, Agarwal N, Figlin RA, et al. COVID-19 and androgen-targeted therapy for prostate cancer patients. Endocr Relat Cancer. 2020; 27(9):R281-R92

5.

Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020; 31(8):1040-5

6.

Gedeborg R, Lindhagen L, Loeb S, Styrke J, Garmo H, Stattin P. Androgen deprivation therapy, comorbidity, cancer stage and mortality from COVID-19 in men with prostate cancer. Scand J Urol. 2022; 56(2):104-11

7.

Gedeborg R, Styrke J, Loeb S, Garmo H, Stattin P. Androgen deprivation therapy and excess mortality in men with prostate cancer during the initial phase of the COVID-19 pandemic. PLoS One. 2021; 16(10)e0255966

8.

Klein EA, Li J, Milinovich A, Schold JD, Sharifi N, Kattan MW, et al. Androgen deprivation therapy in men with prostate cancer does not affect risk of infection with SARS-CoV-2. J Urol. 2021; 205(2):441-3

9.

Jiménez-Alcaide E, García-Fuentes C, Hernández V, De la Peña E, Pérez-Fernández E, Castro A, et al. Influence of androgen deprivation therapy on the severity of COVID-19 in prostate cancer patients. Prostate. 2021; 81(16):1349-54

10.

Koskinen M, Carpen O, Honkanen V, Seppänen MRJ, Miettinen PJ, Tuominen JA, et al. Androgen deprivation and SARS-CoV-2 in men with prostate cancer. Ann Oncol. 2020; 31(10):1417-8

11.

Schmidt AL, Tucker MD, Bakouny Z, Labaki C, Hsu CY, Shyr Y, et al. Association between androgen deprivation therapy and mortality among patients with prostate cancer and COVID-19. JAMA Netw Open. 2021; 4(11)e2134330

12.

Kwon DH, Vashisht R, Borno HT, Aggarwal RR, Small EJ, Butte AJ, et al. Androgen-deprivation therapy and SARS-CoV-2 in men with prostate cancer: findings from the University of California Health System registry. Ann Oncol. 2021; 32(5):678-9

13.

Duarte MBO, Leal F, Argenton JLP, Carvalheira JBC. Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: a propensity score-based analysis. Infect Agent Cancer. 2021; 16(1):66

14.

Zhang L, Zhu F, Xie L, Wang C, Wang J, Chen R, et al. Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China. Annals of oncology: Official Journal of the European Society for Medical Oncology. 2020; 31(7):894-901

15.

Sari Motlagh R, Abufaraj M, Karakiewicz PI, Rajwa P, Mori K, Mun DH, et al. Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis. World J Urol. 2022; 40(4):907-14

16.

Stroman L, Cathcart P, Lamb A, Challacombe B, Popert R. A cross-section of UK prostate cancer diagnostics during the coronavirus disease 2019 (COVID-19) era - a shifting paradigm?. BJU Int. 2021; 127(1):30-4

17.

Grummet J, Gorin MA, Popert R, O’Brien T, Lamb AD, Hadaschik B, et al. “TREXIT 2020”: why the time to abandon transrectal prostate biopsy starts now. Prostate Cancer and Prostatic Diseases. 2020; 23(1):62-5

18.

Surasi DSS, Wang X, Bathala TK, Hwang H, Arora S, Westphalen AC, et al. The impact and collateral damage of COVID-19 on prostate MRI and guided biopsy operations: Society of abdominal radiology prostate cancer disease-focused panel survey analysis. Abdom Radiol (NY). 2021; 46(9):4362-9

19.

Ferrari A, Sanchis-Gomar F, Mattiuzzi C, Henry BM, Lippi G. Is COVID-19 impacting prostate cancer screening? A survey of prostate-specific antigen test requests during a local outbreak. Ejifcc. 2021; 32(1):69-77

20.

Sciarra A, Salciccia S, Maggi M, Del Giudice F, Busetto GM, Musio D, et al. Elective procedures for prostate cancer in the time of Covid-19: a multidisciplinary team experience. Prostate Cancer Prostatic Dis. 2020; :1-3

21.

Nossiter J, Morris M, Parry MG, Sujenthiran A, Cathcart P, van der Meulen J, et al. Impact of the COVID-19 pandemic on the diagnosis and treatment of men with prostate cancer. BJU Int. 2022

22.

Deukeren DV, Heesterman BL, Roelofs L, Kiemeney LA, Witjes JA, Smilde TJ, et al. Impact of the COVID-19 outbreak on prostate cancer care in the Netherlands. Cancer Treat Res Commun. 2022; 31:100553

23.

Fallara G, Sandin F, Styrke J, Carlsson S, Lissbrant IF, Ahlgren J, et al. Prostate cancer diagnosis, staging, and treatment in Sweden during the first phase of the COVID-19 pandemic. Scand J Urol. 2021; 55(3):184-91

24.

Kaufman HW, Chen Z, Niles JK, Radcliff J, Fesko Y. Patterns of prostate-specific antigen testing and prostate biopsies during the COVID-19 pandemic. JCO Clin Cancer Inform. 2021; 5:1028-33

25.

Ip CCK, Kealey J, Davis ID, Sengupta S. Impacts of the COVID-19 pandemic on early detection of prostate cancer in Australia. BJU Int. 2021; 128(Suppl 3):6-8

26.

Papa N, Roberts MJ, Perera M. The continuing impacts of the COVID-19 pandemic on diagnosis and surgical prostate cancer management: a population-based analysis. ANZ J Surg. 2022

27.

Pepe P, Pepe L, Pennisi M, Fraggetta F. Prostate cancer diagnosis and management during one year of the COVID-19 pandemic. Anticancer Res. 2021; 41(6):3127-30

28.

Chakravarty D, Ratnani P, Sobotka S, Lundon D, Wiklund P, Nair SS, et al. Increased hospitalization and mortality from COVID-19 in prostate cancer patients. Cancers (Basel). 2021; 13(7)

29.

Klaassen Z, Stock S, Waller J, De Hoedt A, Freedland SJ. Association of the COVID-19 pandemic with rates of prostate cancer biopsies and diagnoses in black vs white US Veterans. JAMA Oncology. 2022

30.

Bernstein AN, Talwar R, Handorf E, Syed K, Danella J, Ginzburg S, et al. Assessment of prostate cancer treatment among black and white patients during the COVID-19 pandemic. JAMA Oncol. 2021; 7(10):1467-73

31.

Zattoni F, Marra G, Kretschmer A, Preisser F, Tilki D, Kesch C, et al. Has the COVID-19 outbreak changed the way we are treating prostate cancer? An EAU - YAU prostate cancer working group multi-institutional study. Cent European J Urol. 2021; 74(3):362-5

32.

Ginsburg KB, Curtis GL, Timar RE, George AK, Cher ML. Delayed radical prostatectomy is not associated with adverse oncologic outcomes: Implications for men experiencing surgical delay due to the COVID-19 pandemic. J Urol. 2020; 204(4):720-5

33.

Chan VW, Tan WS, Asif A, Ng A, Gbolahan O, Dinneen E, et al. Effects of delayed radical prostatectomy and active surveillance on localised prostate cancer-a systematic review and meta-analysis. Cancers (Basel). 2021; 13(13)

34.

Kizilkan Y, Senel S, Ozercan AY, Balci M, Eroglu U, Aktas BK, et al. Evaluating the anxiety and depression status of prostate cancer patients whose operations were postponed because of the COVID-19 pandemic. Int J Clin Pract. 2021; 75(8)e14278

35.

Araújo N, Costa A, Lopes-Conceição L, Ferreira A, Carneiro F, Oliveira J, et al. Androgen-deprivation therapy and cognitive decline in the NEON-PC prospective study during the COVID-19 pandemic. ESMO Open. 2022; 7(2):100448

36.

Taborska P, Strizova Z, Stakheev D, Sojka L, Bartunkova J, Smrz D. CD4(+) T cells of prostate cancer patients have decreased immune responses to antigens derived from SARS-CoV-2 spike glycoprotein. Front Immunol. 2021; 12:629102

37.

Liontos M, Terpos E, Kunadis E, Zagouri F, Briasoulis A, Skafida E, et al. Treatment with abiraterone or enzalutamide does not impair immunological response to COVID-19 vaccination in prostate cancer patients. Prostate Cancer Prostatic Dis. 2021; :1-2

38.

Fujiwara M, Yuasa T, Komai Y, Fujiwara R, Oguchi T, Numao N, et al. Switching patients with prostate cancer from GnRH antagonist to long-acting LHRH agonist for androgen deprivation: reducing hospital visits during the coronavirus pandemic. Cancer Diagn Progn. 2021; 1(1):1-5

39.

Gedeborg R, Lindhagen L, Loeb S, Styrke J, Garmo H, Stattin P. Androgen deprivation therapy, comorbidity, cancer stage and mortality from COVID-19 in men with prostate cancer. Scand J Urol. 2021; :1-8

40.

Karimi A, Nowroozi A, Alilou S, Amini E. Effects of androgen deprivation therapy on COVID-19 in patients with prostate cancer: a systematic review and meta-analysis. Urol J. 2021; 18(6):577-84

41.

Caffo O, Zagonel V, Baldessari C, Berruti A, Bortolus R, Buti S, et al. On the relationship between androgen-deprivation therapy for prostate cancer and risk of infection by SARS-CoV-2. Ann Oncol. 2020; 31(10):1415-6

42.

Barrett R, Barrett R, Dhar K, Birch B. Gonadorelins adherence in prostate cancer: A time-series analysis of England’s national prescriptions during the COVID-19 pandemic (from Jan 2019 to Oct 2020). BJUI Compass. 2021

43.

Lee MC, Erickson TR, Stock S, Howard LE, De Hoedt AM, Amling CL, et al. Association between delay to radical prostatectomy and clinically meaningful outcomes among patients with intermediate and high-risk localized prostate cancer. J Urol. 2022; 207(3):592-600

44.

Diamand R, Ploussard G, Roumiguié M, Oderda M, Benamran D, Fiard G, et al. Timing and delay of radical prostatectomy do not lead to adverse oncologic outcomes: results from a large European cohort at the times of COVID-19 pandemic. World J Urol. 2021; 39(6):1789-96

45.

Loeb S, Mihalcea R, Perez-Rosas V, Xu A, Taylor J, Byrne N, et al. Leveraging social media as a thermometer to gauge patient and caregiver concerns: COVID-19 and prostate cancer. Eur Urol Open Sci. 2021; 25:1-4

46.

Irusen H, Burger H, Fernandez PW, Esterhuizen T, Suliman S, Seedat S. COVID-19 related anxiety in men with localized prostate cancer at tertiary hospitals in cape town, South Africa. Cancer Control. 2021; 28:10732748211024239

47.

Lopez P, Taaffe DR, Newton RU, Spry N, Shannon T, Frydenberg M, et al. Can exercise adaptations be maintained in men with prostate cancer following supervised programmes? implications to the COVID-19 landscape of urology and clinical exercise. Eur Urol Open Sci. 2020; 21:47-50

48.

Notohamiprodjo S, Eiber M, Lohrmann C, Weber WA. Temporary reactive response of axillary lymph nodes to COVID-19 vaccination on (18)F-rhPSMA-7.3 PET/CT in patients with prostate cancer. J Nucl Med. 2022