Archive for category: BJUI Blog

Coming out of lockdown safely – A view from New Zealand

How our lives have changed. Over two months ago we published a popular blog on the effect of COVID-19 on our surgical practice (https://www.bjuinternational.com/bjui-blog/covid-19-and-urology/). In many ways it informed us as to what to do during challenging times to keep our patients safe.

As we gradually take careful steps out of lockdown, our minds are focused on the most important of all words – SAFETY. 

While every nation will have differences and nuances, the principles of learning from each other, remain the same as they did when lockdowns started.

I am not surprised by new and ever changing information about the disease almost every day and see international collaboration as a powerful and positive tool in this situation.

With this in mind I requested our friends from Italy, China, Germany and New Zealand for their own perspectives.

Here are their thoughts for your reading pleasure.

Please feel free to insert your comments under the blog and share on social media.

Yours in friendship,
Prokar Dasgupta
Editor in Chief, BJUI

It is hard to believe that 9 weeks ago as USANZ President the ASM was cancelled, due to the impending wave that was the Covid-19 global pandemic. Health and safety, reputation and finances were considered, in that order. USANZ 2020 ASM was the first major medical conference cancelled – others followed lockstep. There was no blueprint for this global black-swan event!

On our return to New Zealand an island country of 5 million, where 60% of health care is delivered via the public health “free for all” system, the remainder in the private sector. Our visionary Prime Minister, Jacinda Ardern initiated a “go-hard go-early” level 4 lockdown with only essential services open – elimination was the goal.

We were all un-prepared, and it lasted 5 weeks. A surgical pause in both health sectors allowed planning, preparation and training in PPE for the disease surge that did not arrive. We zoomed in our pyjamas and made sure we were free for the 1pm daily national television briefings featuring Jacinda Ardern and Ashley Bloomfield, DG of health, who has achieved cult status, and now features on a range of t-shirts. Cell phone tracking data indicated over 90% reduction in movement. Our “team of 5 million” has been a large part of the evolving success story. Elimination was possible, is possible and was confirmed! During this time manual contact tracing was expanded, testing snowballed, and Covid cases fell to zero.

During level 4 we undertook only non-deferrable surgical cases, with case definitions agreed by all specialties. We lost only 10% of our theatre volumes. OPD were completed by phone or video, and only patients that needed a procedure were seen face to face. Medically we have had no actual Covid cases in the surgical service, a handful of Covid patients in ICUs nationally. The majority of deaths did not reach ICU due to their age and co-morbidity.

We have now welcomed stepdown, level 2 with open arms, although concerned about a second wave of cases, however our unquestionable advantage of living in this unique country – our island fortress with a salt-water moat – sees us optimistic. We’re adjusting to sign in manually to all retail premises in light of no electronic tracing App and 80% of our businesses are open with the exception of bars, gatherings are restricted, and our hard borders remain.

Currently we enter the hospital via a staff entrance, with hand sanitiser but no masks. Patients are allowed 1 visitor only and have to sign in, use hand sanitiser and have restricted duration of visit. Normal surgical volumes have now resumed with no restrictions on the type of cases allowed.

We are advised to stay home if we have any respiratory symptoms, get a swab and cancel activity – no more kiwi grit or soldiering on! Patients are screened 7 days pre op by a phone call, delayed if international travel or a Covid contact within 14 days. A swab is only recommended if the patient is symptomatic, and if negative surgery can be completed. Patients are cancelled on the day of admission if they are unwell. Cancellations are now acceptable. A 20% operating theatre throughput reduction has been observed. We feel lucky, for now. From a USANZ perspective we are looking into innovative virtual meeting formats along with cancelling or postponing all face to face meetings.

Our international borders remain hard with a 14-day voluntary lockdown for all incoming. This will be in place until a successful vaccine is available. We accept international isolation will be in place for a while and hope to enjoy this pause, while implementing any useful learned strategies. We are proud of our inspirational leader, intelligent government and unprecedented international success – at least up until now. We wait, watch, listen and hold our breath… remember we are all in this together!

Stephen Mark, USANZ President

Coming out of lockdown safely – A view from Italy

How our lives have changed. Over two months ago we published a popular blog on the effect of COVID-19 on our surgical practice (https://www.bjuinternational.com/bjui-blog/covid-19-and-urology/). In many ways it informed us as to what to do during challenging times to keep our patients safe.

As we gradually take careful steps out of lockdown, our minds are focused on the most important of all words – SAFETY. 

While every nation will have differences and nuances, the principles of learning from each other, remain the same as they did when lockdowns started.

I am not surprised by new and ever changing information about the disease almost every day and see international collaboration as a powerful and positive tool in this situation.

With this in mind I requested our friends from Italy, China, Germany and New Zealand for their own perspectives.

Here are their thoughts for your reading pleasure.

Please feel free to insert your comments under the blog and share on social media.

Yours in friendship,
Prokar Dasgupta
Editor in Chief, BJUI

I am grateful to BJU International for having had the opportunity, around 2 months ago, to share my perspective on the impact of the COVID-19 pandemic on urological practice at Careggi University Hospital in Florence, Italy. I hope that information, coming from an Italian Centre that had to timely re-organize its logistics and surgical schedule in light of the rapid spread of the epidemic across the Country, might have provided some insights for urologists in the UK and worldwide to adapt their own activity during the acute phase of the COVID-19 outbreak.

Herein I am honored to share with you my perspective on how we may safely come out of lockdown, and on what we may learn as a Community from the COVID-19 pandemic to optimize the future organization of urological services. 

First of all, I entirely endorse Prof. Dasgupta’s view that, while the way Urology Centres around the world are coping with the challenges raised by the COVID-19 pandemic, as well as the way they are trying to rebuild new “standards” during the “second phase” of the emergency, will certainly vary within Countries, Regions and Hospitals, we as urologists should be open-minded and strive to share and learn as much as possible from each other. As such, in the highly complex scenario we are all living in, every perspective and viewpoint should be leveraged to set new tiles in the “mosaic” of evidence on Urology practice in the post-COVID era.

The status of the COVID-19 epidemic in Italy has significantly changed through the last two months. As of 15th March 2020, the number of laboratory-confirmed cases in Italy was 24 747, with 1809 deaths. As of 14th May 2020, these numbers were 223 096 and 31 368, respectively (making Italy the fifth Country in the world with the higher number of infections, https://lab24.ilsole24ore.com/coronavirus/).

Fortunately, the measures undertaken by the Italian Government so far, including the lockdown, have led to a drastic reduction in the number of daily infections and deaths due to COVID-19, with a progressive parallel decrease in the burden of severely ill patients admitted in ICUs.

However, there is no doubt that this unprecedented pandemic has had a dramatic impact on Italy from all possible standpoints, including the healthcare system. In particular, urology practice has been truly revolutionized during the past two months. Indeed, not only virtually all Centres worldwide have been forced to follow strict schemes for the triage of urological procedures that should have been prioritized in light of the scarcity of resources [1-3], but also Urology training programs have suffered a significant slowdown with potential meaningful consequences on residents’ learning curve [4,5]. As such, while we are now facing the new challenge of dealing with the “adaptation” and forthcoming “chronic” phases of the pandemic (during which all urological services will be progressively reopened to patients) we should keep the focus on preventing nosocomial infection and on cost-effective use of available resources.

In this scenario, the Department of Urology of Careggi University Hospital, directed by Prof. Carini and Prof. Serni, located in Tuscany – one of the five Italian Regions that have been hit most by COVID-19 – has already planned a series of measures aiming to safely restart all Urology services in the coming weeks, ensuring patients and healthcare workers’ safety.

  • First, since late March, all patients scheduled for urological procedures (as well as patients undergoing minor surgeries in the outpatient setting, ESWL and prostatic biopsies) had to be tested for Sars-CoV-2 infection (through nasopharyngeal swaps) 48 hours before surgery. Patients who resulted positive for COVID-19 were recommended to remain in quarantine until two consecutive nasopharyngeal swaps resulted negative for the infection. Then, they could have been rescheduled for surgery. In addition, starting from May 1st 2020, all patients undergoing surgery were tested for Sars-CoV-2 infection through nasopharyngeal swaps 24-48 hours before discharge from the Hospital. Of note, patients’ relatives were not allowed to enter the Department during the whole hospitalization period; as such, the news regarding both the intervention and the postoperative course were communicated by the urologists in charge of the inpatient ward by telephone.
  • Second, beyond appropriate use of all PPE, all healthcare workers in our Department, including nurses, doctors and administrative staff, underwent serology testing (IgM, IgG) for Sars-CoV-2 infection during the first weeks of April. Those who resulted positive according to the serology underwent further testing with two consecutive nasopharyngeal swaps; if positive, they were recommended to remain in quarantine until two consecutive nasopharyngeal swaps resulted negative for the infection.
  • Regarding the Urology operating rooms, we are currently using 50% of them (two out of four) in the main Hospital pavilion, prioritizing major uro-oncological surgery (open and minimally-invasive procedures for prostate, urothelial, and kidney cancer), as well as surgery for penile and testicular cancer. Most endoscopic surgeries for bladder cancer (TURBs) were redeployed in a different Hospital pavilion (in one dedicated operating theater, active four days a week). Overall, the surgical activity of our Urology Department is currently reduced by 20-25% as compared to a “standard” period. Fortunately, we are not facing major concerns regarding the availability of ICU beds for urological patients at our Hospital.

While in the very first weeks after the spread of the epidemic, only high-priority major uro-oncological surgeries (i.e. radical cystectomy, radical prostatectomy for locally-advanced diseases, nephrectomy for cT2+ cancers, radical nephroureterectomy for high-risk upper tract urothelial carcinoma) were performed – accounting for approximately one third of all major cancer surgeries at our Centre based on a recently published study by our group [6]) – later on we progressively included in the surgical schedule also lower-priority interventions (i.e. radical prostatectomy for intermediate-risk prostate cancer, radical/partial nephrectomy for cT1b tumors, etc.).

  • Similarly, we progressively reintroduced into the surgical schedules also elective interventions for benign urologic conditions, prioritizing those patients who were symptomatic and/or at higher risk of adverse clinical outcomes. It is important to highlight that the management of the surgical waiting list during the acute phase of the COVID-19 pandemic and the planning of the weekly surgical schedule was performed according to a careful day-by-day evaluation of the available resources in the Hospitals’ ICUs, as well as the number of available theaters for urological procedures.
  • Importantly, we did not record any case of COVID-19 after elective or urgent urological procedure during the past two months (including after minimally-invasive surgery, the safety of which has been object of great debate within the Urology Community [7]).
  • Regarding urological emergencies, patients who were admitted to our Urology Unit from the Accident & Emergency Department had to be tested for Sars-CoV-2 infection (through nasopharyngeal swaps) before admission. If needed, surgery for urological emergencies was performed in a dedicated operating theater in the main Urology pavilion.
  • The kidney transplantation program from deceased donors (both donors after brain death [DBD] and donors after circulatory death [DCD]) continued without major changes at our Unit, thanks to a timely and effective reorganization of all activites related to organ procurement by the Tuscany Transplant Authority, as well as a series of logistical and clinical measures implemented early after the spread of the epidemic to prevent transmission of the disease to KT recipients. On the contrary, kidney transplantation from living donors was (and is still) suspended since the end of February 2020.
  • Most urological procedures in the outpatient setting (ESWL, minor surgeries, prostatic biopsies) were canceled during the first weeks of the COVID-19 epidemic, being the only exception cystoscopies for suspected bladder cancer. Thereafter, they were progressively re-started (especially during the last 2 weeks), provided that patients had been tested negative for Sars-CoV-2 infection and anyway after a comprehensive triage by telephone outlining the priority of such procedure.
  • Finally, while during the “acute phase” of the pandemic the vast majority of urological consultations in the outpatient setting were canceled (and replaced by telemedicine strategies, except for those visits deemed urgent by urological staff after a careful screening by telephone interview and those for medications after elective surgery). In the coming weeks most of them will be re-started, provided adequate logistics (i.e. distancing between patients and appropriate time schedules) to ensure maximal safety for both patients and healthcare workers.

Overall, the “big picture” delineated by all these facts and figures highlights that our Unit, as in many other Departments in Italy, has already started the process of rebuilding the foundations of a new “routine” urological practice, adapting (and eventually overcoming) to the challenges met during the first acute phase of the COVID-19 emergency.

Nonetheless, my global perspective is that urologists should remain vigilant and resilient, keeping the focus on ensuring safety and cost-effective use of resources. This is important, as the COVID-19 epidemic could potentially flare-up in the near future if all safety measures recommended by Hospitals and the Government were not strictly followed by the population.

Moreover, I believe this unprecedented emergency scenario, which has profoundly revolutionized our healthcare system as well as our way of thinking and behaving, should be leveraged to understand which steps should be prioritized to move Urology forward from both clinical, logistical, educational and scientific perspectives.

In this view, the lessons we can learn as a Community from this pandemic for the future include:  

– the need for appropriate (evidence-based) selection of candidates for urological procedures, taking into account also patients’ values and expectations;

– careful prioritization of surgeries, based on the potential impact of delay on important patient outcomes [8];

– rational use of all available treatment modalities for urological cancers (including active surveillance), strengthening the value of team-work and developing a truly multidisciplinary spirit;

– refinement of surgical informed consents, tailoring them to such emergency scenarios [9];

– increased use of virtual Urology learning programs for education of residents [10];

– implementation of teleproctoring and telementoring technologies into everyday surgical practice [11];

– inclusion of telemedicine into routine pathways of care for urological patients [11].

By doing so, we may be able not only to be more prepared for similar future emergency scenarios, but also to take significant steps toward improvement of Urology as a specialty, as well as ourselves as individuals.

Riccardo Campi, MD

– Resident in Urology, Dept. of Urology, Careggi University Hospital, Florence (Italy)
– Ph.D. student, Doctoral Program in Clinical Sciences, Dept. of Experimental and Clinical Medicine, University of Florence, Florence (Italy)
– Member of the EAU Young Academic Urologists – Renal Cancer Working Group
– Associate Member of the EAU Section of Oncological Urology
– Twitter: @Ric_Campi

References

[1] Stensland KD, et al. Considerations in the Triage of Urologic Surgeries During the COVID-19 Pandemic. Eur Urol. 2020 doi: 10.1016/j.eururo.2020.03.027.

[2] Ribal MJ, et al. EAU Guidelines Office Rapid Reaction Group: An organisation-wide collaborative effort to adapt the EAU guidelines recommendations to the COVID-19 era. Eur Urol 2020 (In Press); available at: https://www.europeanurology.com/covid-19-resourceEAU

[3] Ahmed K, et al. Global challenges to urology practice during COVID‐19 pandemic. BJU Int 2020. In Press. https://doi.org/10.1111/bju.15082

[4] Amparore D, et al. Impact of the COVID-19 pandemic on urology residency training in Italy. Minerva Urol Nefrol. 2020. doi: 10.23736/S0393-2249.20.03868-0

[5] Porpiglia F, et al. Slowdown of urology residents’ learning curve during the COVID-19 emergency. BJU Int. 2020 [Epub ahead of print] doi: https://doi.org/10.1111/bju.15076.

[6] Campi R, et al. Assessing the Burden of Nondeferrable Major Uro-oncologic Surgery to Guide Prioritisation Strategies During the COVID-19 Pandemic: Insights from Three Italian High-volume Referral Centres. Eur Urol. 2020 [Epub ahead of print] doi:10.1016/j.eururo.2020.03.054

[7] Novara G, et al. Risk of SARS-CoV-2 Diffusion when Performing Minimally Invasive Surgery During the COVID-19 Pandemic. Eur Urol Apr 2020;0(0). Available at: https://www.europeanurology.com/article/S0302-2838(20)30247-5/abstract

[8] Wallis CJD, et al. Risks from Deferring Treatment for Genitourinary Cancers: A Collaborative Review to Aid Triage and Management During the COVID-19 Pandemic. Eur Urol 2020. In Press. DOI: https://doi.org/10.1016/j.eururo.2020.04.063

[9] Bryan AF, et al. Unknown unknowns: Surgical consent during the COVID-19 pandemic. Annals of Surgery 2020. In Press. https://journals.lww.com/annalsofsurgery/Documents/Unknown%20unknowns%20.pdf

[10] Claps F, et al. Smart Learning for Urology Residents during the COVID-19 pandemic and beyond: Insights from a Nationwide Survey in Italy. Minerva Urol Nefrol 2020. In Press.

[11] Karim JS, et al. Bolstering the surgical response to COVID‐19: how virtual technology will save lives and safeguard surgical practice. BJU Int 2020. In Press. https://doi.org/10.1111/bju.15080

[12] Connor MJ, et al. COVID‐19 pandemic – is virtual urology clinic the answer to keeping the cancer pathway moving? BJU Int 2020. In Press. https://doi.org/10.1111/bju.15061

 

COVID-19 and Prostate Cancer — Challenges and Solutions

The numbers are staggering. As of the date of this brief commentary, the World Health Organization has reported more than 4.6 million cases and upwards of 311,840 deaths worldwide from the COVID-19 pandemic. The virus responsible for the disease known as COVID-19, SARS-CoV-2, is highly infectious and the risks are clearly significant for nearly everyone. Nonetheless, the risk is much higher for some of us than for others. In particular, we have begun to understand the distinct risks faced by men with prostate cancer and the unique intersection of biological, health, and lifestyle factors in COVID-19 and prostate cancer. Although there is a great deal yet to be learned, there are indeed many aspects of the overlap between COVID-19 and prostate cancer that we have already been able to discern and which we have begun to address. Perhaps most striking, older men who are at greatest risk for prostate cancer may also be at greatest risk for COVID-19. 

New York City

Biology Makes a Difference – COVID-19 and prostate cancer share some common biological features. A gene responsible for male traits or characteristics, the androgen receptor, which is dysregulated or impaired in prostate cancer, is also important in COVID-19. Androgens can suppress the body’s immune response to infections and may explain the reason for higher rates of infection in men.  At the same time, a gene known as TMPRSS2 is also highly expressed in both COVID-19 and prostate cancer. In fact, these issues may be related—more androgens could signify greater expression of TMPRSS2 which could create greater susceptibility to the virus. These biological risks are compounded by a number of critical health conditions and lifestyle issues.

Common Risk Factors – Studies from around the world have shown that several chronic health conditions or comorbidities create greater risk for contracting the virus, becoming more severely ill, or dying from COVID-19. It is indeed concerning that many of these are the same risks we see in prostate cancer: hypertension, diabetes, COPD, and obesity. Prostate cancer patients with multiple comorbid conditions may be at even greater risk. Cancer patients in general have weakened immune systems which makes them more vulnerable to infectious disease, further compounding the unique factors affecting men with prostate cancer. Some of the lifestyle factors that may contribute to chronic health conditions also appear to be risk factors for COVID-19 infection, most importantly smoking and high levels of alcohol consumption. We are especially concerned about men who are active smokers, as smoking has been clearly linked to worse outcomes in men who have become ill with COVID-19. We believe that the guidance we generally offer to prostate cancer patients is as, if not more, relevant now in this time of the COVID pandemic—adopt healthy habits, including smoking cessation, a nutritious diet, exercise, and proper management of chronic conditions most notably diabetes.

Looking Ahead – As the pandemic evolves and we look to the future, we are focused on ways to prevent the spread of infection and to create viable treatments for those who become ill. Worldwide, more than nine million men currently face decisions about biopsy, active surveillance, surgery, radiation, hormonal therapy, or chemotherapy related to prostate cancer in the context of COVID-19 and another 3 million more will find themselves facing these decisions by the end of this year. We are working intensely to address their needs. More than 1,460 clinical trials are underway to test therapeutic interventions to treat COVID-19. What we have come to understand about the shared biology between COVID-19 and prostate cancer and common risk factors will be invaluable. We must learn everything we can about the ways in which the virus impacts lung function as it relates to prostate cancer—the respiratory symptoms that result from infection have been especially lethal—and continue to explore the role of androgens in response to new drugs. Many drugs originally intended and approved for other uses are being tested for potential “repurposing” and new drugs and vaccines are under investigation. New clinical guidelines have been established for the treatment of prostate cancer patients at risk of or for those who have contracted the virus, and these guidelines will continue to evolve and be updated.

A Global Perspective – It is critical that we understand the COVID-19 pandemic both on the level of individual experience and global impact. For prostate cancer patients, this means recognizing the way that biology, related chronic health conditions, and lifestyle choices come together to impact the risk of disease, disease severity, and outcomes. Prostate cancer patients and their doctors must come together to find the way forward during this time of unprecedented crisis and opportunities for improving outcomes and quality of life for prostate cancer patients.

Ash Tewari, Zach Dovey and Dimple Chakravarty

Residents’ Podcast: Efficacy of vibegron, a novel β3‐adrenoreceptor agonist, on severe UUI related to OAB

Part of the BURST/BJUI Podcast Series

Nikita Bhatt is a Specialist Trainee in Urology in the East of England Deanery and a BURST Committee member @BURSTUrology

Efficacy of vibegron, a novel β3‐adrenoreceptor agonist, on severe urgency urinary incontinence related to overactive bladder: post hoc analysis of a randomized, placebo‐controlled, double‐blind, comparative phase 3 study

Masaki Yoshida*, Masayuki Takeda, Momokazu Gotoh, Osamu Yokoyama§, Hidehiro Kakizaki, Satoru Takahashi**, Naoya Masumori††, Shinji Nagai‡‡ and Kazuyoshi Minemura‡‡

*Department of Urology, National Centre for Geriatrics and Gerontology, Obu, Department of Urology, University of Yamanashi, Graduate School of Medical Sciences, Kofu, Japan, Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, §Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Department of Renal and Urological Surgery, Asahikawa Medical University, Asahikawa, Japan, **Department of Urology, Nihon University School of Medicine, Tokyo, ††Department of Urology, Sapporo Medical University School of Medicine, Sapporo, and ‡‡Kyorin Pharmaceutical Co., Ltd., Tokyo, Japan

Abstract

Objective

To evaluate the efficacy of a novel and selective β3‐adrenoreceptor agonist vibegron on urgency urinary incontinence (UUI) in patients with overactive bladder (OAB). Follow us visaliaweddingstyle for more details .

Patients and Methods

post hoc analysis was performed in patients with UUI (>0 episodes/day) who were assigned to receive vibegron or placebo in a vibegron phase 3 study. Patients were subclassified into mild/moderate (>0 to <3 UUI episodes/day) or severe UUI (≥3 UUI episodes/day) subgroup. Changes from baseline in number of UUI episodes/day, in number of urgency episodes/day, and in voided volume/micturition were compared between the groups. The percentage of patients who became UUI‐free (‘diary‐dry’ rate) and the response rate (percentage of patients with scores 1 [feeling much better] or 2 [feeling better] assessed by the Patient Global Impression scale [PGI]) were evaluated.

Results

Changes in numbers of UUI episodes at week 12 in the vibegron 50 mg, vibegron 100 mg and placebo groups, respectively, were −1.35, −1.47 and −1.08 in all patients, −1.04, −1.13 and −0.89 in the mild/moderate UUI subgroup, and −2.95, −3.28 and −2.10 in the severe UUI subgroup. The changes were significant in the vibegron 50 and 100 mg groups vs placebo regardless of symptom severity. Change in number of urgency episodes/day was significant in the vibegron 100 mg group vs placebo in all patients and in both severity subgroups. In the vibegron 50 mg group, a significant change vs placebo was observed in all patients and in the mild/moderate UUI subgroup. Change in voided volume/micturition was significantly greater in the vibegron 50 and 100 mg groups vs placebo in all patients, as well as in the both severity subgroups. Diary‐dry rates in the vibegron 50 and 100 mg groups were significantly greater vs placebo in all patients and in the mild/moderate UUI subgroup. In the severe UUI subgroup, however, a significant difference was observed only in the vibegron 50 mg group. Response rates assessed by the PGI were significantly higher in the vibegron groups vs placebo in all patients and in the both severity subgroups. Vibegron administration, OAB duration ≤37 months, mean number of micturitions/day at baseline <12.0 and mean number of UUI episodes/day at baseline <3.0 were identified as factors significantly associated with normalization of UUI.

Conclusions

Vibegron, a novel β3‐adrenoreceptor agonist, significantly reduced the number of UUI episodes/day and significantly increased the voided volume/micturition in patients with OAB including those with severe UUI, with the response rate exceeding 50%. These results suggest that vibegron can be an effective therapeutic option for OAB patients with UUI.

Four Seasons – Spring 2020’s Top Reviewer

This month, BJUI continues the Four Seasons Peer Reviewer Award recognising the hard work and dedication of our peer reviewers. Each quarter the Editor and Editorial Team select an individual peer reviewer whose reviews over the last 3 months have stood out for their quality and timeliness.

 

The Spring 2020 Crown goes to Runzhuo Ma 

Runzhuo Ma is a research fellow in the Center for Robotic Simulation and Education (CRSE), Institute of Urology, at the University of Southern California. After finishing his MD at Peking University, he joined CRSE under the leadership of Dr. Andrew J. Hung and Dr. Inderbir Gill. His research interests include surgical assessment, surgical simulation, and studying the impact of surgical quality on patient outcomes in urologic cancers.

Residents’ Podcast: Pharmacological interventions for treating CPP

Part of the BURST/BJUI Podcast Series

Nikita Bhatt is a Specialist Trainee in Urology in the East of England Deanery and a BURST Committee member @BURSTUrology

 

Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review

Juan V.A. Franco*, Tarek Turk, Jae Hung Jung, Yu-Tian Xiao§, Stanislav Iakhno, Federico Ignacio Tirapegui**, Virginia Garrote†† and Valeria Vietto‡‡
 
*Argentine Cochrane Centre, Instituto Universitario Hospital Italiano, Buenos Aires, Argentina, Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic, Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea, §Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai,
China, University of Tromso, Tromsdalen, Norway, **Urology Division, Hospital Italiano de Buenos Aires, ††Biblioteca Central, Instituto Universitario Hospital Italiano, and ‡‡Family and Community Medicine Service, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
 

Abstract

Objective

To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Patients and Methods

We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression, however, this one can be easily handle using Observer’s CBD hemp flower.

Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram.

Results

We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Most of our comparisons included short‐term follow‐up information. The median age of the participants was 38 years. Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies. Many patients prefer using natural medicine like the best CBD oil list here on this site.

We found low‐ to very low‐quality evidence that α‐blockers may reduce prostatitis symptoms based on a reduction in National Institutes of Health – Chronic Prostatitis Symptom Index (NIH‐CPSI) scores of >2 (but <8) with an increased incidence of minor adverse events such as dizziness and hypotension. Moderate‐ to low‐quality evidence indicates that 5α‐reductase inhibitors, antibiotics, anti‐inflammatories, and phytotherapy probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. Intraprostatic botulinum toxin A (BTA) injection may cause a large reduction in prostatitis symptoms with procedure‐related adverse events (haematuria), but pelvic floor muscle BTA injection may not have the same effects (low‐quality evidence). Allopurinol may also be ineffective for reducing prostatitis symptoms (low‐quality evidence). We assessed a wide range of interventions involving traditional Chinese medicine; low‐quality evidence showed they may reduce prostatitis symptoms without an increased incidence in adverse events.

Moderate‐ to high‐quality evidence indicates that the following interventions may be ineffective for the reduction of prostatitis symptoms: anticholinergics, Escherichia coli lysate (OM‐89), pentosan, and pregabalin. Low‐ to very low‐quality evidence indicates that antidepressants and tanezumab may be ineffective for the reduction of prostatitis symptoms. Low‐quality evidence indicates that mepartricin and phosphodiesterase inhibitors may reduce prostatitis symptoms, without an increased incidence in adverse events.

Conclusions

Based on the findings of low‐ to very low‐quality evidence, this review found that some pharmacological interventions such as α‐blockers may reduce prostatitis symptoms with an increased incidence of minor adverse events such as dizziness and hypotension. Other interventions may cause a reduction in prostatitis symptoms without an increased incidence of adverse events while others were found to be ineffective.

Covid-19: Collection of urology papers

Following on from our blog and recent podcasts on how the corona virus (Covid-19) is affecting urological operations in three countries: Italy, China and South Korea, we have put together a collection of the latest BJUI-published articles on the topic.

The first article by Connor and coworkers from Imperial Prostate discusses the potential costs to cancer patients if outpatient activity is cancelled by NHS trusts in order to free up resources for Covid-19 patients. They recommend that a virtual clinic consultation takes place in the first instance. So, what is life like in Isreal under COVID-19? Mostly quiet and a little surreal. In other words, very much like it is here. Israel was very aggressive in its early efforts to combat the spread of the virus, taking immediate measures to limit public gatherings, closing all non-essential businesses, and cancelling almost every major event in the country. Extreme yes, but also very safe.

The second article is by Ahmed, Hayat and Dasgupta from King’s Health Partners, London UK and discusses the national situation as of the end of March 2020: all non-urgent elective surgical procedures have been put on hold for three months to free up hospital beds and theatre staff; the discharge process for surgical inpatients has been accelerated and staff are being redeployed from non-essential services. But what impact will this have on the mental health of those patients missing out on treatment for their infertility or incontinence? And how are conditions categorized? The Cleveland Clinic Urology department has developed a five-point scale to aid in risk-stratifying patients – the following table is a more general version.

Surgical ProcedureSummary of Impact of COVID-19 on selected Urological procedures
Endoscopic/Outpatient procedures Diagnostic work should be avoided where possible, only emergency procedures under local anesthetic ideally.  Only urgent outpatient procedures should be carried out, these include biopsies of the prostate, cystoscopies for suspected bladder malignancy or hematuria.
Open/Laparoscopic   -Only urgent procedures, assessment for COVID-19 should be carried out, reduce chances of the need for post-surgery critical care. Full personal protection equipment should be worn. Urgent procedures may include trauma, ureteric stones, torsion and high-risk cancer patients
-The safety of carrying out laparoscopic work remains undetermined 
-The merits of local versus general anesthetic should be considered on a case by case basis if applicable 
Selected points on general theatre safety -The number of staff in theatre should be minimised and all must wear personal protective equipment in full with visors
-Positive pressurisation should be put on hold in theatre during a procedure and only 20 minutes after the patient has left the theatre, should it be restarted
– Need for COVID 19 testing of the patients and the clinical team prior to the procedure

Table 1. Adapted from RCS Intercollegiate General Surgery Guidance on COVID-19 (https://www.rcseng.ac.uk/coronavirus/joint-guidance-for-surgeons-v2/) and BJUI “COVID-19 and Urology” blog. 

Again, the idea of virtual clinics is raised as is the future training of medical and surgical students to enable them to be quickly deployed in the case of another pandemic, and a suggestion for parallel healthcare systems.

Testing, of course, is also of paramount importance.

 

In a comprehensive review of the situation as of the end of March 2020, Bernardo Rocco and co-workers describe what we know about the SARS-CoV-2 virus so far and what has been done, at least within Europe, to cope with the pandemic.  

It is thought that kidney cells are particularly prone to invasion by the virus, as evidenced by the numbers of kidney dysfunction in COVID-19 patients, and this may be due to the presence of angiotensin-converting 2 enzyme receptors on a small percentage (2-4%) of these cells to which the SARS-CoV-2 virus has an affinity.

The article further discusses the situation for medical students, transplant clinics and oncology, focussing on China, Italy and the UK. It also outlines extra precautions to take to limit virus transmission given the unknowns about its presence in blood, urine and faeces.

Returning to the subject of medical students, in particular in Italy, this paper by Porpiglia and coworkers explains that residents are unable to practise as the areas in which they usually work have been suspended (benign pathologies, lower urinary tract surgery and andrology), as have case meetings and outpatient clinics, and major surgery is being carried out by senior colleagues. Alternative teaching methods, via video link, are being introduced, e.g. surgeryinmotion-school.org, a well-established website showing recorded and live surgeries. The use of webinars for presentation of cases and social media, such as Twitter’s Journal Club, allow discussions to take place. Daily staff meetings can also take place via the web.

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safe way.

Cowbells and conundrums – the 3rd Advanced Prostate Cancer Consensus Conference

by Professor Declan G Murphy

Urologist & Director of Genitourinary Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia

Twitter: @declangmurphy

The 3rd Advanced Prostate Cancer Consensus Conference (APCCC) took place in Basel in late August 2019, and the subsequent manuscript was published in European Urology just recently. We delayed posting this blog until now as the recommendations were under embargo until the manuscript went online. As with the previous two APCCC events (which took place in St Gallen; the so-called “St Gallen meetings”), this “Basel meeting” and its resultant recommendations are certain to provoke discussion due to the contentious nature of the topics which feature. Indeed, much of the raison d’etre of the meeting is to create recommendations from key opinion leaders to help guide decision-making in prostate cancer, particularly in areas where confusion exists, and where traditional guidelines are not clear.

The format is as follows:

  • The meeting takes place every two years and includes two full days of plenary sessions from world leaders, and one half-day of voting to try and achieve consensus on hot topics
  • 72 of the world’s leading experts in prostate cancer are invited to deliver plenary addresses, and more than 750 delegates from 65 different countries
  • Ten areas of controversy are featured in the plenary sessions, and invited experts participate in a live vote on the final day to see if consensus can be reached. More than 120 questions are selected by the panel over the previous few months.
  • The level of consensus was defined as follows: answer options with 75% agreement were considered consensus, and answer options with 90% agreement were considered strong consensus.
  • The results are published in a detailed manuscript (40 pages!) in European Urology

The meeting is convened by Dr Silke Gillessen and Dr Aurelius Omlin who are world-renowned experts in prostate cancer. One of the unique and most enjoyable aspects of the APCCC is the unashamed Swiss-ness which Silke and Aurelius bring to the meeting. The meeting is conducted in a very relaxed manner with excellent interaction between the Faculty which is part of the high value of the meeting. Of course, one would expect a meeting in Switzerland to run efficiently, and Silke and Aurelius wield a goat’s bell for the one minute warning; if you hear the cow bell, then the time is up!

 

As before, the invited panel is a truly global gathering of world experts in prostate cancer:


A truly global gathering of world leaders in prostate cancer

The ten areas of controversy for #APCCC19 are as listed below, followed by a summary of some of the notable areas of consensus, along with some areas of non-consensus.

  1. Locally advanced prostate cancer
  2. Biochemical recurrence of prostate cancer after local therapy
  3. Management of the primary tumour in the metastatic setting
  4. Management of newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), including oligometastatic prostate cancer
  5. Management of nonmetastatic (M0) castration-resistant prostate cancer (CRPC)
  6. Management of metastatic CRPC (mCRPC)
  7. Bone health and bone metastases
  8. Molecular characterisation of tissue and blood
  9. Interpatient heterogeneity
  10. Side effects of hormonal treatments and their management

It was interesting to note the proportion of voting panellists by discipline as listed below, in particular the healthy proportion of urologists in a meeting focussed on advanced prostate cancer:

And also by region as listed below.

Obviously a massive amount of territory gets covered during this meeting, but I have highlighted some of the key recommendations within each of the ten areas of controversy below:

Locally advanced prostate cancer:

This section featured plenary addresses on node-positive prostate cancer from myself and radiation oncologist Dr Mack Roach. There was strong consensus that some sort of loco-regional treatment with surgery or radiation (RT) should be offered to men with node-positive prostate cancer, combined with androgen deprivation therapy (ADT) for men undergoing RT. The impact of PSMA PET/CT in defining N1 disease was considered and was recommended for accurate staging (pending the read out of the proPSMA trial which had not yet been published). Regarding duration of ADT, there was no consensus with answers ranging from six months to three years.

Biochemical recurrence (BCR) of prostate cancer after local therapy:

One of the stand-out themes of this year’s APCCC was the impact of PSMA PET/CT for imaging prostate cancer, and Lu-PSMA theranostics as a treatment for mCRPC. I am pleased to say that much of the focus of this was on data from here in Australia, and there was much favourable comment on how Australia has led in this area. It is fair to say there was a reasonable amount of envy also for how much access we have to PSMA PET/CT compared to many other parts of the world. In one of the opening plenaries, Professor Ian Davis did a terrific job overviewing this, and did introduce some cautionary tones about the management impact of novel imaging.

There was consensus that PSMA PET/CT should be used for the assessment of BCR following radiation or surgery. This is a new recommendation compared with the previous meeting, and is in line with the most recent EAU Prostate Cancer Guidelines. What PSA level should we image at? Most discussion centred around a PSA of 0.2ng/mL or greater following surgery.

For patients undergoing salvage RT, there was consensus that this should be accompanied by a short period (4-12 months) of ADT. 83% of panellists voted in favour of offering salvage RT before PSA reaches 0.5ng/mL, with 37% offering RT before PSA reaches 0.2ng/mL. There was consensus that ADT alone should not be used for the majority of patients with rising PSA and no evidence of metastases following prior local therapy.

Management of the primary tumour in the metastatic setting

This was certainly a hot topic. There was much discussion around the role of RT to the primary in men presenting with metastatic prostate cancer (in addition to lifelong ADT), and the most recent data from STAMPEDE led to a strong (98%) consensus for the use of RT in men presenting with low-volume metastatic prostate cancer. Volume was defined based on conventional imaging using classic CHAARTED criteria. The recommended dose was 55Gy over four weeks as per STAMPEDE.

Should we extrapolate from this data and offer surgery as local therapy in the same group of patients? There was 88% consensus that we SHOULD NOT offer surgery, other than within a clinical trial. There was also consensus that patients with N1 disease should be offered RT to the nodes in addition to the primary.

Management of newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), including oligometastatic prostate cancer

This is clearly one of the fastest moving areas in advanced prostate cancer and there was much new data to consider. The panellists reached consensus on 12 areas of mHSPC including:

  • Nomenclature – there was 77% consensus that we should avoid the term “castration”, although there was not consensus on what other term we should use! In describing treatment-naïve men, it is easy as we can use the term mHSPC. However, when treatment resistance emerges, we are still left with mCRPC (87% consensus).
  • I must say there was an outstanding intervention from patient advocate, Mr Millman, after the initial round of voting on this topic, saying how much patients detest the use of the term “castration”. I could not have agreed more. This led to the convenors calling for a repeat vote with subsequent vote in favour of avoiding the use of the term.
  • 95% consensus for obtaining histological evidence of prostate cancer in men suspected of having M1 disease; 96% consensus that ADT could be initiated prior to biopsy.
  • Most striking – 100% of panellists voted for ADT combined with something else (docetaxel or an androgen receptor (AR) pathway inhibitor) in patients with de novo high-volume mHSPC. There was much discussion about which combination should be offered, but there was no consensus. The decision can be individualised based on patient factors and local registration and reimbursement status. In Australia that means docetaxel for most patients while we awai tregistration/reimbursement for agents such as abiraterone, enzalutamide and apalutamide.
  • There was also consensus for combination approaches in men with de novo low-volume mHSPC, with 85% voting in favour of some additional systemic therapy in addition to ADT, and 80% supporting RT to the primary.
  • Similarly, in men with relapsing high-volume or low-volume mHSPC, there was consensus to offer combination systemic approaches, with no consensus on which therapy to offer in addition to ADT.
  • There was consensus (78%) that in men with mHSPC diagnosed with conventional imaging, that no additional imaging (ie PSMA PET/CT) should be utilised. That horse has already bolted in Australia where it is not unusual for men to be diagnosed with M1 disease using PSMA PET/CT in the first instance.

Regarding oligometastatic disease, there was consensus that if metastasis-directed therapy (MDT) is to be considered, that the extent and location of disease should not be defined using conventional imaging (79%), but should be defined using more sensitive imaging such as PSMA PET/CT (75%). There was also strong consensus that a distinction should be made between lymph node-only disease, and M1 disease involving other sites. Systemic therapy should be used in addition to local therapy to all local sites of disease (75%). I must say that I was pretty surprised that consensus was reached on this point, as guidelines still suggest that MDT approaches should still only be offered within clinical trials.

Management of nonmetastatic (M0) castration-resistant prostate cancer (CRPC)

What even is M0 CRPC? Once again, PSMA PET/CT dominated the conversation. Although there is a relatively recently accepted definition of high-risk M0 CRPC (castrate levels of testosterone; PSA doubling time of </= 10 months; M0 based on conventional imaging), it is fair to say that there was much interest in the role of PSMA PET/CT in this population of patients. Data about to be published at the time of the meeting reported that 98% of patients in this setting will have identifiable disease on PSMA PET/CT despite being M0/N0 on conventional imaging. There these patients are actually mCRPC, rather than M0 CRPC, albeit based on novel imaging with a lead-time bias. Nonetheless, following various overviews of the recent pivotal data showing improvements in metastasis-free survival (MFS, conventional imaging) in patients with M0 CRPC receiving enzalutamide, apalutamide or darolutamide, the panel voted 86% in favour of using one of these agents in this population of high-risk M0 CRPC. We also voted 86% in favour of NOT extrapolating this data to M0 CROC patients with PSA doubling time of greater than 10 months.

Management of metastatic CRPC (mCRPC)

Another huge area with much data to consider. Although much of this had been considered at the previous APCCC and indeed, there were many areas where consensus was not reached eg which agent to use for first-line mCRPC (docetaxel vs AR pathway inhibitor). Despite general enthusiasm for molecular profiling/precision medicine approaches (and some outstanding talks on these areas), there was 85% consensus that we should not use AR-V7 status when considering mCRPC patients for abiraterone or enzalutamide. There was consensus that a steroid dose of prednisone 5mg bd should be used when starting mCRPC patients on abiraterone, and an 86% consensus that a tapering course of steroids should be used when discontinuing abiraterone or docetaxel.

There was considerable interest in the role of reduced dose abiraterone (250mg with food, instead of 1000mg without food), based on a phase II study, and the panel voted 86% in favour of a reduced dose regimen when there are resource or patient constraints on receiving the full dose.

One of the standout talks of the meeting was delivered by Prof Michael Hofman on the role of Lu-PSMA in progressive mCRPC as he presented data from the phase II trial at Peter Mac published in Lancet Oncology (to date, the only prospective data on Lu-PSMA), and on the TheraP randomised controlled trial from Australia which will read out at ASCO in June this year. For patients with PSMA imaging-positive mCRPC who have exhausted approved treatments and cannot enrol in clinical trials, 43% of panellists voted for Lu-PSMA therapy in the majority of patients, and 46% voted for it in a minority of selected patients. For selecting patients for 177Lu-PSMA therapy, 64% of panellists voted for PSMA PET/CT plus FDG PET/CT with or without standard imaging, 21% voted for PSMA PET/CT plus standard imaging, and 15% voted for PSMA PET/CT alone. Although consensus was not reached on this issue, it was clear that the panel were very influenced by Michael’s excellent presentation on this topic, highlighting observations in the Peter Mac phase II trial that the use of FDG PET/CT in addition to PSMA PET/CT led to enhanced patient selection for Lu-PSMA therapy.

Bone health and bone metastases

There was 77% consensus in favour of routine screening for osteoporosis risk factors (e.g. current/history of smoking, corticosteroids, family history of hip fracture, personal history of fractures, rheumatoid arthritis, 3 alcohol units/day, and BMI), in patients with prostate cancer starting on long-term ADT. There was 86% consensus that mCRPC patients with predominantly bone disease and without visceral metastases, should be considered for radium-223 therapy, although this hardly applies to Australia where radium-223 is difficult to access and not reimbursed (plus Lu-PSMA available).

Molecular characterisation of tissue and blood

The plenaries on this topic were some of the most stimulating of the whole meeting. Truly outstanding talks from the pre-eminent leaders in the world. Among the consensus areas were:

  • 90% support for the assessment of germline BRCA1/2 status in M1 prostate cancer patients at some stage of the disease
  • 94% consensus that mismatch repair status (MSI high) should be assessed at some stage in M1 disease, most likely in mCRPC.
  • 96% consensus that PD-1 inhibition should be considered for MSI high patients at some stage in the disease course
  • Strong consensus (93%) for PARP inhibitor or platinum therapy at some point during the disease course in patients with a deleterious germline BRCA1/2 mutation
  • Genetic counselling and/or germline DNA testing for patients with newly diagnosed metastatic (M1) castration-sensitive/naïve prostate cancer: consensus (84%) for genetic counselling and/or germline DNA testing for the majority of patients with newly diagnosed metastatic prostate cancer.

Interpatient heterogeneity

There were some terrific talks on heterogeneity in prostate cancer, including ethnic and regional diversity, and the assessment and management of older patients. This year’s meeting expanded on this section compared to previously to acknowledge the diversity of prostate cancer around the world, and the fact that much of the data used to make recommendations is based on particular patient cohorts. The panel did reach consensus (76%) for the extrapolation of efficacy data to patients older than the majority of patients enrolled in a trial.

Side effects of hormonal treatments and their management

Professor Mark Frydenberg was one of the invited plenary speakers in this session and did a terrific job overviewing the management of hot flushes. I have not seen this topic discussed better anywhere in the world. There were also terrific talks on strategies to mitigate other side-effects. The panel reached strong consensus (94%) for the use of resistance and aerobic exercise to reduce fatigue in patients receiving systemic therapy for prostate cancer (apart from therapy dose reduction if possible).

Need more detail?

If you are interested in more detail, please download the manuscript from European Urology (open access), or visit Urotoday where the plenary lectures are available, along with exclusive interviews with many of the invited experts.

Finally, the 4th APCCC will take place from 7-9th October 2021. It will take place in the beautiful city of Lugano towards the Italian side of Switzerland. I encourage anyone with a strong interest in prostate cancer to consider attending. It will be a most stimulating and enjoyable few days immersed in the world of prostate cancer, and conducted with wonderful Swiss hospitality once again by the fabulous Silke Gillessen and Aurelius Omlin.

Residents’ podcast: the ProtecT trial

Mr Joseph Norris is a Specialty Registrar in Urology in the London Deanery. He is currently undertaking an MRC Doctoral Fellowship at UCL, under the supervision of Professor Mark Emberton. His research interest is prostate cancer that is inconspicuous on mpMRI. Joseph sits on the committee of the BURST Research Collaborative as the Treasurer and BSoT Representative.

The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression

Abstract

Objective

To test the hypothesis that the baseline clinico‐pathological features of the men with localized prostate cancer (PCa) included in the ProtecT (Prostate Testing for Cancer and Treatment) trial who progressed (n = 198) at a 10‐year median follow‐up were different from those of men with stable disease (n = 1409).

Patients and Methods

We stratified the study participants at baseline according to risk of progression using clinical disease stage, pathological grade and PSA level, using Cox proportional hazard models.

Results

The findings showed that 34% of participants (n = 505) had intermediate‐ or high‐risk PCa, and 66% (n = 973) had low‐risk PCa. Of 198 participants who progressed, 101 (51%) had baseline International Society of Urological Pathology Grade Group 1, 59 (30%) Grade Group 2, and 38 (19%) Grade Group 3 PCa, compared with 79%, 17% and 5%, respectively, for 1409 participants without progression (P < 0.001). In participants with progression, 38% and 62% had baseline low‐ and intermediate‐/high‐risk disease, compared with 69% and 31% of participants with stable disease (P < 0.001). Treatment received, age (65–69 vs 50–64 years), PSA level, Grade Group, clinical stage, risk group, number of positive cores, tumour length and perineural invasion were associated with time to progression (P ≤ 0.005). Men progressing after surgery (n = 19) were more likely to have a higher Grade Group and pathological stage at surgery, larger tumours, lymph node involvement and positive margins.

Conclusions

We demonstrate that one‐third of the ProtecT cohort consists of people with intermediate‐/high‐risk disease, and the outcomes data at an average of 10 years’ follow‐up are generalizable beyond men with low‐risk PCa.

BJUI Podcasts are available on iTunes: https://itunes.apple.com/gb/podcast/bju-international/id1309570262

April 2020 – about the cover

April’s article of the month is Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review by Franco, Turk, Jung, Xiao, Iakhno, Tirapegui, Garrote and Vietto. As some of these authors are based in Argentina we have chosen a scene from the capital city, Buenos Aires, for the issue cover.

La Boca is a barrio of Buenos Aires with an Italian feel as many of its settlers originated from Genoa. It is located at the mouth of the Matanza river, hence the name. It is a popular tourist destination due to the colourful houses and street tango but it is also home to the world-famous Boca Juniors football team.

© istock.com/Gim42

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