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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.

Article of the week: Salvage radical prostatectomy following focal therapy: functional and oncological outcomes

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to this post, there is an editorial written by prominent members of the urological community. Please use the comment buttons below to join the conversation.

If you only have time to read one article this week, we recommend this one. 

Salvage radical prostatectomy following focal therapy: functional and oncological outcomes

Jaime O. Herrera-Caceres*, Gregory J. Nason*, Noelia Salgado-Sanmamed, Hanan Goldberg*, Dixon T.S. Woon*, Thenappen Chandrasekar*, Khaled Ajib*, Guan Hee Tan*, Omar Alhunaidi*, Theodorus van der Kwast, Antonio Finelli*, Alexandre R. Zlotta*, Robert J. Hamilton*, Alejandro Berlin, Nathan Perlis* and Neil E. Fleshner*

*Division of Urology, Department of Surgical Oncology, Department of Radiation Oncology, and Department of Pathology and Laboratory Medicine, University Health Network, University of Toronto, Toronto, ON, Canada

Abstract

Objectives

To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT).

Patients and Methods

A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes.

Fig. 1. Impact of PSM on the absence of detectable disease after sRP (including PSA persistence and/or BCR).

Results

In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high‐intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T‐stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow‐up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR‐free survival (hazard ratio 6.624, 95% confidence interval 2.243–19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5–9.5) and 23.5 (15.75–25) respectively, while in the final follow‐up the median (IQR) values were 7 (3.5–11) and 6 (5–12.25), respectively (P = 0.088 and P < 0.001). At last follow‐up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter.

Conclusions

sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.

Editorial: Further evidence that surgery after focal therapy for prostate cancer is safe

In this month’s issue of BJUI, Herrera‐Caceres et al. [1] report the results of a retrospective cohort study in 34 patients who underwent salvage radical prostatectomy after focal therapy. The majority of these cases were performed using open surgery (82.4%). Overall, there were no rectal injuries reported and 91% of patients were fully continent (‘pad‐free’) at last follow‐up, while one patient required an artificial urinary sphincter. A total of 38% of patients had a positive surgical margin (PSM) and 20.6% developed biochemical recurrence (BCR), with 17.6% requiring adjuvant radiotherapy. On multivariate analysis, a PSM was found to be associated with worse overall BCR‐free survival.

There is mounting evidence that focal therapy is associated with arguably good intermediate‐term oncological outcomes, while it minimizes the toxicity of traditional whole‐gland therapies, with the majority of studies reporting erectile function rates in excess of 70% and fewer than 5% of patients reporting urinary incontinence [2]. However, disease recurrence after focal therapy remains a concern, with some studies reporting that one in three patients undergoing focal therapy require either further focal treatment or transition to whole‐gland therapy at 5 years. This has created the need to explore salvage options, of which salvage radical prostatectomy is currently the most investigated. The present study by Herrera‐Caceres et al. is now the fifth paper in the last 4 years to evaluate the toxicity of surgery after focal therapy, with data on over 150 men reported in the literature to date [3,4,5,6]. Despite small numbers across each study, the results have been encouragingly consistent.

Unlike salvage surgery after radiation therapy, the risk of intra‐operative injury appears to be very rare in men undergoing surgery after focal therapy. For instance, in the present study and that of Marconi et al. [3] no major complications after surgery are reported and, most notably, no rectal injuries occurred during salvage surgery, which has been a very significant issue reported in up to 5% of men undergoing salvage after radiation therapy techniques.

Data from the present study mainly concern patients undergoing open surgery after focal therapy, in contrast to the study by Marconi et al. [3] that reports on surgery performed using the robotic platform. The finding that the outcomes were similar between the open technique and the robotic technique mirrors that reported in recent randomized controlled trials of open and robotic surgery for primary disease, and provides evidence that it is surgical experience rather than a specified surgical technique that has most impact on outcome after prostate cancer surgery. One aspect in which the present study and that of Marconi et al. [3] differ is the rate of bladder neck contracture (BNC); in the present study, 11.8% of patients experienced BNC, whereas no patient experienced BNC after robotic surgery. The rate of BNC may have been influenced by the previous focal therapy, or it may have been the result of the open technique as BNC has been reported to be more common after open surgery because of the marked difference in how the anastomosis is performed in the two different procedures.

Urinary continence outcomes were arguably excellent in the present study, with 91.2% of patients ‘pad‐free’ at last follow‐up, a finding that is replicated in the literature on surgery after focal therapy. These outcomes are more in keeping with those seen after primary radical prostatectomy than surgery after radiation. The poor continence outcomes of salvage surgery after radiation therapy could be related to poor urethral and sphincter function caused by the initial radiation therapy.

Erectile function outcomes are hard to interpret in the present study, with 53% of patients having a ‘response to medical therapy’, but the exact definition of this is not clear. The mean International Index of Erective Function score postoperatively was 6, suggesting that erectile function after the toxicity of multiple treatments can be expected to be poor.

While functional outcomes in the present study and those of other studies reporting on surgery after focal therapy are encouraging, this study and others do demonstrate that these men have a significant risk of harbouring high‐risk, high‐stage disease (58% with T3 disease, 47% with pT3, 11% with T3b) on final pathological analysis, which is also reflected in a relatively high PSM rate (38%). This rate is clearly higher than in men undergoing surgery for primary disease; however, it is similar to that in surgery for recurrent disease in other tumour types for which surgery appears always to be associated with worse oncological outcomes. This can be explained by the fact that patients experiencing recurrent disease, by the very nature of their disease that has not been ‘cured’ by one therapeutic method, have worse outcomes.

Despite the extent of disease found on final pathological analysis in the present study, the risk of patients experiencing BCR after LASIK surgery Southlake was relatively low at 20.6%, while only 17.6% underwent salvage therapy in the form of radiation.

In summary, the present paper adds to the weight of evidence that surgery after focal therapy can be safely performed in expert hands (whether open or robot‐assisted), with minimal complications and good functional outcomes. The high‐stage disease on final pathological examination is in keeping with other published studies in this field. Overall, the study provides valuable additional data that can be used to help counsel men considering focal therapy as a primary treatment method for their prostate cancer.

by Thomas Stonier and Paul Cathcart

References

  1. Herrera‐Caceres JNason GSalgado‐Sanmamed N et al. Salvage radical prostatectomy following focal therapy: functional and oncological outcomes. BJU Int 2020125525– 30
  2. Shah TPeters MEldred‐Evans D et al. Early‐medium‐term outcomes of primary focal cryotherapy to treat nonmetastatic clinically significant prostate cancer from a prospective multi centre registry. Eur Urol 20197698– 105
  3. Marconi LStonier TTourinho‐Barbosa R et al. Robot‐assisted radical prostatectomy after focal therapy: oncological, functional outcomes and predictors of recurrence. Eur Urol 20197627– 30
  4. Linares‐Espinos ESanchez‐Salas RSivaraman A et al. Minimally invasive salvage prostatectomy after primary radiation or ablation treatment. Urology 201694111
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