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Editorial: HoLEP is the complete technique for treating BPH

Ten years of experience with holmium laser enucleation of the prostate (HoLEP) are documented by Romero‐Otero et al. [1] and offer valuable insight into the real‐world use of this technique. No information on the 10‐year durability is available, however, as only the 12‐month data are presented, but there is a wealth of other information concerning both peri‐operative outcomes and complications. A particular strength of this paper is that all‐comers were studied, including patients with catheters, those with prostates larger than 100 g and those taking anti‐coagulants, plus there is the addition of the cases the three surgeons performed during their ‘learning curve’, although these are not analysed separately.

The authors’ technique almost certainly evolved over the study period. Personally, I currently find a one‐ or two‐piece enucleation to be more efficient than the three‐lobe technique originally described [2]. Enucleation efficiency of 1–2 g/min, as was achieved in this series (73 g in 40 min), is a good benchmark for tissue removal for those new to the technique and is a good measure of surgical proficiency. Being less aggressive anteriorly seems to have an impact on continence. It is often tempting to completely enucleate circumferentially in one continuous plane which is sometimes well beyond the commissure anteriorly. A more moderate dissection in this area can reduce the transient incontinence sometimes seen [3]. The incontinence rates in the current series of 12.8% at 3 months and 2.3% at 12 months are probably representative [1]. An analysis of the factors predisposing to moderate‐to‐severe incontinence in the six patients in this series would have been useful, particularly regarding prostate size, presence of a catheter and age.

The main contribution of HoLEP to the urological armamentarium is its ability to safely treat large prostates endoscopically [4]. Although robot‐assisted techniques have also decreased the morbidity of open prostatectomy [5], the attraction of the obvious ‘natural orifice’ for access and the use of laser technology for the enucleation with HoLEP is probably the least morbid and most cost‐effective way to treat these patients. Tackling a prostate larger than 100 g involves applying the same principles as for smaller prostates, with a few provisos. Firstly, having a consistent strategy for these large prostates is important and can be reassuring when things become difficult. Secondly, it is even more important to maintain the correct plane religiously as it is easier to get lost in these glands. A good sense of direction is important! Thirdly, stay ahead of the bleeding rather than trying to catch up as it can further compound an already difficult situation. Patience is a virtue.

The learning curve of HoLEP has historically been regarded as a major barrier to the uptake of the technique [6]. This has, of course, been exaggerated by proponents of other techniques, but it is important to emphasize that during this learning phase the excellent outcomes are maintained and that conversion to TURP, if necessary (3.4% in this series), can be safely done, as these authors’ have demonstrated. The length of the learning curve has been variously described as being between 20 and 80 cases and is almost entirely due to the way training is done. A modular mentored approach appears to be the best method and could equally be applied to endoscopic enucleation using any of the other energy sources that have been described [7].

HoLEP and all its progeny are here to stay, but which of these enucleation energy sources will gain ascendancy remains to be seen. Sadly, this will likely be more to do with the depth of the corporate pockets and their commitment to the cause rather than proper scientific appraisal [8].

by Peter Gilling

References

  1. Romero‐Otero J, Garcia‐Gomez B, Garcia‐Gonzalez L et al. Critical analysis of a multicentric experience with holmium laser enucleation of the prostate for benign prostatic hyperplasia: outcomes and complications of 10 years of routine clinical practice. BJU Int 2020; 126: 177-182
  2. Gilling PJ, Kennett K, Das AK, Thompson D, Fraundorfer MR. Holmium laser enucleation of the prostate (HoLEP) combined with transurethral tissue morcellation: an update on the early clinical experience. J Endourol 1998; 12: 457– 9
  3. Tunc L, Yalcin S, Kaya E et al. The “Omega Sign”: a novel HoLEP technique that improves continence outcomes after enucleation. World J Urol 2020 https://doi.org/10.1007/s00345-020-03152-9
  4. Gilling PJ, Kennett KM, Fraundorfer MR. Holmium laser enucleation of the prostate for glands larger than 100 g: an endourologic alternative to open prostatectomy. J Endourol 2000; 14: 529– 31
  5. Mourmouris P, Keskin SM, Skolarikos A et al. A prospective comparative analysis of robot‐assisted vs open simple prostatectomy for benign prostatic hyperplasia. BJU Int 2019; 123: 313– 7
  6. Placer J, Gelabert‐Mas A, Vallmanya F et al. Holmium laser enucleation of prostate: outcome and complications of self‐taught learning curve. Urology 2009; 73: 1042– 8
  7. Kuronen‐Stewart C, Ahmed K, Aydin A et al. Holmium Laser Enucleation of the prostate: simulation based training curriculum and validation. Urology 2015; 86: 639– 46.
  8. Herrmann TR. Enucleation is enucleation is enucleation is enucleation. World J Urol 2016; 34: 1353– 5

Editorial: How can we motivate patients with bladder cancer to help themselves?

Wash your hands. Cover your mouth when you cough. Do not spread germs. We have all heard these hygiene mantras growing up, but we must admit that compliance has not always been perfect. With the coronavirus disease 2019 (COVID‐19) pandemic raising mounting alarm, fear has persuaded unprecedented adherence to hygiene principles globally, as we try to stop the spread of this novel virus.

What motivates a change in behaviour? What motivates someone to stop a bad habit and adopt a good one? Can clinicians aid in this motivation?

Chung et al. [1] performed a cross‐sectional study evaluating health behaviours including physical activity, diet, body mass index, alcohol consumption, and smoking status, as well as health‐related quality of life (HRQoL) in patients with bladder cancer at different treatment stages. In their study sample, most of the patients with bladder cancer were overweight or obese, did not adhere to healthy diet recommendations, were unwilling to change their eating habits, and did not meet guidelines for weekly physical activity. However, patients who had adopted healthy behaviours reported a better HRQoL and more healthy behaviours correlated with a better HRQoL. No difference was found when comparing the health behaviours of patients with non‐muscle vs muscle‐invasive bladder cancer (MIBC) or comparing patients at different stages of treatment. This implies that patients’ health behaviour does not change despite bladder cancer diagnosis and treatment; however, pre‐diagnosis data were unavailable for comparison. Interestingly, the large majority of the patients with bladder cancer were non‐smokers (81%), despite most (71%) reporting a prior history of smoking. What led to a change in smoking status when it appears that no other health behaviour changed with diagnosis and treatment of bladder cancer?

Gallus et al. [2] surveyed 3075 ex‐smokers in Italy to answer the question: why do smokers quit? The most frequently reported reason for smoking cessation (43.2%) was a current health problem. Smoking has been linked to the development of numerous medical conditions and is a well‐established risk factor for bladder cancer. Thus, a new diagnosis of bladder cancer undoubtedly serves as a strong motivator for smoking cessation. The benefits of a healthy diet and regular physical activity on one’s health are less defined. Furthermore, the definitions of a ‘healthy’ diet and ‘regular’ physical activity are variable, making counselling about these behaviours confusing and difficult. Dolor et al. [3] found that physicians feel inadequately trained to provide diet counselling to patients as compared to smoking cessation counselling. Additionally, physicians agreed that counselling regarding weight loss, diet, and physical activity requires too much time compared to smoking cessation counselling. These discrepancies may help explain why physicians were more likely to discuss smoking cessation with patients compared to weight loss, diet, and physical activity in a study by Nawaz et al. [4].

At our own institution, we have found that HRQoL significantly declines in patients with bladder cancer after diagnosis relative to controls, with more pronounced decreases seen in patients with MIBC [5]. Patients with bladder cancer are a vulnerable population who face many medical and personal challenges. As clinicians, we should equip these patients with the proper tools to succeed during bladder cancer treatment, including counselling regarding healthy behaviours. Inviting the help of specialists, such as nutritionists and physical therapists, to discuss the importance of diet and exercise early during treatment may be advantageous for patients and more likely to motivate patients to adopt these healthy behaviours. Furthermore, given the paucity of data linking the health behaviours of patients with bladder cancer to HRQoL, studies such as this one [1] could provide much‐needed evidence to persuade patients regarding the positive impact that healthy behaviour can have on their HRQoL. If we can successfully motivate patients with bladder cancer to adopt healthy behaviours, then their HRQoL will likely improve.

by Hannah McCloskey, Judy Hamad, Angela B. Smith

References

  1. Chung J, Kulkarni GS, Bender J et al. Modifiable lifestyle behaviours impact the health‐related quality of life of bladder cancer survivors. BJU Int 2020; 125: 836– 42
  2. Gallus S, Muttarak R, Franchi M et al. Why do smokers quit? Eur J Cancer Prev 2013; 22: 96– 101
  3. Dolor RJ, Østbye T, Lyna P et al. What are physicians’ and patients’ beliefs about diet, weight, exercise, and smoking cessation counseling? Prev Med 2010; 51: 440– 2
  4. Nawaz H, Adams ML, Katz DL. Physician–patient interactions regarding diet, exercise, and smoking. Prev Med 2000; 31: 652– 7
  5. Smith AB, Jaeger B, Pinheiro LC et al. Impact of bladder cancer on health‐related quality of life. BJU Int 2018; 121: 549– 57

Editorial: Low-dose-rate brachytherapy for prostate cancer stands the test of time – the Swiss experience

The clinical results from 12 Swiss centres reaffirm the benefits of Low Dose Rate Brachytherapy (LDR-BT) for the treatment of localised prostate cancer [1]. The authors are to be commended for collating and analysing prospective, countrywide, long-term data. This is an excellent example of Good Clinical Practice for the urology community, patients, commissioning groups and for governance purposes. Prostate brachytherapy offers suitable men with prostate cancer a high chance of long-term cure but with a low risk of urinary incontinence and most retaining erectile dysfunction [2].

Two thirds of the patients reported in the Swiss series had low-risk cancer who would now more commonly be offered active surveillance as an initial treatment option. However our own and other large mature series have shown similar treatment efficacy of LDR-BT, either as monotherapy as in the Swiss study, or as a boost to external-beam radiotherapy, for the treatment of patients with intermediate and high risk of disease relapse [3, 4]. Indeed the ASCENDE-RT trial recently showed that men with unfavourable intermediate or high-risk prostate cancer randomised to an LDR-BT boost arm, relative to a dose-escalated external-beam radiotherapy boost, were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years. A slight increase in urinary toxicity was observed which may have been an issue related to implant technique [5].

The authors show LDR-BT affords excellent disease control that associates with post-implant dosimetry in keeping with current treatment guidelines. They also report an association between biochemical control and seed loss. It therefore becomes unclear the extent to which implant quality or implant technique, i.e. the use of loose or stranded seeds, influenced the oncological outcome, as it would appear that more than one brachytherapy technique has been used.

In this series no prostate cancer-related deaths were reported. However the median follow-up length of 37 months is relatively short. Examples from more mature series show longer follow-up is needed to begin to document the low rates of prostate cancer-related deaths following LDR-BT. Lazarev et al [6] in a similar risk group distribution to the Swiss population, reported 97% prostate cancer-specific survival at 17-years with all deaths occurring more than 10 years after treatment. Morris et al [4] reported 99.1% cause-specific survival at 10 years with death events 9 years after treatment in low and intermediate-risk disease. Our own series showed 98% prostate-cancer-specific survival at 7 and 9 years post-implantation in high-risk (as defined by NICE) patients treated with monotherapy [3].

Treatment-related toxicity assessments in the Swiss series showed that baseline values are crucial to understand the impact of treatment on patient-reported outcomes. Higher post-implant scores were consistently observed in those patients with higher baseline scores. The patient-reported outcomes were similar to those from our series where sexual potency was preserved in 70-80% of men who were ≤60 years old at time of implant [7].

Salvage therapies are seldom given after LDR-BT as the local failure rate is low and the surgery complex. It was undertaken in only two patients in the Swiss series. In the era of mp-MRI and PSMA PET/CT scans and targeted biopsies, tumour recurrence can be better assessed.  Salvage surgery has been offered to approximately 0.5% (27/4200) of our patients, by either robotic-assisted radical prostatectomy or seminal vesiculectomy if the recurrence is localised to the seminal vesicle alone.

This nation-wide report from the 12 Swiss centres is a welcome addition to the extensive body of evidence that attests to the excellent results and generalisability of prostate LDR-BT. The treatment is efficacious and convenient for patients with a low toxicity profile. It is a cost effective option that should be offered to all suitable patients with localised prostate cancer.

by Stephen Langley

References

1. Viktorin-Baier P, Putora PM, Schmid HP, et al. Long-term oncological and functional follow-up in low-dose-rate brachytherapy for prostate cancer: results from the prospective nationwide Swiss registry. BJU Int 2020: 125(6).

2. Punnen S, Cowan JE, Chan JM, Carroll PR, Cooperberg MR. Long-term health-related quality of life after primary treatment for localized prostate cancer: results from the CaPSURE registry. European urology 2015; 68: 600-608.

3. Laing R, Uribe J, Uribe-Lewis S, et al. Low-dose-rate brachytherapy for the treatment of localised prostate cancer in men with a high risk of disease relapse. BJU Int 2018; 122: 610-617.

4. Morris WJ, Keyes M, Spadinger I, et al. Population-based 10-year oncologic outcomes after low-dose-rate brachytherapy for low-risk and intermediate-risk prostate cancer. Cancer 2013; 119: 1537-1546.

5. Morris WJ, Tyldesley S, Rodda S, et al. Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer. Int J Rad Onc Bio Phys 2017; 98: 275-285.

6. Lazarev S, Thompson MR, Stone NN, Stock RG. Low-dose-rate brachytherapy for prostate cancer: outcomes at >10 years of follow-up. BJU Int 2018; 121: 781-790.

7. Langley SEM, Soares R, Uribe J, et al. Long-term oncological outcomes and toxicity in 597 men aged ≤60 years at time of low-dose-rate brachytherapy for localised prostate cancer. BJU Int 2018; 121: 38-45.

Editorial: Prostate cancer and kidney transplantation – exclusion or co‐existence?

Untreated prostate cancer is generally a contraindication to kidney transplantation. At our institution in Boston, we are often referred individuals with low‐volume low‐risk prostate cancer for treatment. For a cancer that would otherwise be managed with active surveillance, these kidney transplantation candidates will often be forced into some form of definitive therapy, generally radical prostatectomy, a procedure with a well‐known long‐term side‐effect profile, and then have to wait for a period of time, generally 2 years, before being considered for transplantation. The basis for this approach stems from the theoretical higher risk of disease progression and ultimately mortality on immunosuppression. In this issue of the BJU International, Bratt et al. [1] challenge these assumptions and report on the outcomes of kidney transplant recipients diagnosed with prostate cancer. First, they found no difference in prostate cancer incidence, suggesting that transplant recipients, despite being immunosuppressed, are not at higher risk of prostate cancer. Second, they found that the prostate cancer characteristics at diagnosis, overall and prostate cancer‐specific survival of kidney transplant recipients do not differ significantly from non‐transplant patients. Furthermore, the probability of developing advanced prostate cancer over time was not higher among transplant recipients on immunosuppression. Taken together, these findings show that transplant patients are not at a higher risk of poor prostate cancer outcomes.

Hypothesising that many of the transplant recipients in this study already had prostate cancer when they underwent transplantation (based on assumptions about cancer screening practices in Sweden and the time periods included), the authors aim to refute current transplantation guidelines contraindicating solid organ transplantation in those with a history of prostate cancer and requiring a minimum recurrence‐free period before placing these patients on the organ waiting list [23]. The findings of Bratt et al. [1] corroborate previous case series including the largest study of cancer incidence among transplant recipients and a meta‐analysis of six studies. Given the available data, is it still justifiable to deny patients with low‐risk prostate cancer life‐saving kidney transplantation? If the answer is ‘no’, what would be fair cutoffs in Gleason score, number of positive biopsy cores, PSA level, time from diagnosis, etc.? While this study does not definitely answer the question, it would seem reasonable that candidates for active surveillance, especially those with very low‐risk prostate cancer, should be eligible for kidney transplantation without prior definitive therapy. Denying immediate placement on the waiting list represents not only a significant reduction of quality of life, but also leads to reduced survival due to longer dialysis time.

Another concern often heard from those in favour of definitive therapy before transplantation is the added risks of prostatectomy in immunosuppressed individuals; this is understandable given that the incidence of definitive therapy on active surveillance is ~50% at 10 years after diagnosis [4]. However, the available data suggest that prostatectomy after transplantation is safe. For example, in a recent systematic review, only one of 35 patients had a Clavien ≥ 3 complication and graft function was maintained in all patients [5]

To summarise, this study [1], and others before that, suggests that immunosuppression after kidney transplantation is unlikely to adversely affect prostate cancer initiation or progression. Men with low‐risk prostate cancer should be considered for transplantation without first undergoing definitive therapy. There is evidence around the world, and at our institution, that transplant specialists are finally starting to accept this pathway. This study will further reinforce this concept.

by Lorine Haeuser, David‐Dan Nguyen Quoc‐Dien Trinh

References

  1. Bratt O, Drevin L, Prütz K‐G, Carlsson S, Wennberg L, Stattin P. Prostate cancer in kidney transplant recipients – a nationwide register study. BJU Int 2020; 125: 679– 85
  2. Murray KF, Carithers RL. AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatology 2005; 41: 1407– 32
  3. Oechslin E, Kiowski W, Schneider J, Follath F, Turina M, Gallino A. Pretransplant malignancy in candidates and posttransplant malignancy in recipients of cardiac transplantation. Ann Oncol 1996; 7: 1059– 63
  4. Tosoian JJ, Mamawala M, Epstein JI et al. Intermediate and longer‐term outcomes from a prospective active‐surveillance program for favorable‐risk prostate cancer. J Clin Oncol 2015; 33: 3379– 85
  5. Zeng J, Christiansen A, Pooli A, Qiu F, LaGrange CA. Safety and clinical outcomes of robot‐assisted radical prostatectomy in kidney transplant patients: a systematic review. J Endourol 2018; 32: 935– 43

Editorial: The provision of comfort – addressing barriers to sleep in prostate cancer

“In whatever disease sleep is laborious, it is a deadly symptom,” is a famed aphorism by Hippocrates, because he deeply understood the role of sleep in the process of healing. One of the main goals of any comprehensive cancer management plan should be the provision of comfort. In academic literature, discussions of advances in prostate cancer treatment are often limited to novel therapeutics, such as immunotherapy. What gets often ignored in these discussions is the patient’s perspective—especially that of sleep disturbances. This is why an intriguing qualitative analysis in this BJUI issue by Robbins et al is a refreshing read [1]. The authors examined discussions on an online health community to elucidate the barriers to sleep among prostate cancer patients and caregivers.

Parsing through thousands of anonymized public comments, the authors report several interesting findings: one, majority of comments related to sleep (86%) are posted by patients—signifying high interest in this aspect of management; second, a plurality of comments discuss sleep medications (22%), with comments about advanced disease discussing these medications three times more than those discussing localized disease; third, associated side effects of fatigue and pain were largely observed in advanced disease comments, also we have noticed that many people is using this website https://observer.com/2020/05/best-cbd-hemp-flower/ to buy CBD and reduce the pain cause by the disease. Interestingly, the authors also used Linguistic Inquiry Word Count (LIWC) software—a reasonable tool to assess emotional states—and reported that advanced disease comments were significantly more negative in perspective than localized disease comments. This analysis is an especially useful contribution—and should enable contemporary Prostate Cancer Survivorship Care Guidelines to expand on the impact of sleep disturbances [1].

These findings have considerable implications. To start with, these findings need to be contextualized within the larger body of evidence we have on impact of sleep disturbances on prostate cancer. In a recent study, Markt et al prospectively followed 32,141 men (with 4261 prostate cancer cases) using the Health Professionals Follow-Up Study (HPFS), and found no association between self-reported duration of sleep and prostate cancer outcomes [2]. However, the authors of the HPFS study did emphasize that sleep disruptions were associated with increased risk of developing lethal or aggressive prostate cancer. The finding by Robbins et al that a significant proportion of patients are discussing these issues through online communities suggests that the prevalence of sleep disturbance—and its impact on quality of life—among prostate cancer patients is poorly understood and inadequately measured.

Representative quotes highlighted by Robbins et al also reveal that prostate cancer patients often suffer from severe insomnia, indicating lack of sleep-related patient education initiatives. Additionally, quotes by caregivers also underscore that there is a general lack of information on how to address sleep disruptions for patients they attend to. This is a missed opportunity, as evidence suggests that nutritional therapy (soy supplementation, for example) and combination of resistance training with aerobic exercise may improve cancer related fatigue and quality of life among prostate cancer patients [3], although less is known about effective interventions that would improve sleep. Furthermore, disturbances in sleep have expensive implications for health care spending and workplace absenteeism—with prostate cancer survivorship phase accounting for 50% of total cancer care related costs [4]. Studies that have investigated this relationship report that sleep disturbances significantly increase the utilization of health care and workplace absenteeism, with the impact constituting 2% and 8%, respectively [4]. Given the exponential rise in overall health care spending in the United States, addressing costs stemming from preventable adverse events is urgent—this present study demonstrates that more creative interventions are wanting.  

Beyond economic and survivorship care concerns, this qualitative study paints a grim picture of the conversations happening in these online patient communities, with comments revealing a negative emotional state for many. While sleep disturbances are an important contributor for this development, lack of patient education can also engender greater confusion and distress. Findings from this study should spur greater interest and support for devising and implementing patient-centered initiatives that improve sleep quality. This is required not only because these will likely improve the quality of life for prostate cancer patients, but also because we have a moral responsibility to provide comfort for these patients.

by Junaid Nabi

References

1.         Robbins R, Girardin JL, Chanko N, Combs, P, Byrne N, Loeb S Using data from an online health community to examine the impact of prostate cancer on sleep. BJU Int. 2020; 125(5).

2.         Markt SC, Flynn-Evans EE, Valdimarsdottir UA, Sigurdardottir LG, Tamimi RM, Batista JL, et al. Sleep Duration and Disruption and Prostate Cancer Risk: a 23-Year Prospective Study. Cancer Epidemiol Biomarkers Prev. 2016;25(2):302-8.

3.         Baguley BJ, Bolam KA, Wright ORL, Skinner TL. The Effect of Nutrition Therapy and Exercise on Cancer-Related Fatigue and Quality of Life in Men with Prostate Cancer: A Systematic Review. Nutrients. 2017;9(9):1003.

4.         Gonzalez BD, Grandner MA, Caminiti CB, Hui S-KA. Cancer survivors in the workplace: sleep disturbance mediates the impact of cancer on healthcare expenditures and work absenteeism. Support Care Cancer. 2018;26(12):4049-55.

Editorial: Fake news about benign prostatic hyperplasia on YouTube

YouTube is a widely used video‐sharing and social networking platform. It contains a large volume of content about medical topics, including urological conditions. In this issue of BJUI, Betschart et al. [1] examined the quality of 159 YouTube videos about surgical treatment of BPH with ≥500 views. The median overall quality of videos was poor (2 out of 5 possible points) based on validated criteria for the assessment of consumer health information. Nearly 87% of videos contained some misinformation and 84% had commercial bias.

We previously reported similar findings in the first 150 videos in a YouTube search for prostate cancer [2]. The median overall quality of videos was moderate (3 out of 5 points), and 77% contained biased and/or misinformative content in the video or comments beneath it. Furthermore, videos with lower expert‐rated quality had higher user engagement.

In the study by Betschart et al. [1], most of the YouTube videos about BPH had very good production quality, and 69% were posted by healthcare providers (e.g., doctor, clinic, hospital or university). These attributes might lead health consumers to have more trust in the information that is provided. In fact, they found that two‐thirds of videos with the most views in each topic had a quality score below the median score for videos about that topic.

Unfortunately, these issues are pervasive across many health domains. A recent review article reported on the prevalence of commercial bias and misinformation in social media posts about a variety of urology topics, including female pelvic medicine, endourology, sexual medicine, and infertility [3].

What can be done to combat the large quantity of misinformative urological information circulating online? For BPH on YouTube alone, Betschart et al. [1] reported that there were >12 000 videos as of May 2019. It is not practical for medical experts to manually vet the vast and continually changing repository of online medical information.

One future possibility is the development of computational tools to help evaluate the quality of information. For example, using an annotated dataset of 250 YouTube videos about prostate cancer, we created an automatic classification model for the identification of misinformation with an accuracy of 74% [4]. Further study is warranted to develop and test the use of machine learning to help filter the quality of online content.

As healthcare providers, what can we do to address these problems in the near‐term? We previously reported that USA adults who perceive worse patient‐physician communications are significantly more likely to watch health videos on YouTube [5]. This highlights the importance of shared decision‐making and proactively directing our patients to trusted sources of information. A curated list of reputable sources of online urological health information is presented in a recent review [6]. In addition, healthcare providers should be encouraged to actively participate in social media to flag any content that is inaccurate or dangerous and to help provide accurate information to the public. The BJUI, European Association of Urology, and AUA have all published guidance regarding best practices for social media engagement, which should be incorporated into urological education in the future [7].

In conclusion, social networks have a huge global audience and offer great potential to benefit the care of BPH and other urological conditions. However, to meet this potential and offset the risks will require significant ongoing efforts from the urological community.

by Stacy Loeb

References

  1. Betschart P, Pratsinis M, Müllhaupt G et al. Information on surgical treatment of benign prostatic hyperplasia on YouTube is highly biased and misleading. BJU Int 2020; 125: 595-601
  2. Loeb S, Sengupta S, Butaney M et al. Dissemination of misinformative and biased information about prostate cancer on YouTube. Eur Urol 2019; 75: 564– 7
  3. Loeb S, Taylor J, Borin JF et al. Fake News: Spread of misinformation about urological conditions on social media. Eur Urol Focus 2019 [Epub ahead of print].
  4. Hou R, Perez‐Rosas V, Loeb S, Mihalcea R. Towards Automatic Detection of Misinformation in Online Medical Videos. International Conference on Multimodal Interaction. Suzhou, Jiangsu, China: ACM, 2019. Available at: https://arxiv.org/abs/1909.01543. Accessed January 2020
  5. Langford A, Loeb S. Perceived patient‐provider communication quality and sociodemographic factors associated with watching health‐related videos on YouTube: a cross‐sectional analysis. J Med Internet Res 2019; 21: e13512. 
  6. Langford AT, Roberts T, Gupta J, Orellana KT, Loeb S. Impact of the internet on patient‐physician communication. Eur Urol Focus 2019: 31582312 [Epub ahead of print].
  7. Taylor J, Loeb S. Guideline of guidelines: social media in urology. BJU Int 2020; 125: 379-382

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
  5. Nunes‐Silva IBarret ESrougi V et al. Effect of prior focal therapy on perioperative, oncologic and functional outcomes of salvage robotic assisted radical prostatectomy. J Urol 20171981069– 76
  6. Thompson JSridhar ATan W et al. Pathological findings and magnetic resonance imaging concordance at salvage radical prostatectomy for local recurrence following partial ablation using high intensity focused ultrasound. J Urol 20192011134– 43

 

Editorial: Estimating the threat posed by prostate cancer

What is the threat posed by your disease? This is how I begin all my conversations with men who have newly diagnosed prostate cancer. For men with obvious metastatic disease, the conversation is relatively simple. They have a systemic disease that requires systemic therapy with anti‐androgen medications. However, for men with localised prostate cancer the conversation is more difficult, as it is unclear when the disease will become clinically apparent. The report by Bryant et al. [1,2] in this issue of the BJUI summarising the Prostate Testing for Cancer and Treatment (ProtecT) trial findings has provided us with critical data concerning the natural history of screen‐detected prostate cancer and the relative impact of treatment.

The ProtecT trial data are unique, in that the study is embedded within a screening trial [2]. The patients recruited to the study reflect outcomes of men with cancer identified by PSA testing. The study population differs from men enrolled in the Scandinavian Prostate Cancer Group Study number 4 (SPCG‐4), who were primarily diagnosed clinically and therefore do not have the lead time associated with screening [3]. The study cohort also differs from the men enrolled in the Prostate Intervention Versus Observation Trial (PIVOT), who were generally older and therefore more often succumbed to competing medical problems during follow‐up [4]. The former group is likely to have a higher incidence of clinically significant disease; the latter group is likely to have a lower disease‐specific mortality.

While the ProtecT trial data offer a reasonable approximation of clinical practice, the ProtecT patient cohort differs from contemporary North American patients who likely have had several PSA tests prior to the one that prompted a prostate biopsy, and from contemporary UK patients who now undergo biopsy as a result of a lesion seen on MRI. The former group is likely to have a higher incidence of low‐grade disease; the latter group is more likely to have a higher incidence of high‐grade disease. Fortunately, these selection biases do not detract significantly from the fundamental messages of the ProtecT trial.

So how have Bryant et al. [1] helped us? A review of Table 1 in the paper, confirms that the Gleason Grade Group is the most powerful predictor of disease progression and long‐term survival for men with screen‐detected disease. PSA testing preferentially identifies men with low‐grade disease, primarily because low‐grade disease is much more common than high‐grade disease. Only 6% of the ProtecT cohort had Gleason Grade Group ≥3 disease, but these men accounted for 37% of the men who progressed. In comparison, 92% of the cohort had Gleason Grade Group 1 disease and only 8% of these men showed signs of progression. Among those men who underwent a radical prostatectomy, five of the seven men who developed metastases or died from their disease had Gleason Grade Group ≥3. Clinicians can now confidently counsel men considering active surveillance regarding the 10‐year estimates of disease progression based upon the biopsy Gleason Grade Group alone.

But Bryant’s team provided additional important information. They have shown that clinical stage and preoperative PSA levels also contribute important prognostic information and when men are classified by Risk Group, men with intermediate‐risk disease have over four‐times the probability of progressing within 10 years of diagnosis when compared to men in the low‐risk group. This is very relevant to men in their 50s and 60s contemplating active surveillance and should inject a note of caution for men in their 70s.

Bryant et al. [1] also showed us that other factors were less valuable in predicting long‐term outcomes. Patient age, the number of cores positive, the presence of perineural invasion, provided some evidence of increased risk, but were much less persuasive in helping men decide upon an appropriate treatment pathway.

The authors close their manuscript with the statement that baseline clinical and pathological features associated with men with newly diagnosed prostate cancer are not strong enough to reliably predict individual progression. While this may be true, I do not think they give sufficient credit to their accomplishments. Their data are the most relevant outcomes data for men with screen‐detected prostate cancer, providing them with accurate estimates of the probability of disease progression, or lack thereof, over a 10‐year horizon. The infrequent disease progression among men with Gleason Grade Group 1 was a surprise finding from the ProtecT study. Since then, our protocols and tools for conducting active surveillance have improved significantly. The 15‐year data are likely to be available in another 2–3 years; hopefully, they will remain as encouraging.

by Peter Albertsen

References

  1. Bryant R, Oxley J, Young G et al. The ProtecT trial: analysis of the patient cohort, baseline risk stratification and disease progression. BJU Int 2020; 125: 505– 14
  2. Hamdy FC, Donovan JL, Lane JA et al. 10‐year outcomes after monitoring, surgery or radiotherapy for localized prostate cancer. N Eng J Med 2016; 375: 1415– 24
  3. Bill‐Axelson A, Holmberg L, Garmo H et al. Radical prostatectomy or watchful waiting in prostate cancer – 29 year follow up. N Eng J Med 2018; 379: 2319– 29
  4. Wilt TJ, Brawer MK, Jones KM et al. Radical prostatectomy versus observation for localized prostate cancer. N Eng J Med 2012; 367: 203– 13

Editorial: Chronic Prostatitis/Chronic Pelvic Pain Syndrome: It is time to change our management and research strategy

A urologist who manages patients with prostatitis (or for that matter, a patient suffering from the condition) would read the latest comprehensive review on pharmacologic interventions for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with despair.  In the Cochrane Systemic review examining the available clinical evidence for the efficacy of pharmacological interventions for treating CP/CPPS, Franco et al [1] clearly show that low to very low quality evidence suggests that some treatments may confer at best, only a small and perhaps clinically insignificant benefit for patients.  Are we doing something wrong?

To start with, we do not need to despair.  We are now managing men with CP/CPPS much better, achieving clinically significant improvement in over 80% of patients [2,3].  This real world management success story, which continues to evolve, clearly shows much greater benefit than that suggested by all the clinical trials assessed in this review.  Our similar independent patient data meta-analysis and comprehensive review of CP/CPPS management strategies [4] described very similar findings as that by Franco et al [1].  What intrigued us was the difference or the lack of correlation between overall symptom improvement (based on mean symptom score changes from baseline in the treated cohort of subjects compared to the placebo treated subjects) and the responder analyses which clearly showed some subjects had very significant responses despite the overall dismal mean symptom score differences in the entire population evaluated.  We saw this consistently in our clinical trials and we see this in our day-to-day practice; some patients do well with an intervention and others fail miserably.  Some of the problem lies in what we are measuring as outcomes in clinical treatment trials.  The NIH Chronic Prostatitis Symptom Index (CPSI) is a composite score evaluating many different parameters (eg location, frequency and severity) and domains (pain, urinary and impact/quality of life) and while very useful to look at the clinical picture in each individual patient, should not be used as a primary endpoint or outcome of a clinical trial.  The CPSI Pain domain is better but it still examines too many parameters (location, frequency and severity of pain).  The NIH CPSI question #4, which is an NRS measurement of only pain severity, is in fact a validated outcome that can be compared between groups.  However, CP/CPPS is much more complicated than just pain and that is why a patient driven subjective global assessment may be a more appropriate outcome, certainly in clinical practice.  We need more CP/CPPS patient directed specific measurement tools to really assess the benefits of our treatments in individual patients, or at least in intervention-specific domains.

We now know the reason for this discrepancy between the overall population symptom score difference and the individual responder rate.  We have learned that we cannot treat or manage CP/CPPS patients as a homogeneous group and hope that one treatment will benefit them all.  We now know that the men suffering from CP/CPPS are a clinically heterogeneous group with different mechanisms of disease, spectrum of clinical symptoms and physical examination parameters.  We have learned to identify the various clinical phenotypes based on a UPOINT categorization [5].   By assessing the contribution of urinary, psychosocial, organ specificity (eg prostate, penis, testes, etc), infection, neurogenic/neuropathic and tenderness of skeletal muscles (eg pelvic floor) contributions in each individual, we identify targets of intervention.  These individualized multimodal treatment plans that we develop for each patient has led to clinical success in managing the majority of CP/CPPS patients [3,6]. In future we hope to understand the mechanisms for these phenotypes and develop biomarkers to better differentiate them.

What have I learned from Franco et al‘s comprehensive review of CP/CPPS treatments [1]? We must stop designing and performing these monotherapy treatment trials in which we enroll all subjects with a diagnosis of CP/CPPS. These type of clinical studies have been mainly driven by government regulatory rules in attempts to have drugs approved for CP/CPPS treatment. We should consider trial design where the patient eligibility criteria is definitive and clear enough so that we enroll only patients with a phenotype and/or mechanism that the specific therapy is directed towards – domain-specific trial design. Better yet, we must discover CP/CPPS biomarkers (urine, serum and/or prostate fluid) that will allow us to differentiate mechanisms and allow more effective directed therapy.  We must consider more complicated and novel trial designs in which multimodal therapies can be assessed in different populations.  I would propose a Multi-Intervention for Pelvic Pain Study (MIPPS) be designed and considered for CP/CPPS in which multimodal treatments designed for specific phenotype domains or disease mechanisms are evaluated in specific individuals.  It is anticipated that such a real world experience study (designed to mimic real life clinical practice) would result in much better outcomes for patients. Going forward it is time to not only change our management approach, but also our research strategies.

by J. Curtis Nickel

References

1. Franco JVA, Turk T, Jung JH, Xiao Y, Iakhno S, Tirapegui F, et al. Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review. BJU Int. 2020; 125.

2. Shoskes DA, Nickel JC, Kattan M. Phenotypically Directed Multimodal Therapy for Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Prospective Study Using UPOINT. Urol. 2010;75:1249-1253.

3. Doiron RC, Nickel JC. Management of chronic prostatitis/chronic pelvic pain syndrome. Can Urol Assoc J. 2018;12(6 Suppl 3):S161-S163

4. Anothaisintawee T, Attia J, Nickel JC, Thammakraisorn S, Numthavaj P, McEvoy M, Thakkinstian A. The Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A systematic review and network meta-analysis. JAMA. 2011;305:78-86.

5. Shoskes DA, Nickel JC, Rackley RR, Pontari MA. Clinical Phenotyping in Chronic Prostatitis/Chronic Pelvic Pain Syndrome and Interstitial Cystitis: A Management Strategy for Urologic Chronic Pelvic Pain Syndromes.  Prostate Cancer Prostatic Dis. 2009;12:177-83.

6.  Shoskes D, DeWitt-Foy ME, Nickel JC. Management of Chronic Prostatitis/Chronic Pelvic Pain Syndrome.  European Urology Focus 2019;5: 2-4.

Editorial: Magnetic resonance imaging as a personalised tool to safely avoid prostate biopsy

Identifying men at risk of developing clinically significant prostate cancer (csPCa) who are either biopsy naïve or have undergone a prior negative systematic biopsy remains a dilemma for urologists seeking to utilise clinical resources in a cost‐conscious and safe manner. Clinical and demographic factors including DRE findings, serum PSA concentrations, race/ethnicity, and family history, guide shared decision‐making to pursue an initial or repeat prostate biopsy. Despite thoughtful risk assessments, the screening tools implemented often lead to biopsies where a majority demonstrates benign pathology findings or indolent forms of PCa that would not mandate immediate, definitive intervention. Hence, various risk models (RMs) have been proposed to stratify men who have a greater likelihood of harbouring csPCa, and several now incorporate findings from multiparametric MRI (mpMRI) by assessing suspicious lesion characteristics into their algorithms. While promising, most of these models were generated using single‐institution retrospective data and lack the external validation that could make them more generalisable and widely adopted in clinical practice.

In the present issue, Püllen et al. [1] evaluate three RMs that incorporate mpMRI findings using a cohort of 307 men who were biopsy naïve or had previously undergone a negative prostate biopsy. Risk of csPCa according to the MRI‐European Randomized Prostate Screening for Prostate Cancer Risk Calculators 3 and 4 (MRI‐ERSPC‐3/4) [2], Radtke’s RM (ModRAD) [3], and Distler’s RM (ModDis) [4] were compared to final pathology after TRUS‐guided perineal prostate biopsy with MRI‐fusion targeted sampling, as indicated using a Prostate Imaging‐Reporting and Data System version 2 (PI‐RADSv2) score ≥3 as the threshold.

The cohort had a median age of 67 years, median PSA concentration of 8.8 ng/mL, and there were 453 PI‐RADSv2 ≥3 lesions, which is consistent with a typical at‐risk screening population. Amongst these men, 134 (40%) harboured csPCa defined as a Gleason Grade Group ≥2. All three RMs performed similarly on receiver operating curve analyses with area under the curve for prediction nearing 0.85 for finding csPCa in both biopsy naïve and prior negative‐biopsy patients. Using a 15% risk threshold, the adapted MRI‐ERSPC‐3/4 RM would have safely avoided 30% of biopsies with 6% of csPCa diagnoses being missed, whereas the ModRad and ModDis RMs would have only avoided 17% and 6% of unnecessary biopsies, respectively, albeit with far fewer occult cases of csPCa.

The integration of mpMRI in the pre‐biopsy setting is being more widely adopted into the clinical landscape, with emerging support largely due to its value in detecting csPCa, but also the recognised high negative predictive value potentiating the safe avoidance or deferral of prostate biopsy [5]. Performing a prostate biopsy in all men with a clinical screening positive PSA and/or DRE carries a significant public health burden, and harbours recognised clinical morbidity without definitive overall survival benefit for many. Hence, integration of MRI findings, importantly the lack of highly suspicious lesions, is of interest in RM assessment to determine which patients would be benefited most from prostate biopsy while sparing some from biopsy, without compromising detection of csPCa and oncological outcomes.

For patients who forgo prostate biopsy based upon factors such as nomogram‐predicted risk of harbouring csPCa, the appropriate timing for performing repeat evaluation with biomarkers and/or MRI is not well defined. Various models have shown much higher rates of biopsy avoidance if accepting some level of missed csPCa [6]. With the awareness that some men who would theoretically avoid a biopsy based on these RMs may actually harbour csPCa, should these men undergo repeat MRI as standard or would serial PSA assessment drive biopsy detection of their csPCa with adequate lead time for definitive treatment? Prospective investigations assessing the clinical course of patients with negative MRI findings who avoid or defer biopsy are critical to determine the real‐world applicability of such RMs. The true value of these RMs and nomograms should balance their public health cost and morbidity benefit with potential oncological risk.

by Zachary A. Glaser and Soroush Rais‐Bahrami

References

  1. Püllen LRadtke JPWiesenfarth M et al. External validation of novel magnetic resonance imaging‐based models for prostate cancer prediction. BJU Int 2020125407– 16
  2. Alberts ARRoobol MJVerbeek JFM et al. Prediction of high‐grade prostate cancer following multiparametric magnetic resonance imaging: improving the Rotterdam European randomized study of screening for prostate cancer risk calculators. Eur Urol 201975310– 8
  3. Radtke JPWiesenfarth MKesch C et al. Combined clinical parameters and multiparametric magnetic resonance imaging for advanced risk modeling of prostate cancer‐patient‐tailored risk stratification can reduce unnecessary biopsies. Eur Urol 201772888– 96
  4. Distler FARadtke JPBonekamp D et al. The value of PSA density in combination with PI‐RADS for the accuracy of prostate cancer prediction. J Urol 2017198575– 82
  5. Siddiqui MMRais‐Bahrami STurkbey B et al. Comparison of MR/ultrasound fusion‐guided biopsy with ultrasound‐guided biopsy for the diagnosis of prostate cancer. JAMA 2015313390– 7
  6. Mehralivand SShih JHRais‐Bahrami S et al. A Magnetic resonance imaging‐based prediction model for prostate biopsy risk stratification. JAMA Oncol 20184678– 85

 

 

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