Tag Archive for: #ProstateCancer

You are here: / #ProstateCancer

Posts

Article of the Week: Focal irreversible electroporation as primary treatment for localized prostate cancer

/by

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 the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Focal irreversible electroporation as primary treatment for localized prostate cancer

 

Willemien van den Bos*†‡, Matthijs J. Scheltema*†‡, Amila R. Siriwardana*†, Anton M.F. Kalsbeek*, James E. Thompson†, Francis Ting*†, Maret Bohm*,
Anne-Maree Haynes*, Ron Shnier§, Warick Delprado¶ and Phillip D. Stricker†

 

*Garvan Institute of Medical Research and Kinghorn Cancer Centre, †St Vincent’s Prostate Cancer Centre, Darlinghurst, NSW, Australia, ‡Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands, §Southern Radiology, Randwick, and Douglass Hanly Moir Pathology, Macquarie Park, NSW, Australia

 

Abstract

Objectives

To determine the safety, quality of life (QoL) and short‐term oncological outcomes of primary focal irreversible electroporation (IRE) for the treatment of localized prostate cancer (PCa), and to identify potential risk factors for oncological failure.

Patients and Methods

Patients who met the consensus guidelines on patient criteria and selection methods for primary focal therapy were eligible for analysis. Focal IRE was performed for organ‐confined clinically significant PCa, defined as high‐volume disease with Gleason sum score 6 (International Society of Urological Pathology [ISUP] grade 1) or any Gleason sum score of 7 (ISUP grades 2–3). Oncological, adverse event (AE) and QoL outcome data, with a minimum of 6 months’ follow‐up, were analysed. Patient characteristics and peri‐operative treatment variables were compared between patients with and without oncological failure on follow‐up biopsy. Wilcoxon’s signed rank test, Wilcoxon’s rank sum test and the chi‐squared test were used to assess statistically significant differences in paired continuous, unpaired continuous and categorical variables respectively.

Results

A total of 63 patients met all eligibility criteria and were included in the final analysis. No high‐grade AEs occurred. QoL questionnaire analysis demonstrated no significant change from baseline in physical (P = 0.81), mental (P = 0.48), bowel (P = 0.25) or urinary QoL domains (P = 0.41 and P = 0.25), but there was a mild decrease in the sexual QoL domain (median score 66 at baseline vs 54 at 6 months; P < 0.001). Compared with baseline, a decline of 70% in prostate‐specific antigen level (1.8 ng/mL, interquartile range 0.96–4.8 ng/mL) was seen at 6–12 months. A narrow safety margin (P = 0.047) and system errors (P = 0.010) were identified as potential early risk factors for in‐field oncological failure. In‐field and whole‐gland oncological control on follow‐up biopsies was 84% (38/45 patients) and 76% (34/45 patients); this increased to 97% (38/39 patients) and 87% (34/39 patients) when patients treated with a narrow safety margin and system errors were excluded.

Conclusion

Our data support the safety and feasibility of focal IRE as a primary treatment for localized PCa with effective short‐term oncological control in carefully selected men.

Read more articles of the week

Editorial: Has tailored, tissue‐selective tumour ablation in men with prostate cancer come of age?

/by

There are two principal challenges that face the growing number of clinical investigators that are evaluating tissue‐preserving therapies in men with prostate cancer.

The first is that every man’s prostate is different. So different and so unique are the personal attributes of a man’s prostate that it would, just like the iris or fingerprint, qualify as a unique identifier. It is just a few practical considerations that prevent it from doing so. This is a challenge that the clinician treating the liver, kidney or brain does not face – as these organs do not exhibit the between patient variability that we see in the prostate.

The second relates to within‐patient (or within‐prostate) differences. The nature of the tissue being treated will depend on which part of the prostate is being treated – peripheral, transition or central zone. Each of these zones will, in turn, be dependent on the age of the prostate, the extent of BPH, exhibit calcification and or cysts, and may or may not be infiltrated by acute and/or chronic inflammation.

These two sets of variability present considerable challenges to investigators that seek to selectively ablate a given zone of tissue, given that the nature of the target volume will be different in every man treated and exist in a context that is specific to the that man.

Add to this challenge the variability in prostate cancer tumour attributes – volume, location, heterogeneity (genetic, radiological, and histological), degree of immune infiltrate, and the extent of microscopic extension, we begin to get the picture 1.

The paper in this issue of the BJUI by van den Bos et al. 2 describes a modern attempt to overcome these challenges and attempt and achieve personalised care to individuals, their prostate glands, and their cancer.

The team used irreversible electroporation (IRE) to create a selective ablation zone around a given tumour volume, embracing a margin of 5–10 mm. This method of ablation has certain attributes that lend itself to the task. It can be applied to any zone of the prostate. It is not limited by the size of the prostate. It can create lesions of variable volume. The treatment is quick and therefore not overly affected by prostate gland swelling. Because the treatment uses an interstitial approach (needle based) the effectors of the treatment move with the prostate during respiration and changes in rectal fullness. These attributes mitigate most of the challenges generated by between‐patient variability.

The authors describe the methods by which they manage tumour‐specific differences. These important but rather technical constraints (to the non‐expert) comprise: tumour‐volume dependent variable needle load; individualised tissue impedance‐based energy adjustment; minimising variability in needle–needle distance; application of a 10‐mm margin; and near term verification of tissue change with post‐treatment MRI.

These conditions seem to have paid off. Although every patient underwent a treatment that was bespoke to both their prostate and their prostate cancer, the results were most promising for this truly personalised sub‐specialty of uro‐oncology.

The treatment was safe. There were no high‐grade adverse events reported in the 63 men included in the analysis. The disease‐specific and generic quality of life was not compromised by the range of interventions administered except in relation to the sexual quality of life domain that was marginally affected – a median score of 66 prior to therapy diminished to 54 when measured again 6‐months after treatment.

The authors managed to get a high proportion of men to undergo verification biopsy after treatment. From this they derived two oncological outcomes. These comprised freedom from clinically significant prostate cancer (high‐volume exclusive Gleason pattern 3 and/or any Gleason pattern 4 or 5) within and on the edge of field on the one hand and out of field on the other.

In patients who were free of any technical failure in relation to the administration of IRE and had a 10‐mm margin incorporated, the results were very promising with most of the patients evaluated free of disease both within (97% [38/39 men]) and out of field (87% [34/39 men]).

Although the numbers of patients reported upon are relatively small, the overall results represent a welcome improvement on previously published phase I clinical trial data using IRE, probably as a result of better patient selection and optimisation of energy delivery 3. The results, however, are reassuringly similar to previous case‐series that used alternative energy sources but were predicated on an anatomical‐based approach to tissue preservation 4. The tumour‐based approach reported upon by van den Bos et al. 2 is much more challenging as it exposes any subtle deficiencies in the base‐line risk‐stratification and imposes exacting constraints on the reliability of the energy source in creating irreversible cell kill where cell kill is intended.

Mark Emberton
Division of Surgery and Interventional Science, UCL, London, UK

 

References
  • 1 Linch M, Goh G, Hiley C et al. Intratumoural evolutionary landscape of high‐risk prostate cancer: the PROGENY study of genomic and immune parameters. Ann Oncol2017; 28: 2472–80

 

  • 2 van den Bos W, Scheltema MJ, Siriwardana AR et al. Focal irreversible electroporation as primary treatment for localized prostate cancer. BJU Int 2018; 121: 716–24

 

  • 3 Valerio M, Dickinson L, Ali A et al. Nanoknife electroporation ablation trial: a prospective development study investigating focal irreversible electroporation for localized prostate cancer. J Urol 2017; 197: 647–54

 

  • 4 Ahmed HU, Hindley RG, Dickinson L et al. Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study. Lancet Oncol 2012; 13: 622–32

 

Article of the Week: More PLND template at RP detects metastases in the common iliac region and in the fossa of Marcille

/by

Every Month, the Editor-in-Chief selects an Article of the Month 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 the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

More extended lymph node dissection template at radical prostatectomy detects metastases in the common iliac region and in the fossa of Marcille

 

Lydia Maderthaner, Marc A. Furrer, Urs E. Studer, Fiona C. Burkhard, George N. Thalmann and Daniel P. Nguyen

 

Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Read the full article

 

Abstract

Objectives

To assess the effect of adding lymph nodes (LNs) located along the common iliac vessels and in the fossa of Marcille to the extended pelvic LN dissection (PLND) template at radical prostatectomy (RP).

Patients and Methods

A total of 485 patients underwent RP and PLND at a referral centre between 2000 and 2008 (historical cohort: classic extended PLND template) and a total of 268 patients between 2010 and 2015 (contemporary cohort: extended PLND template including LNs located along the common iliac vessels and in the fossa of Marcille). Descriptive analyses were used to compare baseline, pathological, complication and functional data between the two cohorts. A logistic regression model was used to assess the template’s effect on the probability of detecting LN metastases.

Results

Of 80 patients in the historical cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 23 (29%), and the internal iliac in 18 (23%), while 39 patients (49%) had metastases in both locations. Of 72 patients in the contemporary cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 17 patients (24%), the internal iliac in 24 patients (33%), and the common iliac in one patient (1%), while 30 patients (42%) had metastases in >1 location (including fossa of Marcille in five patients). Among all 46 patients in the contemporary cohort with ≤2 metastases, three had one or both metastases in the common iliac region or the fossa of Marcille. The adjusted probability of detecting LN metastases was higher, but not significantly so, in the contemporary cohort. There were no differences between the two cohorts in complication rates and functional outcomes.

Conclusion

A more extended template detects LN metastases in the common iliac region and the fossa of Marcille and is not associated with a higher risk of complications; however, the overall probability of detecting LN metastases was not significantly higher.

Read more articles of the week

 

Article of the Week: The implications of baseline bone‐health assessment at initiation of androgen‐deprivation therapy for prostate cancer

/by

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 the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this month, it should be this one.

The implications of baseline bone‐health assessment at initiation of androgen‐deprivation therapy for prostate cancer

 

Peter S. Kirk* , Tudor Borza*, Vah akn B. Shahinian†, Megan E.V. Caram‡§, Danil V. Makarov**, Jeremy B. Shelton††, John T. Leppert‡‡§§, Ryan M. Blake*, Jennifer A. Davis§, Brent K. Hollenbeck*, Anne Sales§¶¶ and Ted A. Skolarus *§

 

*Dow Division of Health Services Research, Department of Urology, †Division of Nephrology, Department of Internal Medicine, ‡Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan Health System, §Veterans Affairs (VA) Health Services Research and Development, Center for Clinical Management Research, VA Ann Arbor Healthcare System, University of Michigan Medical School, Ann Arbor, MI, USA, Departments of Urology and Population Health, NYU Langone Medical Center, New York City, NY, USA, **VA New York Healthcare System, New York City, NY, USA, ††VA Greater Los Angeles Healthcare System, Los Angeles City, LA, USA, ‡‡Department of Urology, Stanford University School of Medicine, Stanford, CA, USA, §§VA Palo Alto Healthcare System, Palo Alto, CA, USA, and ¶¶Department of Learning Health Sciences, University of Michigan Medical School, Ann Arbor, MI, USA

 

Read the full article

Abstract

Objectives

To assess bone‐density testing (BDT) use amongst prostate cancer survivors receiving androgen‐deprivation therapy (ADT), and downstream implications for osteoporosis and fracture diagnoses, as well as pharmacological osteoporosis treatment in a national integrated delivery system.

Patients and methods

We identified 17 017 men with prostate cancer who received any ADT between 2005 and 2014 using the Veterans Health Administration cancer registry and administrative data. We identified claims for BDT within a 3‐year period of ADT initiation. We then used multivariable regression to examine the association between BDT use and incident osteoporosis, fracture, and use of pharmacological treatment.

Results

We found that a minority of patients received BDT (n = 2 502, 15%); however, the rate of testing increased to >20% by the end of the study period. Men receiving BDT were older at diagnosis and had higher‐risk prostate cancer (both P < 0.001). Osteoporosis and fracture diagnoses, use of vitamin D ± calcium, and bisphosphonates were all more common in men who received BDT. After adjustment, BDT, and to a lesser degree ≥2 years of ADT, were both independently associated with incident osteoporosis, fracture, and osteoporosis treatment.

Conclusions

BDT is rare amongst patients with prostate cancer treated with ADT in this integrated delivery system. However, BDT was associated with substantially increased treatment of osteoporosis indicating an underappreciated burden of osteoporosis amongst prostate cancer survivors initiating ADT. Optimising BDT use and osteoporosis management in this at‐risk population appears warranted.

Read more articles of the week

 

Editorial: Low rates of bone density testing in prostate cancer survivors on androgen‐deprivation therapy: where do we go from here?

/by

In this month’s issue of the BJU International, Kirk et al. 1 describe their findings regarding an important issue in the care of prostate cancer survivors on androgen‐deprivation therapy (ADT): the underuse of bone density testing (BDT) to screen for osteoporosis. ADT is the commonest systemic therapy in patients with prostate cancer, used in both metastatic and localised settings. Whilst it has clear survival benefits, ADT is also associated with harms including cardiovascular, cognitive, and metabolic side‐effects, as well as an increased risk of osteoporosis and fractures. These bone‐related complications are costly from a quality‐of‐life and financial perspective, especially given the critical importance of mobility in maintaining performance status and cardiovascular health during cancer treatment 2, 3. Consequently, most clinical practice guidelines include osteoporosis screening as a recommendation for men undergoing ADT.

In their study, ‘The implications of baseline bone health assessment at initiation of androgen‐deprivation therapy for prostate cancer’, the authors describe patterns of use of BDT and diagnosis of osteoporosis amongst men treated for prostate cancer in the USA Veterans Affairs (VA) system within a 3‐year period following ADT initiation. There was a statistically significant increase in the BDT rate throughout the study period; however, overall BDT remains uncommon amongst patients with prostate cancer on ADT, used in only 15% of men in their cohort. Unsurprisingly, patients who received BDT were more likely to be diagnosed with osteoporosis, be diagnosed with a fracture, and receive treatment with vitamin D, calcium and bisphosphonates. The authors acknowledge an important limitation about the applicability of their VA study to the civilian health population. However, given that the VA and military health systems perform as well, if not better, on several important metrics in prostate cancer care 4, 5, these results should not be ignored simply because they were obtained in the military health system.

The increase in BDT screening throughout the study may be attributable to increased awareness of guidelines published during the study period. However, the overall BDT rate remains low. This may be explained by insufficient access, lack of information technology, as well as more nebulous aspects of care such as physician culture, beliefs, and habits 6.

Studies such as this are vital to identify opportunities for improving care delivery. What are needed next are innovations to optimise the delivery of care for patients treated with ADT. Whilst improving BDT adherence may lack the cachet of next‐generation targeted therapies, this is an example of the kind of simple, measurable area where improvement in care delivery systems may yield large benefits.

There are many possible avenues for success: quality improvement collaboratives are one well‐known innovation, which may be applicable to this area: examples, such as the Michigan Urological Surgery Improvement Collaborative (MUSIC) and the AUA Quality Registry (AQUA) are success stories, but to our knowledge there are no published studies specifically attempting to improve adherence to BDT guidelines within these cohorts. Other practice‐based innovations include navigators and multidisciplinary cancer teams, either of which may yield improvements in guideline adherence. Online patient support groups can raise awareness. And although we all know how electronic reminders have frustrated countless physicians, electronic reminders about recommended tests and interventions may be an important tool. At our institution, a Prostate Cancer Foundation grant is funding the development of a mobile health app, which is targeted exclusively at men receiving ADT for prostate cancer. This app will encourage physical activity and healthy eating, which can both support bone health.

In our view, the issue of bone screening is a clear example of where innovative strategies to improve care delivery and guideline adherence may make a big difference for men living with prostate cancer. We look forward to seeing more in the years to come.

 

Sabrina S. Harmouch, Alexandra J. Berger, and Alexander P. Cole

 

Center for Surgery and Public Health, Division of Urological Surgery, Brigham and Wo men’s Hospital, Harvard Medical School, Boston, MA, USA

 

References
  • 1 Kirk PS, Borza T, Shahinian VB et al. The implications of baseline bone‐health assessment at initiation of androgen‐deprivation therapy for prostate cancer. BJU Int2018; 121: 558–64

 

 

 

  • 4 Cole AP, Jiang W, Lipsitz SR et al. The use of prostate specific antigen screening in purchased versus direct care settings: data from the TRICARE® military database. J Urol 2017; 198: 1295–300

 

  • 5 Cullen J, Brassell SA, Chen Y et al. Racial/Ethnic patterns in prostate cancer outcomes in an active surveillance cohort. Prostate Cancer 2011; 2011: 234519

 

 

Article of the Month: MEAL Study – Effects of Diet in PCa Patients on AS

/by

Every Month, the Editor-in-Chief selects an Article of the Month 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 the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this month, it should be this one.

Men’s Eating and Living (MEAL) study (CALGB 70807 [Alliance]): recruitment feasibility and baseline demographics of a randomized trial of diet in men on active surveillance for prostate cancer

J. Kellogg Parsons*†‡ , John P. Pierce§, James Mohler¶, Electra Paskett**, Sin-Ho Jung††, Michael J. Morris‡‡, Eric Small§§, Olwen Hahn¶¶, Peter Humphrey***, John Taylor††† and James Marshall†††

*Division of Urologic Oncology, UC San Diego Moores Comprehensive Cancer Center, La Jolla, CA, USA, †Department of Urology, UC San Diego Health System, La Jolla, CA, USA, ‡VA San Diego Healthcare System, La Jolla, CA, USA, §Department of Family Medicine and Public Health and Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA, ¶Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA, **Department of Medicine, College of Medicine, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA, ††Alliance Statistics and Data Center, Duke University, Durham, NC, USA, ‡‡Memorial Sloan Kettering Cancer Center, New York, NY, USA, §§UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA, ¶¶Alliance Central Protocol Operations, University of Chicago, Chicago, IL, USA, ***Department of Pathology, Yale University Medical School, New Haven, CT, USA, and †††Department of Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY, USA J. Protocol Operations, University of Chicago, Chicago, IL, USA, ***Department of Pathology, Yale University Medical School, New Haven, CT, USA, and †††Department of Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY, USA

 

Read the full article

Abstract

Objective

To assess the most recommended books on keto and the feasibility of performing national, randomized trials of dietary interventions for localized prostate cancer.

Methods

The Men’s Eating and Living (MEAL) study (CALGB 70807 [Alliance]) is a phase III clinical trial testing the efficacy of a high‐vegetable diet to prevent progression in patients with prostate cancer on active surveillance (AS). Participants were randomized to a validated diet counselling intervention or to a control condition. Chi‐squared and Kruskal–Wallis analyses were used to assess between‐group differences at baseline.

Results

Between 2011 and 2015, 478 (103%) of a targeted 464 patients were randomized at 91 study sites. At baseline, the mean (sd) age was 64 (6) years and mean (sd) PSA concentration was 4.9 (2.1) ng/mL. Fifty‐six (12%) participants were African‐American, 17 (4%) were Hispanic/Latino, and 16 (3%) were Asian‐American. There were no significant between‐group differences for age (P = 0.98), race/ethnicity (P = 0.52), geographic region (P = 0.60), time since prostate cancer diagnosis (P = 0.85), PSA concentration (P = 0.96), clinical stage (T1c or T2a; P = 0.27), or Gleason sum (Gleason 6 or 3+4 = 7; P = 0.76). In a pre‐planned analysis, the baseline prostate biopsy samples of the first 50 participants underwent central pathology review to confirm eligibility, with an expectation that <10% would become ineligible. One of 50 participants (2%) became ineligible.

Conclusion

The MEAL study shows the feasibility of implementing national, multi‐institutional phase III clinical trials of diet for prostate cancer and of testing interventions to prevent disease progression in AS.

Read more articles of the week

Editorial: PCa Prevention – Proof is Elusive

/by

Prevention is so much better than cure because it saves the labor of being sick. Thomas Adams, 1618

Inferior doctors treat the full blown disease; mediocre doctors treat the disease before evident; superior doctors prevent disease.   Nai Ching, 1st Chinese Medical Text, 2600 BC. 

Enthusiasm for prevention is hundreds, even thousands of years old.  In the field of prostate cancer, profound differences in the regional variation of prostate cancer around the world (highest in Americans and Scandinavians, lowest in Asians) despite the similar incidence of histologic occult prostate cancer, and shifts in the incidence in mortality amongst immigrant populations moving from low to high prostate cancer regions, led to a firm belief that clinical disease was preventable.   This belief was supported by the known long initiation phase for prostate cancer, providing an opportunity over decades for diet and micronutrient intake to influence the likelihood of disease progression.

In addition, many epidemiologic studies pointed to the benefits of fruits and vegetable intake high in Vitamin E, Selenium, Beta Carotene, Lycopene, and other micronutrients, and a diet low in animal fat.

However, recently several pivotal studies have taken the bloom off the rose of prevention.  In particular, the SELECT study demonstrated a 17% increased rate of prostate cancer in men on Vitamin E, and an increase in DM in men on Selenium (1).  The study was resoundingly negative.  In addition, both high intake of multivitamins, and high dairy and calcium intake, have been associated with an increased risk of fatal prostate cancer (2).   Folic acid intake results in an increased incidence of prostate cancer.  Despite the positive PCPC and Reduce trials, the 5 ARIs were not approved for prevention by the FDA due to concerns about an increased risk of high grade prostate cancer, despite the reduction in positive biopsies in men on the drug (mostly due to  a decrease in low grade cancer).

Further, studies of the association between dietary intake of fruits and vegetables and PCa are inconsistent.  For example, one large study of 130,544 men found no significant association between fruit or vegetable intake, including cruciferous vegetables, and prostate cancer. (3)  Another study showed dietary modification, reducing fat and increasing fruits, vegetables, and fiber, had no impact on PSA.  (4).

And yet, despite the negative intervention studies, a lingering spark of hope exists that the many positive population, epidemiologic, and pre- clinical studies supporting dietary prevention will be vindicated.  The study in the current issue of BJU Int on the MEAL study is therefore a laudable and ambitious initiative (5).   Remarkably, 478 men have been randomized to validated dietary counseling intervention vs no intervention.  This paper reports the initial demographics and eligibility data.  It is undoubtedly the first of many publications that will arise from this important trial.

Will this study prove its’ ambitious goal, to demonstrate that prostate cancer progression can be influenced by dietary modification?   While the initiative is laudable, I suspect the hurdles are insurmountable given the sample size and conceptual basis for the study.  The study is being performed in men on active surveillance, and the primary end point will be the risk of disease ‘progression’.  The study references the Redeem study, which showed a 44% reduction in disease ‘progression’ with dutasteride compared to placebo (6).

What we have learned since the Redeem study was initiated more than a decade ago was that the major limitation of conservative management in men diagnosed with low grade prostate cancer on systematic biopsy is not disease progression as it is usually defined (ie, developing worse disease over time); it is grade misattribution, based on sampling and pathologic miss of co-existent higher grade cancer (7).  Higher grade cancer is present in about 30% of men with Gleason 6 cancer on systematic biopsy.  Finding this on subsequent systematic biopsy is largely a matter of luck, location of the cancer, and biopsy strategy and number.    In contrast, true grade progression (from Gleason pattern 3 to pattern 4 or 5) is uncommon, estimated to occur in only 1-2% of patients per year (8).  The adoption of MRI and targeted biopsy into the surveillance algorithm has reduced the misattribution problem.   Thus, the true ‘event rate’ (exclusive of misattribution) is likely to be in the 15% range at 10 years.   A study with the power to detect a 20% relative difference in these events, ie a 3% absolute difference, would require more than a thousand patients followed for 10 years.

In the Redeem study, the reduction in ‘progression’ was entirely related to a decrease in the volume of low grade cancer.  Indeed, the rate of upgrading was 13% in both arms in Redeem.  Therefore the decrease in progression in that study likely reflected the cytoreduction effect of 5 ARIs, and not a real biological effect on cancer progression.

Thus, to be meaningful, prevention studies in men on surveillance should identify, at the very least, a real reduction in grade progression, based on state of the art evaluation at baseline with MRI and targeted biopsies as warranted, and long term follow up.    A decrease in the rate of volume progression of Gleason 6, a major end point of this study, is not meaningful.   In the study as described, which does not explicitly incorporate MRI, an imbalance in the number of patients having off protocol MRI and targeted biopsies between the two arms could significantly bias the outcome.

A further problem with long term studies of dietary intervention relates to the well-known methodological limitations in this area—ensuring long term compliance, recall bias of food intake, and contamination of the control arm.

Nonetheless, the authors deserve strong congratulations for pursuing this major initiative.  We will follow the course of this study with interest.

 

Dr. Laurence Klotz C.M.

Division of Urology, Sunnybrook Health Sciences Centre, 2075 Bayview Ave. #MG408 

Toronto, Ontario M4N 3M5

 

Read the full article

 

References

  1. Klein EA, Thompson IM Jr, Tangen CM, et al.: Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306 (14): 1549-56, 2011
  2. Lawson KA, Wright ME, Subar A, et al.: Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 99 (10): 754-64, 2007
  3. Key TJ, Allen N, Appleby P, et al.: Fruits and vegetables and prostate cancer: no association among 1104 cases in a prospective study of 130544 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 109 (1): 119-24, 2004
  4. Shike M, Latkany L, Riedel E, et al.: Lack of effect of a low-fat, high-fruit, -vegetable, and -fiber diet on serum prostate-specific antigen of men without prostate cancer: results from a randomized trial. J Clin Oncol 20 (17): 3592-8, 2002.
  5. BJU-2016-1793.R2 – The Men’s Eating and Living (MEAL) Study (CALGB 70807 [Alliance]): Recruitment Feasibility and Baseline Demographics of a Randomized Trial of Diet in Men on Active Surveillance for Prostate Cancer
  6. Fleshner NE, Lucia MS, Egerdie B, et al. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. 2012;379(9821):1103-1111.
  7. Cooperberg MR, Carroll PR, Klotz L: Active surveillance for prostate cancer: progress and promise. J Clin Oncol 29 (27): 3669-76, 2011. [PubMed]
  8. Lurdes Y.T. Inoue, Bruce J. Trock, Alan W. Partin, H. Ballentine Carter, Ruth Etzioni Modeling Grade Progression In An Active Surveillance Study Stat Med. Author manuscript; available in PMC 2015 Mar 15. Published in final edited form as: Stat Med. 2014 Mar 15; 33(6): 930–939.

 

Article of the Week: Chitosan membranes applied on the prostatic neurovascular bundles after nerve‐sparing robot‐assisted radical prostatectomy: a phase II study

/by

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 the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this month, it should be this one.

Chitosan membranes applied on the prostatic neurovascular bundles after nerve‐sparing robot‐assisted radical prostatectomy: a phase II study

Francesco Porpiglia* , Riccardo Bertolo*, Cristian Fiori*, Matteo Manfredi*, Sabrina De Cillis* and Stefano Geuna†

 

*Division of Urology, Department of Oncology, and †Department of Clinical and Biological Sciences, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy

 

Read the full article

Abstract

Objective

To evaluate the feasibility and the safety of applying chitosan membrane (ChiMe) on the neurovascular bundles (NVBs) after nerve‐sparing robot‐assisted radical prostatectomy (NS‐RARP). The secondary aim of the study was to report preliminary data and in particular potency recovery data.

Patients and Methods

This was a single‐centre, single‐arm prospective study, enrolling all patients with localised prostate cancer scheduled for RARP with five‐item version of the International Index of Erectile Function scores of >17, from July 2015 to September 2016. All patients underwent NS‐RARP with ChiMe applied on the NVBs. The demographics, perioperative, postoperative and complications data were evaluated. Potency recovery data were evaluated in particular and any sign/symptom of local allergy/intolerance to the ChiMe was recorded and evaluated.

Results

In all, 140 patients underwent NS‐RARP with ChiMe applied on the NVBs. Applying the ChiMe was easy in almost all the cases, and did not compromise the safety of the procedure. None of the patients reported signs of intolerance/allergy attributable to the ChiMe and potency recovery data were encouraging.

Conclusion

In our experience, ChiMe applied on the NVBs after NS‐RARP was feasible and safe, without compromising the duration, difficulty or complication rate of the ‘standard’ procedure. No patients had signs of intolerance/allergy attributable to the ChiMe and potency recovery data were encouraging. A comparative cohort would have added value to the study. The present paper was performed before Conformité Européene (CE)‐mark achievement.

Read more articles of the week

Article of the Week: Prospective randomised non-inferiority trial of PD placement vs ND placement after RARP

/by

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 the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this month, it should be this one.

Prospective randomised non-inferiority trial of pelvic drain placement vs no pelvic drain placement after robot-assisted radical prostatectomy

Avinash Chenam* , Bertram Yuh*, Ali Zhumkhawala*, Nora Ruel†, William Chu*, Clayton Lau*, Kevin Chan*, Timothy Wilson* and Jonathan Yamzon*

 

*Department of Surgery, Division of Urology and Urologic Oncology , and †Department of Biostatistics, City of Hope National Medical Center, Duarte, CA, USA

 

Read the full article

Abstract

Objective

To determine if eliminating the prophylactic placement of a pelvic drain (PD) after robot-assisted radical prostatectomy (RARP) affects the incidence of early (90-day) postoperative adverse events.

Patients and Methods

In this parallel-group, blinded, non-inferiority trial, we randomised patients planning to undergo RARP to one of two arms: no drain placement (ND) or PD placement. Patients with demonstrable intraoperative leakage upon bladder irrigation were excluded. Randomisation sequence was determined a priori using a computer algorithm, and included a stratified design with respect to low vs intermediate/high D’Amico risk classifications. Surgeons remained blinded to the randomisation arm until final eligibility was verified at the end of the RARP. The primary endpoint was overall incidence of 90-day complications which, based on our standard treatment using PD retrospectively, was estimated at 13%. The non-inferiority margin was set at 10%, and the planned sample size was 312. An interim analysis was planned and conducted when one-third of the planned accrual and follow-up was completed, to rule out futility if the delta margin was in excess of 0.1389.

Results

From 2012 to 2016, 189 patients were accrued to the study, with 92 patients allocated to the ND group and 97 to the PD group. Due to lower than expected accrual rates, accrual to the study was halted by regulatory entities, and we did not reach the intended accrual goal. The ND and PD groups were comparable for median PSA level (6.2 vs 5.8 ng/mL, P = 0.5), clinical stage (P = 0.8), D’Amico risk classification (P = 0.4), median lymph nodes dissected (17 vs 18, P = 0.2), and proportion of patients receiving an extended pelvic lymph node dissection (70.7% vs 79.4%, P = 0.3). Incidence of 90-day overall and major (Clavien–Dindo grade >III) complications in the ND group (17.4% and 5.4%, respectively) was not inferior to the PD group (26.8% and 5.2%, respectively; P < 0.001 and P = 0.007 for difference of proportions <10%, respectively). Symptomatic lymphocoele rates (2.2% in the ND group, 4.1% in the PD group) were comparable between the two arms (P = 0.7).

Conclusions

Incidence of adverse events in the ND group was not inferior to the group who received a PD. In properly selected patients, PD placement after RARP can be safely withheld without significant additional morbidity.

Read more articles of the week

 

USANZ 2018: Melbourne

/by

G’day! The 71st  annual USANZ Congress, was held in Melbourne and had the biggest attendance on record for the past 6 years. The Urological Nurse’s congress: ANZUNS ran concurrently, encouraging multi disciplinary learning. An excellent and varied educational programme was masterminded by Declan Murphy, Nathan Lawrentschuk and their organising committee. Melbourne provided a great backdrop and soon felt like home with a rich and busy central business district, cultural and sporting venues, the Yarra river flowing past the conference centre, edgy graffiti and hipster coffee shops, plus too many shops, bars and restaurants to visit.

The programme included a day of masterclasses on a range of subjects, including: urological imaging, advanced robotic surgery with a live case from USC, metastatic prostate cancer and penile prosthetics. These were well attended by trainees and consultants alike. The PCNL session (pictured) with Professor Webb was popular and he generously gave his expertise.  The session was supported by industry and provided an opportunity to use the latest nephroscopes on porcine models and innovative aids to realistically practice different puncture techniques.

Two plenary sessions were held each morning covering the breadth and depth of urology and were well attended. Dr Sotelo is always a highlight; he presented, to an auditorium of collective gasps, a unique selection of ‘nightmare’ cases  His cases gave insight in how intraoperative complications occur and how they can be avoided.  Tips, such as zooming out to reassess in times of anatomical uncertainty during laparoscopy or robotic surgery have great impact when you witness the possible consequences. Tim O’Brien shared his priceless insights on performing IVC thrombectomy highlighting the need for preoperative planning, early control of the renal artery and consideration of pre-embolisation.  His second plenary on retroperitoneal fibrosis provided clarity on the management of this rare condition highlighting the role of PET imaging and, as with complex upper tract surgery, the importance of a dedicated team.

Tony Costello’s captivating presentation covered several myths in robotic prostate surgery, plus the importance of knowing your own outcome figures and a future where robotics will be cost equivalent to laparoscopy. Future technology, progress in cancer genomics and biomarkers were also discussed in various sessions.  One example of new technology was Aquablation of the prostate; Peter Gilling presented the WATER trial results suggesting non-inferiority to TURP.  A welcome addition to the programme was Victoria Cullen (pictured), a psychologist and Intimacy Specialist who provides education, support and strategies for sexual  rehabilitation. She described her typical consultation with men with sexual dysfunction and how to change worries about being ‘normal’ to focusing on what is important to the individual.

Joint plenary sessions with the AUA and EAU were a particular highlight. Prof Chris Chapple confirmed the need for robust, evidence guidelines which support clinical decision making; and in many cases can be used internationally. He suggested collaboration is crucial between us as colleagues and scientists working in the field of urology. Stone prevention and analysis of available evidence was described by Michael Lipkin; unfortunately stone formers are usually under-estimaters of their fluid intake so encouragement is always needed! Amy Krambeck presented evidence for concurrent use of anticoagulants and antiplatelets during BOO surgery and suggested there can be a false sense of security when stopping these medications as it isn’t always safe. She championed HoLEP as her method of BOO surgery and continues medications, although the evidence does show blood transfusion rate may be higher. She also uses a fluid warming device which has less bleeding and therefore improved surgical vision; importantly it is preferred by her theatres nurses! MRI of the prostate was covered  by many different speakers, however Jochen Walz expertly discussed the limitations of MRI in particular relating negative predictive value (pictured). He eloquently explained the properties of cribiform Gleason 4 prostate cancer and how this variant contributed to the incidence of false negatives.

Moderated poster and presentation sessions showcased research and audit projects from the UK, Australia, New Zealand and beyond, mainly led by junior urologists. The best abstracts submitted by USANZ trainees were invited to present for consideration of Villis Marshall and Keith Kirkland prizes. These prestigious prizes were valiantly fought for and reflected high quality research completed by the trainees. Projects included urethral length and continence, no need for lead glasses, obesity and prostate cancer, multi-centre management of ureteric calculi, mental health of surgical trainees and seminal fluid biomarkers in prostate cancer. This enthusiasm for academia will undoubtedly stand urology in good stead for the future; this line up (pictured) is one to watch!

The Trade hall provided a great networking space to be able to meet with friends and colleagues and engage with industry. It also hosted poster presentation sessions, with a one minute allocation for each presenter – which really ensures a succinct summary of the important findings (pictured)! It was nice to meet with Australian trainees and we discussed the highs and lows of training and ideas for fellowships. Issues such as clinical burden and operative time, selection into the specialty, cost of training, burn out and exam fears were discussed and shared universally; however there is such enthusiasm, a passion for urology and inspirational trainers which help balance burdens that trainees face. Furthermore, USANZ ‘SET’ Trainees were invited to meet with the international faculty in a ‘hot seat’ style session which was an enviable opportunity to discuss careers and aspirations.

In addition to the Congress I was fortunate to be invited for a tour and roof-top ‘barbie’ at the Peter Mac Cancer centre; plus a visit to Adelaide with Rick (Catterwell, co-author) seeing his new hospital and tucking into an inaugural Aussie Brunch. Peter Mac and Royal Adelaide Hospital facilities indicated an extraordinary level of investment made by Federal and State providers; the Peter Mac in particular had impressive patient areas, radiotherapy suites and ethos of linking clinical and research. However beyond glossy exteriors Australian public sector clinicians voiced concerns regarding some issues similar to those we face in the NHS.

Despite the distance of travelling to Melbourne and the inevitable jet lag the world does feels an increasingly smaller place and the Urological world even more so. There is a neighbourly relationship between the UK, Australia and New Zealand as evidenced by many familiar faces at USANZ who have worked between these countries; better for the new experiences and teaching afforded to them by completing fellowships overseas. The Gala Dinner was a great chance to unwind, catch up with friends and celebrate successes in the impressive surrounding of Melbourne Town Hall (pictured); the infamous organ played particularly rousing rendition of Phantom of the Opera on arrival.

The enthusiasm to strive for improvement is similar both home and away and therefore collaboration both nationally and internationally is integral for the progress of urology. The opening address by USANZ President included the phrase ‘together we can do so much more’ and this theme of collaboration was apparent throughout the conference. The future is bright with initiatives led by enthusiastic trainee groups BURST and YURO to collect large volume, high quality data from multiple centres, such as MIMIC which was presented by Dr Todd Manning. Social media, telecommunications and innovative technology should be used to further the specialty, especially with research and in cases of rare diseases – such as RPF.  Twitter is a tool that can be harnessed and was certainly used freely with the hashtag #USANZ18. Furthermore, utilisation of educational learning platforms such as BJUI knowledge and evidence based guidelines help to facilitate high quality Urological practice regardless of state or country.

So we’d like to extend a huge thank you to Declan, Nathan and the whole team, and congratulate them for a successful, educational and friendly conference; all connections made will I’m sure last a lifetime and enable us to do more together.

Sophie Rintoul-Hoad and Rick Catterwell

 

© 2024 BJU International. All Rights Reserved.