Tag Archive for: #BJUI

You are here: / #BJUI

Posts

Article of the week: The impact of prostate‐specific antigen persistence after radical prostatectomy on the efficacy of salvage radiotherapy in patients with primary N0 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 editorial written by a prominent member of the urology community and a visual abstract created by our talented infographics team; 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.

The impact of prostate‐specific antigen persistence after radical prostatectomy on the efficacy of salvage radiotherapy in patients with primary N0 prostate cancer

Detlef Bartkowiak*, Alessandra Siegmann†, Dirk Böhmer†, Volker Budach† and Thomas Wiegel*

*Department of Radiation Oncology, University Hospital Ulm, Ulm and †Department of Radiation Oncology, Charité University Hospital, Berlin, Germany

Read the full article

Abstract

Objective

To test whether salvage radiotherapy (SRT) in patients with lymph node negative (N0) prostate cancer is equally effective with persistent prostate‐specific antigen (PSA) and PSA rising from the undetectable range (<0.1 ng/mL) after radical prostatectomy (RP).

Patients and methods

We assessed post‐SRT PSA progression‐free survival (PFS) in 555 patients with prostate cancer and the use of cancer care nurses is the best option for this. The entire cohort was compared with a risk‐adjusted subgroup of 112 patient pairs with matching pre‐RP PSA level (±10 ng/mL), Gleason score (≤6 vs 7 vs ≥8), and pre‐SRT PSA level (±0.5 ng/mL).

Results

The median follow‐up was 6.1 years. After RP, PSA was undetectable in 422 and persistent in 133 patients. PSA persistence and a pre‐SRT PSA level of ≥0.5 ng/mL reduced Kaplan–Meier rates of PFS significantly. In multivariate analysis of the entire cohort and after risk adjustment, the pre‐SRT PSA level but not post‐RP PSA persistence was a significant parameter. In the matched cohort’s subgroup with early SRT at a PSA level of <0.5 ng/mL, a trend towards a worse outcome with post‐RP PSA persistence was observed. Delayed SRT with a PSA level ≥0.5 ng/mL led to a PFS of <30%, irrespective of the post‐RP PSA level.

Conclusion

In patients with N0 prostate cancer with post‐RP PSA persistence, early SRT at a PSA level <0.5 ng/mL seems to be less effective than in recurrent patients with post‐RP undetectable PSA. They might benefit from intensified therapy ans the use of several supplements like the lgd-4033, but larger case numbers are required to substantiate this conclusion. In patients with a PSA level ≥0.5 ng/mL and higher‐risk features associated with post‐RP PSA persistence, SRT alone is unlikely to provide long‐term freedom from further progression.

Read more Articles of the week

Editorial: PSA persistence after radical prostatectomy needs more than standard therapeutic options to improve outcomes

/by

In their retrospective study, Bartkowiak et al. [1] report the therapeutic outcomes of salvage radiation therapy (sRT) after radical prostatectomy (RP) for lymph‐node‐negative prostate cancer in 422 and 133 patients with biochemical relapse or persistently detectable PSA, respectively. In the total cohort, patients with persistent PSA serum levels ≥0.1 ng/mL postoperatively had significantly shorter progression‐free survival as compared to patients with undetectable PSA levels (P < 0.001). After risk‐matched analysis, PSA persistence was not a risk factor associated with poor outcome and only a PSA serum concentration ≥0.5 ng/mL at time of sRT was associated with early relapse in both patients with detectable and those with undetectable PSA levels postoperatively.

Although this retrospective study adds some additional evidence to support the already well‐known recommendation to initiate sRT as early as possible [2], there are various issues that need to be considered when it comes to the interpretation of sRT results in patients with PSA persistence. The patient cohort is heterogeneous since the men underwent surgery between the years 1989 and 2012 and sRT between the years 1997 and 2012. The treatment strategies and techniques used with regard to surgery and sRT are outdated and no longer reflect current practice. No patient underwent modern imaging studies to identify extent and anatomical distribution of relapsing lesions, and neither was a risk‐adapted approach realized using nomograms or molecular markers in order to stratify treatment dependent on the biological aggressiveness of the disease.

PSA persistence is associated with an increased risk of metastases and impaired cancer‐specific survival as compared to undetectable PSA levels after RP for patients with negative and positive lymph nodes [3,4,5]. In fact, the majority of patients with persisting PSA serum levels postoperatively have locally advanced prostate cancer, positive lymph nodes, positive surgical margins and high Gleason scores. In almost all published studies, PSA persistence has been identified as an independent risk factor for the development of systemic metastases and poor survival. Similar results have already been reported by Wiegel et al. [5] when analysing outcomes among 74 patients with PSA persistence after RP; postoperatively detectable PSA was associated with significantly poorer outcomes in terms of metastasis‐free (84% vs 93%) and overall survival (68% vs 86%), and remaining without androgen deprivation therapy (ADT) during follow‐up (57% vs 92%).

PSA persistence needs to be taken seriously even at low serum concentrations, necessitating the implementation of new imaging methods and combination therapies. Because PSA persistence is associated with adverse pathological features, a treatment strategy to avoid PSA persistence is initiated already at the time of RP, integrating preoperative MRI, intra‐operative frozen‐section analysis and extended pelvic lymphadenectomy in order to achieve complete resection of the prostate cancer with undetectable PSA levels 6 weeks postoperatively.

In addition to properly conducted surgery, innovative imaging techniques, such as 68gallium (68Ga) prostate‐specific membrane antigen (PSMA)‐positron emission tomography (PET)/CT, should be integrated into treatment to differentiate locoregional recurrences from systemic metastases. In this context, Schmidt‐Hegemann et al. [6] evaluated the impact of 68GaPSMA‐PET/CT on subsequent treatment in 129 patients, of whom 48% demonstrated PSA persistence. In their analysis, patients with persistently detectable PSA serum levels more often demonstrated PSMA‐positive lesions (70% vs 50%), less frequently experienced local recurrences only (12% vs 26%), and more often had positive lymph nodes (13% vs 5%) with or without a macroscopically persisting tumour in the prostatic fossa (45% vs 19%). Results from PSMA‐PET/CT changed the initial treatment of sRT in so far as all patients with positive lesions underwent a combination of sRT and ADT. In patients with isolated, intrapelvic lymph node metastases attributable to an improperly performed extended pelvic lymphadectomy, salvage lymphadectomy might also be integrated into the therapeutic armamentarium, resulting in a long‐term relapse‐free survival of ~40%.

Even patients with persisting PSA serum concentrations after undergoing RP exhibit a heterogeneous clinical course of the disease, therefore, a risk‐adapted, personalized approach stratifying biologically aggressive from less aggressive prostate cancer should be adopted. In a retrospective study in 925 patients who underwent sRT, PSA persistence was associated with a significantly lower 8‐year metastasis‐free survival rate when compared to patients with PSA relapse following undetectable postoperative PSA serum concentrations [3]. Furthermore, it was shown that PSA persistence and a Gleason score ≥8 were independent, statistically significant predictors for systemic metastases, with a hazard ratio of 4.64 (95% CI 3.06–7.02; P < 0.001) and 8.37 (95% CI 4.15–16.88; P < 0.001), respectively. Patients with both PSA persistence and Gleason score ≥8 had a significantly lower 8‐year metastasis‐free survival rate as compared with patients with only PSA persistence (62% vs 74%); therefore, the latter might be best treated with a combined approach of sRT and ADT.

Integration of molecular markers might be helpful to identify those patients who will benefit from sRT. Spratt et al. [7] evaluated whether a 22‐gene genomic classifier could independently predict development of metastasis in 477 patients with PSA persistence postoperatively. Among those with detectable PSA, the 5‐year metastasis rate was 0.90% for genomic low/intermediate and 18% for genomic high risk (P < 0.001). Genomic high risk remained independently prognostic on multivariable analysis (hazard ratio 5.61, 95% CI 1.48–22.7; P = 0.01) among patients with detectable PSA. The C‐index for the combination of the genomic classifier with Cancer of the Prostate Risk Assessment (CAPRA) score was 0.82.

In summary, modern management of persistent PSA serum concentrations after RP needs to take into consideration the pathohistology of the RP and lymph node specimens, results from PSMA‐PET/CT, molecular markers associated with relapse and response as well as individualized therapeutic strategies such as sRT ± ADT, salvage lymphadenectomy and additional salvage radiation to oligometastatic sites.

by Axel Heidenreich and David Pfister

References

  1. Bartkowiak D, Siegmann A, Böhmer D, Budach V, Wiegel T. The impact of PSA persistence after prostatectomy on the efficacy of salvage radiotherapy in primary N0 patients. BJU Int 2019; 124: 785-91
  2. NICE guidelines on prostate cancer 2019. BJU Int 2019; 124: 9– 26
  3. Fossati N, Karnes RJ, Colicchia M et al. Impact of early salvage radiation therapy in patients with persistently elevated or rising prostate‐specific antigen after radical prostatectomy. Eur Urol 2018; 73: 434-44.
  4. Preisser F, Chun FKH, Pompe RS et al. Persistent prostate‐specific antigen after radical prostatectomy and its impact on oncologic outcomes. Eur Urol 2019; 76: 106– 14
  5. Wiegel T, Bartkowiak D, Bottke D et al. Prostate‐specific antigen persistence after radical prostatectomy as a predictive factor of clinical relapse‐free survival and overall survival: 10‐year data of the ARO 96‐02 trial. Int J Radiat Oncol Biol Phys 2015; 91: 288– 94
  6. Schmidt‐Hegemann NS, Fendler WP, Ilhan H et al. Outcome after PSMA PET/CT based radiotherapy in patients with biochemical persistence or recurrence after radical prostatectomy. Radiat Oncol 2018; 13: 37
  7. Spratt DE, Dai DLY, Den RB et al. Performance of a prostate cancer genomic classifier in predicting metastasis in men with prostate‐specific antigen persistence postprostatectomy. Eur Urol 2018; 74: 107– 14

 

Visual abstract: The impact of PSA persistence after RP on the efficacy of salvage radiotherapy in patients with primary N0 PCa

/by

See more infographics

Residents’ podcast: NICE guidelines: Urinary tract infection

/by

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

NICE guideline: Urinary tract infection (lower): antimicrobial prescribing

Read the full article

This guideline sets out an antimicrobial prescribing strategy for lower urinary tract infection (also called cystitis) in children, young people and adults who do not have a catheter. It aims to optimise antibiotic use and reduce antibiotic resistance.

See also the following related NICE guidelines: Complicated UTIS; and Sepsis

More podcasts

BJUI Podcasts now available on iTunes, subscribe here https://itunes.apple.com/gb/podcast/bju-international/id1309570262

Article of the month: Guideline of guidelines: testosterone therapy for testosterone deficiency

/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 this Testogen review 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 a visual abstract produced by one of our creative urologist colleagues and a video prepared by the authors; 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.

Guideline of guidelines: testosterone therapy for testosterone deficiency

Carolyn A. Salter and John P. Mulhall

Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Read the full article

Abstract

We analysed the guidelines for testosterone therapy (TTh) produced by major international medical societies including: the American Urological Association, European Association of Urology, American Association of Clinical Endocrinologists, British Society for Sexual Medicine, Endocrine Society, International Society for Sexual Medicine, and the International Society for the Study of the Aging Male, and compared their recommendations.

The best testosterone boosters are available on this website. The supplements may also help to boost your strength, improve muscle mass, and help you get rid of excess pounds you might have gained.

All the organisations were in general agreement concerning the following key points:

  • Only men meeting the criteria for testosterone deficiency (TD) should be treated.
  • Consider screening asymptomatic men with certain conditions that increase the risk of TD.
  • Exogenous TTh causes impairment of spermatogenesis.
  • There is no evidence that TTh causes prostate cancer.
  • Men on TTh require careful laboratory monitoring.
Read more Articles of the week

Video: Guideline of guidelines: testosterone therapy for testosterone deficiency

/by

Guideline of guidelines: testosterone therapy for testosterone deficiency

Read the full article

Abstract

We analysed the guidelines for testosterone therapy (TTh) produced by major international medical societies including: the American Urological Association, European Association of Urology, American Association of Clinical Endocrinologists, British Society for Sexual Medicine, Endocrine Society, International Society for Sexual Medicine, and the International Society for the Study of the Aging Male, and compared their recommendations.

All the organisations were in general agreement concerning the following key points:

  • Only men meeting the criteria for testosterone deficiency (TD) should be treated.
  • Consider screening asymptomatic men with certain conditions that increase the risk of TD.
  • Exogenous TTh causes impairment of spermatogenesis.
  • There is no evidence that TTh causes prostate cancer.
  • Men on TTh require careful laboratory monitoring.
View more videos

Editorial: Fusion‐guided biopsy to guide active surveillance in African‐American men?

/by

This timely and important article by Bloom et al. [1] highlights findings that warrant special attention in an effort to address and reduce racial disparities in low‐risk prostate cancer. At the population level, African‐American (AA) men are 76% more likely to be diagnosed with prostate cancer and 2.2‐times more likely to die from prostate cancer compared with other men in the USA. Emerging evidence suggests that racial disparities in patients diagnosed with advanced stage or higher‐risk disease may be predominantly accounted for by social factors and healthcare access [1,2]. In contrast, there is growing evidence that raises the question of whether disparities in low‐risk disease may be driven by underlying tumour and/or biopsy misclassification differences [2,3,4].

Bloom et al. [1] examined a USA study cohort from the National Cancer Institute (NCI) and found that amongst men referred to the NCI with a prior 12‐core systematic biopsy (SB), AA men with Gleason Grade (GG) 1 disease were nearly twice as likely to be upgraded by targeted multiparametric (mp)MRI fusion‐guided biopsy when compared with non‐AA men. These findings are consistent with contemporary data in the USA‐based Surveillance, Epidemiology and End Results Program, where amongst 20 125 men (including 2594 AA men) with clinical National Comprehensive Cancer Network (NCCN) low‐risk prostate cancer (GG 1 on biopsy) who underwent radical prostatectomy (RP) from 2010 to 2015, AA men were more likely to have pathological upgrading at the time of RP when compared with non‐AA men (47.3% vs 45.3%; adjusted hazard ratio 1.12, 95% CI 1.03–1.22, P = 0.007; unpublished analysis). Furthermore, the study findings are consistent with prior work that has shown that AA men with NCCN very‐low‐risk disease who underwent RP were more likely to have disease upgrading at RP (27.3% vs 14.4%; P < 0.001), positive surgical margins (9.8% vs 5.9%; P = 0.02), and higher Cancer of the Prostate Risk Assessment Post‐Surgical scoring system (CAPRA‐S) scores [5]; notably these AA men with very‐low‐risk disease also had a distinct zonal distribution of prostate cancer when compared with other men, with anterior tumours that are more difficult to sample by standard 12‐core SB alone [3].

Although low‐grade/risk disease is considered prognostically favourable and can be managed conservatively with active surveillance (AS), racial differences in outcome and zonal distribution of disease observed in favourable‐risk cohorts has led to controversy over the use of AS in AA men. Furthermore, conservative management trials have severely under‐represented patients of African descent. In this setting, most treatment guidelines advise caution when applying AS to AA patients. As such, although AS rates for low‐risk disease have nearly tripled in the USA from 14.5% to 42.1% from 2010 to 2015, there is lower relative uptake of AS for AA men compared with other men, even after adjusting for socioeconomic status, suggesting that providers and patients may be ‘risk‐stratifying’ AA patients with low‐risk disease into a higher‐risk category, and therefore less willing to proceed with AS [6].

Ultimately, the application of AS to AA patients with low‐risk disease will remain controversial and providers will make decisions based on observational data until a representative trial can help answer: (i) whether AA men diagnosed with low‐risk disease who are eligible for AS might be more likely to have distinct aggressive disease features compared with non‐AA men, and (ii) whether there might be strategies, such as guided‐fusion biopsy and/or incorporation of tumour genomics prior to AS, to help identify AA patients with underlying aggressive disease and appropriately select AA men with low‐risk disease for AS protocols.

The most interesting and important result found by Bloom et al. [1] is that amongst men who underwent mpMRI fusion‐guided biopsy after initial diagnosis of low‐risk disease on SB and who ultimately were continued on AS (those who were upgraded at the time of fusion‐guided biopsy became ineligible for AS), AA and non‐AA men had similar progression rates on AS. This result suggests that incorporation of techniques such as mpMRI and fusion biopsy may help better select AA men for AS when compared with standard 12‐core SB. Specifically, MRI guided‐biopsy may reduce disparate misclassification errors by increasing detection of higher grade and more anterior tumours that are more likely to be found in AA men who initially present with low‐risk disease after standard SB. As such, this strategy may represent one mechanism to better select AA men for AS and therefore may be able to reduce disparities in low‐risk disease.

The authors should be applauded for their important work, and this study builds on a growing body of evidence that clearly demonstrates the need for prospective trials examining different diagnostic/prognostic strategies that may reduce disparities in low‐risk disease by more appropriately selecting AA men for AS strategies.

by Brandon A. Mahal (@BrandonMahal)

References

  1. Krimphove MJ, Cole AP, Fletcher SA et al. Evaluation of the contribution of demographics, access to health care, treatment, and tumor characteristics to racial differences in survival of advanced prostate cancer. Prostate Cancer Prostatic Dis 2019; 22: 125– 36
  2. Mahal BA, Berman RA, Taplin ME, Huang FW Prostate cancer‐specific mortality across Gleason scores in black vs nonblack men. JAMA 2018; 320: 2479– 81
  3. Sundi D, Kryvenko ON, Carter HB, Ross AE, Epstein JI, Schaeffer EM Pathological examination of radical prostatectomy specimens in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in black American men. J Urol 2014; 191: 60– 7
  4. Mahal BA, Alshalalfa M, Spratt DE Prostate cancer genomic‐risk differences between African‐American and white men across Gleason scores. Eur Urol 2019; 75: 1038– 40
  5. Sundi D, Ross AE, Humphreys EB et al. African American men with very low‐risk prostate cancer exhibit adverse oncologic outcomes after radical prostatectomy: should active surveillance still be an option for them? J Clin Oncol 2013; 31: 2991– 7
  6. Butler S, Muralidhar V, Chavez J et al. Active surveillance for low‐risk prostate cancer in black patients. N Engl J Med 2019; 380: 2070– 2

 

 

Video: Use of mpMRI and fusion‐guided biopsies to properly select and follow African‐American men on active surveillance

/by

Use of multiparametric magnetic resonance imaging and fusion‐guided biopsies to properly select and follow African‐American men on active surveillance

Read the full article

Abstract

Objectives

To determine the rate of Gleason Grade Group (GGG) upgrading in African‐American (AA) men with a prior diagnosis of low‐grade prostate cancer (GGG 1 or GGG 2) on 12‐core systematic biopsy (SB) after multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB); and whether AA men who continued active surveillance (AS) after mpMRI and FB fared differently than a predominantly Caucasian (non‐AA) population.

Patients and methods

A database of men who had undergone mpMRI and FB was queried to determine rates of upgrading by FB amongst men deemed to be AS candidates based on SB prior to referral. After FB, Kaplan–Meier curves were generated for AA men and non‐AA men who then elected AS. The time to GGG upgrading and time continuing AS were compared using the log‐rank test.

Results

AA men referred with GGG 1 disease on previous SB were upgraded to GGG ≥3 by FB more often than non‐AA men, 22.2% vs 12.7% (P = 0.01). A total of 32 AA men and 258 non‐AA men then continued AS, with a median (interquartile range) follow‐up of 39.19 (24.24–56.41) months. The median time to progression was 59.7 and 60.5 months, respectively (P = 0.26). The median time continuing AS was 61.9 months and not reached, respectively (P = 0.80).

Conclusions

AA men were more likely to be upgraded from GGG 1 on SB to GGG ≥3 on initial FB; however, AA and non‐AA men on AS subsequently progressed at similar rates following mpMRI and FB. A greater tendency for SB to underestimate tumour grade in AA men may explain prior studies that have shown AA men to be at higher risk of progression during AS.

View more videos

 

Residents’ podcast: Artificial intelligence applications in urology

/by

Maria Uloko is a Urology Resident at the University of Minnesota Hospital. In this podcast she is joined by Dr Christopher Weight, an Associate Professor in the Department of Urology at the University of Minnesota. They are discussing a recent BJUI Article of the month:

Current status of artificial intelligence applications in urology and their potential to influence clinical practice

Read the full article

Abstract

Objective

To investigate the applications of artificial intelligence (AI) in diagnosis, treatment and outcome prediction in urologic diseases and evaluate its advantages over traditional models and methods.

Materials and methods

A literature search was performed after PROSPERO registration (CRD42018103701) and in compliance with Preferred Reported Items for Systematic Reviews and Meta‐Analyses (PRISMA) methods. Articles between 1994 and 2018 using the search terms “urology”, “artificial intelligence”, “machine learning” were included and categorized by the application of AI in urology. Review articles, editorial comments, articles with no full‐text access, and nonurologic studies were excluded.

Results

Initial search yielded 231 articles, but after excluding duplicates and following full‐text review and examination of article references, only 111 articles were included in the final analysis. AI applications in urology include: utilizing radiomic imaging or ultrasonic echo data to improve or automate cancer detection or outcome prediction, utilizing digitized tissue specimen images to automate detection of cancer on pathology slides, and combining patient clinical data, biomarkers, or gene expression to assist disease diagnosis or outcome prediction. Some studies employed AI to plan brachytherapy and radiation treatments while others used video-based or robotic automated performance metrics to objectively evaluate surgical skill. Compared to conventional statistical analysis, 71.8% of studies concluded that AI is superior in diagnosis and outcome prediction.

Conclusion

AI has been widely adopted in urology. Compared to conventional statistics AI approaches are more accurate in prediction and more explorative for analyzing large data cohorts. With an increasing library of patient data accessible to clinicians, AI may help facilitate evidence‐based and individualized patient care.

More podcasts

BJUI Podcasts now available on iTunes, subscribe here https://itunes.apple.com/gb/podcast/bju-international/id1309570262

 

Dr Weight specializes in the surgical treatment of urologic cancers including prostate, bladder, kidney, adrenal, testis and penile cancer. He performs open, endoscopic, laparoscopic, robotic (da Vinci) and retroperineoscopic surgery.

Dr Weight completed his residency training at Cleveland Clinic where he received several awards including the George and Grace Crile Traveling Fellowship Award, the Society of Laparoendoscopic Surgeons Resident Achievement Award and the ASCO Genitourinary Cancer Symposium Merit Award. Dr. Weight then completed a fellowship in Urologic Oncology at Mayo Clinic, where he also completed a Masters degree in Clinical and Translational Research from Mayo Graduate School and was awarded the Mayo Fellows Association Humanitarian Award.

Dr Weight believes that medical research is a key component to offering excellent patient care. His research is focused on improving patient outcomes and the use of artificial intelligence in different urologic applications. He is an author of more than 45 peer-reviewed publications and book chapters and has been invited to speak at regional, national and international conferences. 

© 2024 BJU International. All Rights Reserved.