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Article of the Week: Profiling microRNA from nephrectomy and biopsy specimens

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.

Profiling microRNA from nephrectomy and biopsy specimens: predictors of progression and survival in clear cell renal cell carcinoma

 

Casey G. Kowalik*, Drew A. Palmer*, Travis B. Sullivan, Patrick A. TeebagyJohn M. Dugan, John A. Libertino*, Eric J. Burks, David Canes* and Kimberly M. Rieger-Christ

 

Departments of *Urology, Translational Research Ian C. Summerhayes Cell and Molecular Biology Laboratory, and Pathology, Lahey Hospital and Medical Center, Burlington, MA, USA

 

Abstract

Objective

To identify microRNA (miRNA) characteristic of metastatic clear cell renal cell carcinoma (ccRCC) and those indicative of cancer-specific survival (CSS) in nephrectomy and biopsy specimens. We also sought to determine if a miRNA panel could differentiate benign from ccRCC tissue.

Materials and Methods

RNA was isolated from nephrectomy and kidney biopsy specimens (n = 156 and n = 46, respectively). Samples were grouped: benign, non-progressive, and progressive ccRCC. MiRNAs were profiled by microarray and validated by quantitative reverse transcription-polymerase chain reaction. Biomarker signatures were developed to predict cancer status in nephrectomy and biopsy specimens. CSS was examined using Kaplan–Meier and Cox proportional hazards analyses.

Results

Microarray analysis revealed 20 differentially expressed miRNAs comparing non-progressive with progressive tumours. A biomarker signature validated in nephrectomy specimens had a sensitivity of 86.7% and a specificity of 92.9% for differentiating benign and ccRCC specimens. A second signature differentiated non-progressive vs progressive ccRCC with a sensitivity of 93.8% and a specificity of 83.3%. These biomarkers also discriminated cancer status in biopsy specimens. Levels of miR-10a-5p, -10b-5p, and -223-3p were associated with CSS.

Conclusion

This study identified miRNAs differentially expressed in ccRCC samples; as well as those correlating with CSS. Biomarkers identified in this study have the potential to identify patients who are likely to have progressive ccRCC, and although preliminary, these results may aid in differentiating aggressive and indolent ccRCC based on biopsy specimens.

Editorial: The utility of microRNAs as biomarkers in predicting progression and survival in patients with clear-cell renal cell carcinoma

RCC constitutes a diverse group of malignancies, yet the clear-cell subtype comprises ~80% of all diagnosed RCC cases [1]. The widespread use of abdominal imaging and subsequent stage migration has resulted in improved RCC 5-year cancer-specific survival. However, the overall mortality of RCC remains largely unchanged [2] and one-third of the patients have metastatic disease at the time of presentation [3]. Accordingly, the ability to precisely predict patient outcome has become an increasingly significant question in the management of these patients with RCC.

Accruing evidence suggests that changes in various biomarkers and their consequent downstream pathways affect cancer initiation and progression. Therefore, accurate prediction of the outcome and prognosis after treatment is necessary [4]. MicroRNAs (miRNAs) are small non-coding RNA molecules that can have significant functions in tumorigenesis [5]. Because of their ability in post-transcriptional regulation of gene expression, tumour-specific genetic defects in miRNA biogenesis and production correlate with development of human cancers. Thus, the differential expression of specific miRNA signatures in different tumours might become an important tool to help in directing cancer diagnosis and treatment [5].

As such, Kowalik et al. [6] report on profiling miRNA to identify biomarker signatures predictive of clear-cell RCC (ccRCC) progression and survival. The authors used 202 formalin-fixed paraffin-embedded samples to isolate RNA from nephrectomy and biopsy specimens (n = 156 and n = 46, respectively) (Fig. 1).

Figure 1. Schematic diagram of miRNA-based biomarkers and potential utility in clinical decision-making approach for targeted therapy and RCC personalised treatment.

The primary analysis of their study [6] focused on the identification of miRNA signatures capable of differentiating between benign and ccRCC, as well as discerning those patients with a non-progressive ccRCC from a progressive clear-cell subtype. The secondary outcome examined the association of miRNA profiles discovered on cancer-specific survival.

In their initial microarray screening 20 differentially expressed miRNAs, comparing non-progressive with progressive tumours, were identified. The authors found four miRNA panels (10a-5p, 10b-5p, 106a-5p, and 142-5p) as a potential biomarker signature. This model was validated in nephrectomy specimens and resulted in a sensitivity of 86.7%, a specificity of 92.9%, and an area under the curve (AUC) of 0.930 for detecting ccRCC. Further analysis revealed a second signature of two biomarkers (miR-10a-5p and -223-3p) with 93.8% sensitivity, 83.3% specificity, and an AUC of 0.932 when validated for detecting progressive ccRCC. Similarly, the differential expression of these biomarkers could delineate cancer status in biopsy specimens. For correlation of miRNA expression levels with cancer-specific survival, higher expression levels of (miR-10a-5p and miR-10b-5p) and a lower expression level of (miR-223-3p) were significantly associated with survival (P< 0.001), and the median survival times were not reached.

In conclusion, the lack of precise prediction tools has led the authors to explore the potential utility of miRNAs as biomarkers to detect disease presence, biological aggressiveness, and prognosis in ccRCC. However, until future multicentre large prospective studies validate the results of the present work, the transition of miRNA from bench to bedside is emerging on the horizon and has encouraged urologists and scientists to pursue intense translational research in the field. The ability to use miRNAs as biomarkers might be promising for diagnostic and prognostic purposes. These biomarkers may exemplify different aspects of RCC pathogenesis and may potentially have important therapeutic implications to help in a clinical decision-making approach for targeted therapy and RCC personalised treatment.

Firas G. Petrosand Christopher J.D. Wallis†‡
*Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USADivision of Urology, Department of Surgery, University of Toronto, Toronto, ON, Canada and Division of Urology, Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

 

 

References

 

1 Reuter VE, Presti JC Jr. Contemporary approach to the classication of renal epithelial tumors. Semin Oncol 2000; 27: 12437

 

2 Hollingsworth JM, Miller DC, Daignault S, Hollenbeck BK. Rising incidence of small renal masses: a need to reassess treatment effect. J Natl Cancer Inst 2006; 98: 13314

 

3 Gupta K, Miller JD , Li JZ, Russell MW, Charbonneau C. Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): literature review. Cancer Treat Rev 2008; 34: 193205

 

 

5 Esquela-Kerscher A, Slack FJ. Oncomirs microRNAs with a role in cancer. Nat Rev Cancer 2006; 6: 25969

 

 

Article of the Week: Impact of Re-TUR on BCG-Treated T1 HG/G3 Bladder Cancer

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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Francesca Pisano and Paolo Gontero, discussing their paper.

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

The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette–Guerin

Paolo Gontero1, Richard Sylvester2, Francesca Pisano1, Steven Joniau3, Marco Oderda1, Vincenzo Serretta4,Stephane Larre5, Savino Di Stasi6, Bas Van Rhijn7, Alfred J.Witjes8, Anne J. Grotenhuis8, Renzo Colombo9, Alberto Briganti9, Marek Babjuk10, Viktor Soukup10, Per-Uno Malmstrom11, Jacques Irani12, Nuria Malats13, Jack Baniel14, RoyMano14, Tommaso Cai15, Eugene K. Cha16, Peter Ardelt17, John Vakarakis18, Riccardo Bartoletti19, Guido Dalbagni20, Shahrokh F. Shariat16, Evanguelos Xylinas16, Robert J.Karnes21 and Joan Palou22

 

1Urology Clinic, Citta della Salute e della Scienza di Torino, University of Studies of Turin, Turin ,4Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, 6Policlinico Tor Vergata-University of Rome, Rome, 9Dipartimento di Urologia, Universita Vita-Salute. Ospedale S. Raffaele, Milan, 15Department of Urology, SantaChiara Hospital, Trento, 19Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, 2Formerly Department of Biostatistics, EORTC Headquarters, Brussels, 3Oncologic and Reconstructive Urology, Department of Urology, University Hospitals Leuven, Leuven, Belgium, 5Department of Surgical Science, John Radcliffe Hospital, University of Oxford, Oxford, UK, 7Department of Urology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, 8Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 10Department of Urology, Motol Hospital, University of Praha, Praha, Czech Republic, 11Department of Urology, Academic Hospital, Uppsala University, Uppsala, Sweden, 12Department of Urology, Centre Hospitalier Universitaire La Miletrie, University of Poitiers, Poitiers, France, 13Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, 22Department of Urology, Fundacio Puigvert, University of Barcelona, Barcelona, Spain, 14Department of Urology, Rabin Medical Centre, Tel Aviv, Israel, 16Department of Urology, Weill Medical College of Cornell University in New York City, 20Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY, 21Department of Urology, Mayo Clinic, Rochester, MN, USA, 17Facharzt fur Urologie, Abteilung fur Urologie. Chirurgische Universitats klinik, Freiburg, Germany, and 18Department of Urology, Sismanoglio Hospital, University of Athens, Athens, Greece

 

Read the full article

Objectives

To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS).

Patients and methods

In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette–Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups.

JUlAOTW4Results

Results

Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints.

Conclusions

Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.

Editorial: Time to re-evaluate and refine re-TUR in bladder cancer?

In this issue of BJUI, Gontero et al. [1] present data from a large multi-centre study that should allow us to re-evaluate and refine the indications for re-transurethral resection (TUR) in bladder cancer.

Herr [2] first described this procedure in 1999 and for the past 16 years the indications have remained largely unchanged and are summarised in the latest European Association of Urology guidelines on non-muscle-invasive bladder cancer (NMIBC) [3]:

  • After incomplete initial TUR of bladder tumour (TURBT).
  • If there is no muscle in the specimen after initial resection.
  • In all T1 tumours.
  • In all Grade 3 tumours except primary carcinoma in situ.

In a multi-centre retrospective study of 2 451 patients with high-grade (HG)/Grade 3 (G3) T1 NMIBC treated with BCG, Gontero et al. [1]examined 935 patients who had re-TUR (38% of the total, itself a low figure). Patients were divided into four groups according to the presence or absence of detrusor muscle in the first TURBT specimen:

  • No muscle, no re-TUR
  • No muscle, re-TUR
  • Muscle, no re-TUR
  • Muscle, re-TUR

The authors found that re-TUR only had a positive impact on recurrence, progression, cancer-specific and overall survival, if detrusor muscle was not present in the original specimen. Importantly, in the presence of detrusor muscle in the original specimen, re-TUR did not improve outcomes. The authors conclude that re-TUR may be unnecessary in HG/G3 T1 patients if detrusor muscle is present at the first TURBT.

These findings are important for two reasons: firstly, Herr’s [2] paper was the first to draw attention to the finding that TURBT, a routine urological procedure, was often carried out inadequately. In recent years, the importance of carrying out a high-quality TURBT has been increasingly recognised [4], whilst the presence of detrusor muscle in the TURBT specimen has been shown to be a good measure of the technical quality of a TURBT [5]. This paper [1] further reinforces the importance of obtaining detrusor muscle in the first TURBT. Indeed, as failure to do so results in the patient having to have a second operation and delays their treatment, perhaps we should start to think of a failure to obtain detrusor muscle at the first TURBT in much the same way as positive margin rates are used as a measure of the quality of radical prostatectomy and by inference, the skill of the surgeon.

Secondly, re-TUR arguably serves one overarching purpose: to identify patients with muscle-invasive bladder cancer (MIBC) who have been under-staged by an inadequate first TURBT and who without a re-TUR would be inadequately treated.

Although a secondary role of re-TUR is to identify patients with residual NMIBC, which has some prognostic value, in practice it rarely changes the patient’s management in this setting, which is intravesical therapy usually with BCG. However, in many healthcare systems the timely organisation of a re-TUR within the recommended 6 weeks is challenging and there is usually a further delay of at least 2 weeks until the pathology is reviewed and a patient with NMIBC can finally commence treatment. In this context, it is not surprising that a recent paper in BJUI showed that the interval to re-TUR was a predictor of recurrence and progression and that a re-TUR after 7 weeks was associated with a much worse outcome [6]. It therefore seems logical to reserve re-TUR only for those patients who truly need it, so that limited resources are focused on ensuring that they receive their operation in a timely manner, ideally within 2–4 weeks. If adopted into day-to-day urological practice, the findings by Gontero et al. [1] will allow many patients with HG/G3 T1 and detrusor muscle in the first TURBT specimen to avoid a re-TUR and start intravesical therapy without further delay. Pragmatically, the same should apply to patients with HG/G3 Ta with detrusor muscle in the specimen. On the other hand, HG/G3 T1 patients without detrusor muscle should be fast-tracked for re-TUR as soon as is practicable and certainly no later than 6 weeks.

The article [1] does have some shortcomings. The study design excludes patients with MIBC, so we do not know by comparison how many patients with MIBC were under-staged at the initial TUR based on subsequent re-TUR but as the authors point out, their conclusions would hold true even in this group, as it is very unlikely that one would miss MIBC if there was adequate detrusor muscle in the pathology specimen.

In conclusion, we should consider refining the indications for re-TUR to improve the utilisation of healthcare resources and ensure that for those that need it, a re-TUR is carried promptly whilst for those that do not, essential intravesical treatment is not delayed.

Read the full article
A. Hugh Mostad, Consultant Urologist and Honorary
Senior Lecturer The Royal Surrey County Hospital, Guildford, Surrey, UK

 

References

 

Video: Impact of Re-TUR on BCG-Treated T1 HG/G3 Bladder Cancer

The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette–Guerin

Paolo Gontero1, Richard Sylvester2, Francesca Pisano1, Steven Joniau3, Marco Oderda1, Vincenzo Serretta4,Stephane Larre5, Savino Di Stasi6, Bas Van Rhijn7, Alfred J.Witjes8, Anne J. Grotenhuis8, Renzo Colombo9, Alberto Briganti9, Marek Babjuk10, Viktor Soukup10, Per-Uno Malmstrom11, Jacques Irani12, Nuria Malats13, Jack Baniel14, RoyMano14, Tommaso Cai15, Eugene K. Cha16, Peter Ardelt17, John Vakarakis18, Riccardo Bartoletti19, Guido Dalbagni20, Shahrokh F. Shariat16, Evanguelos Xylinas16, Robert J.Karnes21 and Joan Palou22

 

1Urology Clinic, Citta della Salute e della Scienza di Torino, University of Studies of Turin, Turin ,4Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, 6Policlinico Tor Vergata-University of Rome, Rome, 9Dipartimento di Urologia, Universita Vita-Salute. Ospedale S. Raffaele, Milan, 15Department of Urology, SantaChiara Hospital, Trento, 19Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, 2Formerly Department of Biostatistics, EORTC Headquarters, Brussels, 3Oncologic and Reconstructive Urology, Department of Urology, University Hospitals Leuven, Leuven, Belgium, 5Department of Surgical Science, John Radcliffe Hospital, University of Oxford, Oxford, UK, 7Department of Urology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, 8Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 10Department of Urology, Motol Hospital, University of Praha, Praha, Czech Republic, 11Department of Urology, Academic Hospital, Uppsala University, Uppsala, Sweden, 12Department of Urology, Centre Hospitalier Universitaire La Miletrie, University of Poitiers, Poitiers, France, 13Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, 22Department of Urology, Fundacio Puigvert, University of Barcelona, Barcelona, Spain, 14Department of Urology, Rabin Medical Centre, Tel Aviv, Israel, 16Department of Urology, Weill Medical College of Cornell University in New York City, 20Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY, 21Department of Urology, Mayo Clinic, Rochester, MN, USA, 17Facharzt fur Urologie, Abteilung fur Urologie. Chirurgische Universitats klinik, Freiburg, Germany, and 18Department of Urology, Sismanoglio Hospital, University of Athens, Athens, Greece

 

Read the full article

Objectives

To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS).

Patients and methods

In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette–Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups.

JUlAOTW4Results

Results

Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints.

Conclusions

Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.

Article of the Month: Progression and treatment of incident lower urinary tract symptoms (LUTS) among men in the California Men’s Health Study

Every week the Editor-in-Chief selects the 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.

This week we feature a video from Dr. Steven Jacobsen discussing his paper. 

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

Progression and treatment of incident lower urinary tract symptoms (LUTS) among men in the California Men’s Health Study

Lauren P. Wallner, Jeff M. Slezak*, Ronald K. Loo†, Virginia P. Quinn*, Stephen K. Van Den Eeden‡ and Steven J. Jacobsen*

Department of Medicine and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, *Department of Research and Evaluation, Kaiser Permanente Southern California, †Department of Urology, Southern California Permanente Medical Group, Pasadena, CA, and ‡Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

Read the full article
OBJECTIVES

To characterise the progression and treatment of lower urinary tract symptoms (LUTS) among men aged 45–69 years in the California Men’s Health Study.

PATIENTS AND METHODS

A total of 39 222 men, aged 45–69 years, enrolled in the Southern California Kaiser Permanente Health Plan were surveyed in 2002–2003 and again in 2006–2007. Those men who completed both surveys who did not have a diagnosis of benign prostatic hyperplasia (BPH) and were not on medication for LUTS at baseline were included in the study (N = 19 505). Among the men with no or mild symptoms at baseline, the incidence of moderate/severe LUTS (American Urological Association Symptom Index [AUASI] score ≥8) and odds of progression to severe LUTS (AUASI score ≥20) was estimated during 4 years of follow-up.

RESULTS

Of the 9640 men who reported no/mild LUTS at baseline, 3993 (41%) reported moderate/severe symptoms at follow-up and experienced a 4-point change in AUASI score on average. Of these men, 351 (8.8%) had received a pharmacological treatment, eight (0.2%) had undergone a minimally invasive or surgical procedure and 3634 (91.0%) had no treatment recorded. Men who progressed to severe symptoms (AUASI score ≥20; n = 165) were more likely to be on medication for BPH (odds ratio [OR] 8.09, 95% confidence interval [CI] 5.77–11.35), have a BPH diagnosis (OR 4.74, 95% CI 3.40–6.61) or have seen a urologist (OR 2.49, 95% CI 1.81–3.43) when compared with men who did not progress to severe symptoms (AUASI score <20).

CONCLUSION

These data show that the majority of men who experienced progression did not have pharmacological or surgical therapy for their symptoms and, therefore, may prove to be good candidates for a self-management plan.

Video: Progression and treatment of incident lower urinary tract symptoms (LUTS) among men in the California Men’s Health Study

Progression and treatment of incident lower urinary tract symptoms (LUTS) among men in the California Men’s Health Study

Lauren P. Wallner, Jeff M. Slezak*, Ronald K. Loo†, Virginia P. Quinn*, Stephen K. Van Den Eeden‡ and Steven J. Jacobsen*

Department of Medicine and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, *Department of Research and Evaluation, Kaiser Permanente Southern California, †Department of Urology, Southern California Permanente Medical Group, Pasadena, CA, and ‡Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

Read the full article

OBJECTIVES

To characterise the progression and treatment of lower urinary tract symptoms (LUTS) among men aged 45–69 years in the California Men’s Health Study.

PATIENTS AND METHODS

A total of 39 222 men, aged 45–69 years, enrolled in the Southern California Kaiser Permanente Health Plan were surveyed in 2002–2003 and again in 2006–2007. Those men who completed both surveys who did not have a diagnosis of benign prostatic hyperplasia (BPH) and were not on medication for LUTS at baseline were included in the study (N = 19 505). Among the men with no or mild symptoms at baseline, the incidence of moderate/severe LUTS (American Urological Association Symptom Index [AUASI] score ≥8) and odds of progression to severe LUTS (AUASI score ≥20) was estimated during 4 years of follow-up.

RESULTS

Of the 9640 men who reported no/mild LUTS at baseline, 3993 (41%) reported moderate/severe symptoms at follow-up and experienced a 4-point change in AUASI score on average. Of these men, 351 (8.8%) had received a pharmacological treatment, eight (0.2%) had undergone a minimally invasive or surgical procedure and 3634 (91.0%) had no treatment recorded. Men who progressed to severe symptoms (AUASI score ≥20; n = 165) were more likely to be on medication for BPH (odds ratio [OR] 8.09, 95% confidence interval [CI] 5.77–11.35), have a BPH diagnosis (OR 4.74, 95% CI 3.40–6.61) or have seen a urologist (OR 2.49, 95% CI 1.81–3.43) when compared with men who did not progress to severe symptoms (AUASI score <20).

CONCLUSION

These data show that the majority of men who experienced progression did not have pharmacological or surgical therapy for their symptoms and, therefore, may prove to be good candidates for a self-management plan.

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