Case studies: LUTS. Case 1 history. Case 1 - questions. Case 1 - outcome. Case 2 - history. Case 1 learning point 14/07/2015 DR JON REES

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Case 1 history Case studies: LUTS DR JON REES A 49 year old male comes to see you he has had gradual deterioration of his flow over the last few years- he saw a colleague of yours 6 weeks ago who recorded in the notes: Worsening stream last few years, long time to empty bladder. Nocturia x1. O/E no palp bladder; PR sl enlarged smooth prostate; Plan trial of alpha blocker. Rx Tamsulosin 400mcg od, review 1 month. Treatment has had no effect Case 1 - questions What has your colleague failed to do in his/her assessment & management that is recommended in the NICE LUTS in men guideline? What do you do now? Case 1 - outcome You decide to refer for specialist assessment The urologist fully examines the patient and finds a tight urethral meatal stenosis on examination. The patient undergoes surgical treatment with full resolution of his symptoms. Case 1 learning point Case 2 - history NICE recommends all men with LUTS have a focussed general examination, an examination of the external genitalia and digital rectal examination. Meatal stenosis or phimosis of the foreskin is a commonly missed cause of voiding symptoms. Treatment is by meatoplasty or circumcision not with alpha blockers... A 68 year old man presents following an episode of visible haematuria. He has no symptoms of a UTI but has had increasing LUTS (both storage & voiding) for the last 12 months. Non-smoker Otherwise fit & well 1

Case 2 examination & Case 2 specialist assessment Abdomen / external genitalia normal DRE large smooth prostate Urine dip blood +++, no leucocytes / nitrites MSU RBC++, no WBC, no growth egfr normal, no proteinuria, BP 140/80 Referred to haematuria clinic by 2 week wait Renal USS normal Flexible cystoscopy report: normal urethra, vascular occlusive prostate, bladder normal, no urothelial lesion. Discharged no other management plan in letter Case 2 - question Case 2 management & learning points He has a further episode of visible haematuria What should you do? He needs a CT Urogram to complete assessment of the upper tracts renal ultrasound can miss small renal tumours, small calculi, or urothelial tumours in the ureters. If this is normal, it is possible to use a 5-alpha reductase inhibitor both in the long term to control his LUTS and also in the short term to prevent further episodes of bleeding from his vascular prostate. Case 3 - history 39 year old male 6 month history of increased urgency, urinary frequency and nocturia x2. Good stream, no hesitancy or intermittency. Fit and well previously. Drinks 5-6 cups of tea / coffee per day plus a beer or glass of wine in the evening Case 3 examination & Abdomen normal External genitalia normal DRE small smooth prostate Urine dip NAD PSA / egfr not done Frequency volume chart shows marked daytime frequency with highly variable voided volumes between 50 and 300mls. Total daily urine output 2300mls. 2

Case 3 - questions What is your differential diagnosis? How would you manage this patient? Case 3 diagnosis & management Triad of frequency / urgency / nocturia = Overactive bladder syndrome (OAB) Initial management: lifestyle advice decrease intake of caffeinated / carbonated / alcoholic drinks: some improvement but still bothersome symptoms Referred to continence advisor for supervised bladder training including male pelvic floor exercises Consider treatment with an anti-cholinergic (e.g. Oxybutynin, tolterodine, solifenacin) if this fails Case 3 learning point Case 4 - presentation OAB is under-diagnosed in primary care many men presenting with storage symptoms are labelled with prostatism and unsuccessfully treated with alpha blockers etc. An understanding of the distinction between storage and voiding symptoms, taking a good history and use of a frequency volume chart, will all enable the primary care physician to make a correct diagnosis. 71 year old male presents with increasingly bothersome LUTS: he has both voiding (slow flow, hesitancy) and storage (frequency & nocturia) symptoms which have been gradually worsening for the last 2-3 years. He is otherwise fit he takes simvastatin 40mg (primary prevention) and is on blood pressure medication (not on diuretic) Case 4 examination & Abdomen normal External genitalia normal DRE large smooth prostate (unable to reach top of prostate with examining finger) Case 4 - questions What do you feel is the most likely diagnosis? According to the NICE LUTS guideline, how should this patient be managed? Urine dip NAD Frequency volume chart total daily voided volume approx 2l; increased daytime frequency, nocturia 1-3x per night. PSA 1.9 IPSS (recommended by NICE guideline as commencing medical therapy) 25 / 35 3

Case 4 - management He has moderate to severe bothersome LUTS with a large prostate (ie >30g) and a PSA>1.4 NICE LUTS guideline would therefore suggest consideration of combination therapy: Alpha blocker (e.g. Tamsulosin) plus 5-alpha reductase inhibitor (dutasteride / finasteride) Review patient at 4-6 weeks (to check efficacy of alpha blocker), 3-6 months (to check efficacy of 5ARI) then every 6-12months. Review is to assess symptoms, adverse effects of treatment, and effect of treatment on quality of life. Case 4 learning point NICE recommends consideration of combination therapy for men with moderate to severe LUTS (IPSS 8-19 = moderate, 20-35 = severe) who have a prostate estimated to be larger than 30g or a PSA > 1.4ng/ml. A prostate that feels large on examination, or where it is not possible to reach the upper pole with the examining finger is highly likely to be >30g. As well as being a tool for measuring prostate cancer risk, PSA is also a valuable indicator of the risk of progressive deterioration of LUTS / development if acute retention men with PSA > 1.4 are at highest risk. Case 5 - presentation 78 year old male presents with a 6-9 month history of mild LUTS, predominantly a slow intermittent flow with nocturia x3. He is otherwise fit and well, on no regular medication. Case 5- examination & Abdomen and external genitalia normal DRE large smooth prostate Urine dip NAD Frequency volume chart normal fluid ouput, nocturia 2-3x per night PSA discussed & offered result 8.6 ng/ml (age specific normal would be <4.0 ng/ml) Case 5 - questions Given this history, what is your main differential diagnosis? What would be recommended by the NICE LUTS guideline (& NICE referral for suspected cancer guideline)? Case 5 management Given raised PSA referred for specialist assessment Transrectal ultrasound 75cc (ie significantly enlarged prostate) Multiple prostate biopsies showed BPH only NICE guidance: LUTS with prostate >30g and/or PSA >1.4ng/ml i.e. at risk of progression offer a 5-alpha reductase inhibitor. PSA monitored in primary care noting that after 6 months on 5ARI result needs to be approximately doubled for comparison; patient reviewed at 6 months and annually thereafter. 4

Case 5 learning point In most men with LUTS, the decision to treat is based on the severity of symptoms and their impact on quality of life. Research has identified risk factors for progression i.e. Worsening symptoms, acute retention or surgery, and these include a large prostate, PSA>1.4, increasing age & increasing severity of symptoms. Despite this patients mild symptoms, given his age & PSA he is at risk and NICE would recommend use of a 5-alpha reductase inhibitor to lower this risk. Case 6 - presentation 76 year old male patient. Presented with LUTS to his GP 4 years ago assessed and commenced on alpha blocker (tamsulosin 400mcg once daily) with significant improvement in LUTS patient initially satisfied with result. Last 6-12 months has noticed a gradual return of his LUTS, flow slowing, more frequent during the day and getting up at night again Case 6 examination & Abdomen / external genitalia normal DRE large smooth prostate Case 6 - question What management options are available? Urine dip NAD PSA 1.7 IPSS 20 (had been 22 when commenced treatment, dropping to 13 when repeated 6 months after commencing tamsulosin) Case 6 management options 3 options presented to patient Persevere with symptoms as they are but significant risk they will continue to worsen (plus risk of urinary retention) Add 5ARI (dutasteride, finasteride) in combination with tamsulosin warning patient that this will take approximately 6 months before symptoms are noticeably improved, but this is optimal medical management with decreased risk of retention / surgery. Refer for surgical intervention Case 6 outcome Patient chooses trial of combination therapy (alpha blocker plus 5ARI) At 6 months patient pleased that symptoms have improved IPSS has decreased to 15 Symptoms and PSA monitored annually IPSS continues to improve for the following 12 months, dropping to 11 after 18 months of combination therapy 5

Case 6 learning points Research has shown that for patients with risk factors for progression use of an alpha blocker gives an initial significant improvement in symptoms but this improvement may not be sustained in the longer term i.e. beyond 3-4 years. These patients can either have a 5-alpha reductase inhibitor added when symptoms begin to deteriorate, or combination therapy can be used from the outset in higher risk patients to avoid this complication. Case 7 - history 59 year old male presents having just completed treatment for his third urinary tract infection in 6 months. He has noticed gradually progressive lower urinary tract symptoms over the last 12-18 months his flow has slowed and he has hesitancy. He is passing urine twice at night and more frequently during the day he also describes that he feels he is not completely emptying his bladder. He has occasional episodes of nocturnal enuresis. Case 7 examination Abdominal examination you suspect he is dull to percussion above his pubic symphysis to just below the umbilicus. Case 7 - question What s would you carry out (as recommended by NICE LUTS guideline)? External genitalia are normal. Digital rectal examination large smooth prostate. Case 7 - Investigations recommended by NICE: Urine dip NAD Serum creatinine / egfr normal PSA (n.b. do not measure PSA for at least 4-6weeks after UTI as may give false positive result) 1.1 Referred for specialist assessment given recurrent UTI with LUTS and possible chronic retention Case 7 specialist assessment Urine flows slow flow rate (Qmax 13ml/sec Post micturition residual (on ultrasound) 1050mls. Normal kidneys on ultrasound no hydronephrosis Patient undergoes urgent TURP given moderate symptoms, no hydronephrosis and stable renal function he is not catheterised preoperatively 6

Case 7 learning points Always examine the abdomen for a palpable / percussable bladder. Nocturnal enuresis is a red flag symptom which should raise suspicion of chronic retention. NICE recommends all patients with chronic retention have a serum creatinine and renal ultrasound if impaired renal function or hydronephrosis they should be catheterised prior to surgery. If renal function and ultrasound normal then can proceed to surgery without prior catheterisation. Intermittent self-catheterisation is an option for patients prior to surgery or for those in whom surgery is inappropriate. Case 8 - history A 76 year old man comes to see you. He has been taking combination therapy (combined alpha blocker and 5-alpha reductase inhibitor) for the last 3 years for LUTS secondary to BPH. His LUTS are well controlled on treatment. His PSA prior to treatment was 2.1, but this dropped to 0.8 after 6 months on treatment. Over the last 6 months his PSA has increased from 0.9 to 2.4 this needs to be doubled as he has been on 5ARI for >6 months. (n.b. agespecific normal range <5.0 for a man >70years old). Case 8 - question His PSA remains in normal range what would you do now? Case 8 - outcome You examine his prostate but dot detect anything worrying on DRE. Given the rise in his PSA you refer for a specialist opinion. The urologist notes a slightly firm left lobe and carries out a TRUS and biopsy of the prostate. A Gleason 8 i.e. Moderately aggressive prostate cancer is diagnosed and he is treated with radical radiotherapy. Case 8 learning point Prostate cancer can be present in a patient with a normal PSA. PSA results for men on 5-alpha reductase inhibitors (treated for >6 months) need to be doubled to compare with age-specific ranges. PSA will slowly rise in men with BPH, but generally at a velocity of less than 0.5 or 0.75 ng/ml per year. This patient had a rise of 1.5ng/ml in 6 months which is highly suspicious, despite remaining within the age-specific range. Case 9 - history An 80-year old male presents in great distress he has been unable to pass urine all day and is now in pain. He has had gradually deteriorating LUTS for the last few years but has not discussed this as he felt it was normal for an ageing male. He has a palpable bladder and a large smooth prostate on DRE 7

Case 9 - questions What are your options? Case 9 - outcome He needs immediate catheterisation What is recommended in the NICE LUTS guideline? This can either be performed in the community or he will need emergency hospital admission. If catheterised in the community he can be offered a trial without catheter (TWOC) in approximately 2 weeks NICE recommends he is commenced on an alpha-blocker prior to TWOC. Following removal of catheter he will need to continue his alpha blocker and a full assessment made to determine optimal ongoing medical management e.g. combination therapy. Case 9 learning point Acute retention of urine is a highly distressing condition for patients. Studies suggest increased all-cause mortality in men who experience acute retention: in the 75-84 year age band a one-year mortality rate of almost 30% in men with co-morbidities. Optimal medical management including risk stratification and therapy targetted at those most at risk of retention can decrease rates of retention, the high costs associated with treatment and the subsequent increased mortality rates. Case 10 - history A 60 year old man presents with progressive deterioration of LUTS over the last 6-12 months. His symptoms are causing significant bother and he is keen to embark on and treatment. When examining him you find you are unable to reach his prostate on digital rectal examination. Case 10 - question How can you assess his prostate fully if you are unable to feel it on DRE? Case 10 management & learning point You have 2 priorities firstly to assess for the risk of prostate cancer, and secondly to determine prostate size to help guide treatment for BPH. PSA can be used for both these purposes it s well understood role is for prostate cancer screening. PSA is also a surrogate marker for prostate volume and risk of progressive symptoms a PSA >1.4ng/ml correlates with a prostate volume of >30cc (i.e. significantly enlarged) and is the strongest risk factor for clinical progression in BPH. 8