Treatment of Invasive Bladder Cancer in the Elderly and Frail Pa9ent

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1 Treatment of Invasive Bladder Cancer in the Elderly and Frail Pa9ent Jehonathan H Pinthus MD, Ph.D, FRCSC Associate Professor Department of Surgery/Urology McMaster University

2 Life expectancy Current age male female

3 The probability of developing invasive bladder cancer increases with age Median age of diagnosis in USA is 73 years old Galsky MD Journal of Geriatric Oncology 2015 American Cancer Society Facts & Figures 2008

4 Referral palern to the JCC mul9- disciplinary bladder cancer clinic Octogenerians & nanogenerians 36% < >90 Mean age: 75 years Median age: 76 years Range: years

5 Poten9al explana9ons More aggressive superficial disease Delay in diagnosis Biology?

Superficial UC is more aggressive in elderly pa9ents Kohjimoto et al 2010 491 pahents treated with TUR- BT +/- intravesical BCG Larger, mulhfocal and high grade tumours were more frequent with

6 Superficial UC is more aggressive in elderly pa9ents Kohjimoto et al pahents treated with TUR- BT +/- intravesical BCG Larger, mulhfocal and high grade tumours were more frequent with increasing age Intra- vesical BCG was less frequently used in elderly pahents Age was an independent risk factor tumour recurrence and progression Recurrence was 2.3 Hmes in pahents >80yr compared to pahents<69 years

8 Delay in diagnosis SEER data base of 29,740 pahents who had hematuria in the year before a bladder cancer diagnosis ( ) Hollenbeck et al Cancer 2010

9 Show me the results of the urine culture!

10 Older pa9ents tend to receive less cura9ve treatment for MIBC An analysis of 3262 Medicare beneficiaries age 65 years or older with MIBC from the Surveillance, Epidemiology, and End Results Medicare (SEER) data Only 21% of MIBC pa9ents older than 65 years received RC (overall survival was beler in these pa9ents)

11 Half of the pa9ents older than 85 received no treatment

12 Natural history of MIBC Le\ untreated, most pahents with MIBC suffer significant morbidity and die of the disease within 2 years of the diagnosis. A life expectancy of 2 years has been suggested to consider radical cystectomy * Skinner Urol Oncol 2007

13 Life expectancy Current age male female

14 The percep9on: Elderly pa9ents will not tolerate RC and urinary diversion because of age, frailty and co- morbidi9es

16 Func9onal age dose not equal chronological age: Use specific opera9ve risk assessment tools

17 PACE: PereoperaHve Assessment of Cancer in Elderly Associate with 30 day morbidity

18 Behind the risk assessment: Balance the discussion: specify the benefit of the surgery in terms of oncological outcome (OS and CSS) but discuss effects on QOL. Is there an effec9ve caregiver? An effechve caregiver can prevent the transformahon of disability into handicap.

19 SEER database ( ) of 13,796 pahents who were diagnosed with bladder cancer (24% octogenerians). Ex9rpa9ve surgery had the lowest HR of any other treatment strategies for both bladder cancer- specific and all- cause mortality Hollenbeck Urology 2004

20 SEER data 10,807 consecuhve pahents with muscle invasive UC pahents underwent RC and 2773 had bladder preservahon (had to include RT) Exclusion: no data on stage, grade, primary Tx or cases with ptis, pt1, ptx

21 Overall survival

22 Cancer specific survival Pa9ents who had RC had beler CSS regardless of age (15 months advantage or 52 months if N+ cases are excluded for octagenerians)

23 Author design Elderly Defini9on Mendiola (2007) Hollenbeck (2004) Clark (2005) Yamanaka (2007) # of pa9ents Overall survival CSS Case series >80y 49 36%- 5y 44%- 5y RetrospecHve Cohort Case series <60y 60-69y 70-79y >80y >80y 369/3354 RC- 50% Rads- 30% TURBT 25% palliahve 5% Case series >80y 72/629 Not reported RC- 76% Rads- 52% TURBT 52% Notes 2 years survival data 50/ %- 5y 45%- 5y Old pahents had worse stage and didn t receive adjuvant chemo 40%- 5y Old pahents had worse stage. Controlling for stage: Same CSS

24 Octagenerians undergoing RC have higher pathological stage and are less likely to be treated with neo/adj chemotharapy 50/1054 were octagenerians Clark et al 2005

25 RC for MIBC in the Octogenerians Associates with the highest survival rates as compared to other treatment strategies pt is typically more advanced Is it safe?

$50%) or major (17% vs. 13%) complicahons even a\er adjustment to baseline characterishcs.$

26 Retrospec9ve review of complica9ons following RC (n=1,142) at MSKCC (n=117) No significant rate of minor (55% vs. 50%) or major (17% vs. 13%) complicahons even a\er adjustment to baseline characterishcs. But, higher overall 90- d mortality rate (6.8% vs. 2.2%)

27 Morbidity and complica9ons Most studies report that RC is safe in octagenerians Overall mortality rate 4% (However, one needs to consider 90- day mortality rates which have been reported to be as high as 10% in pahents >80 year old Nielsen et al BJU Int 2014) But- All are retrospechve (highly) selected populahon Froehner et al Eur Urol 2009

28 In principal: Death caused by undertreated cancer is much more common than is death related to inter- current medical diseases, and the quality of life during survival Hme is strongly affected

29 Alterna9ve treatment op9ons TURBT only Bladder sparing ERBT Diversion

30 TURBT only 133 pahents with more than 15 year follow- up Exclusion: ct3 Nodular tumours> 3cm Hydronephrosis Adenopathy MulH- focal disease and CIS included

31 TURBT only- data from >15 year follow- up Condi9onal to: 1. NegaHve biopsies (n=5) of the tumour bed post complete TUR- BT 2. Tumour size<3cm

32 Par9al cystectomy Minority are eligible (<10%): No CIS, no mulh- focality, tumour locahon, adequate bladder capacity No data in elderly In highly selected cases: 5 year overall, CSS and recurrence free survivals are 67%, 87% and 39%.* *Kassouf J Urol 2006

33 Bladder sparing In very selected populahon 5 y survival 50-60% but 40% will loose their bladder (Kaufman Lancet 2009) Eligibility? Oncological Chemo Radia9on Salvage RC High proporhon are Locally advanced Ability to tolerate* Side effects Very risky If your pa9ent can not tolerate RC what are the the odds that he can tolerate cispla9ne based chemotherapy? Only 60% of elderly patents are candidates for cisplatne based therapy defined by Cr clearance of >/= 60 ml/min (Dash et al Cancer 2006)

34 RadiaHon plus concurrent 5- fluorouracil and mitomycin C GFR> 25ml/min Loco regional disease control was beqer compared to radiahon alone 2 years salvage RC rate 11.4% 5 years OS was 48% for the chemo radiahon arm

35 Take home massages MIBC is common in octagenerians Special aqenhon should be paid for early detechon Recurrence and progression of NMIBC are more common in octagenerians Compared to other treatments, radical cystecomy results in the best oncological outcome in octagenerians with MIBC

36 Take home massages Risk of complica9on of RC in the elderly is mainly influenced by medical condi9on rather than chronological age Radical cystectomy can be done safely in octagenerians- Assemble a support team (cardiologist, ICU, geriatrician, nutrihonist, occupahonal therapist, social worker) The op9on of radical cystectomy should not be withheld from appropriately selected octagenerians Ul9mately, once you conveyed all info, respect the pa9ent perspec9ves- She/he are older than you..

Management options for high-risk, BCG-refractory NMIBC. Alan M. Nieder, M.D. Columbia University Division of Urology Mount Sinai Medical Center

$Management options for high-risk, BCG-refractory NMIBC. Alan M. Nieder, M.D. Columbia University Division of Urology Mount Sinai Medical Center$ Management options for high-risk, BCG-refractory NMIBC Alan M. Nieder, M.D. Columbia University Division of Urology Mount Sinai Medical Center Bladder Cancer in U.S. 4 th most common cancer in men 9 th