Urinary Bladder, Irrational Fear of Peeing in Public, Bladder Shy, Shy Bladder Help, Public Phobia
Optimal sequencing in treatment muscle invasive bladder ... · • About a third (36%) died with...
Transcript of Optimal sequencing in treatment muscle invasive bladder ... · • About a third (36%) died with...
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Optimal sequencing in treatment muscle invasive bladder cancer
: oncologists
Phichai Chansriwong, MD
Ramathibodi Hospital, Mahidol University
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Slide 2
Presented By Andrea Apolo at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Slide 18
Presented By Jeffrey Holzbeierlein at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Cystectomy Alone
• “Standard of care” approach (with PLND)
• Disadvantages include:- loss of organ function
• 50% recurrence rate with-in 2 years
• Broadly--5-year survival rates:-• pT2:60-80%;
• pT4:0-20%;
• Unsuspected N1:60%
• N2/3 : 0-23%
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Compare and Contrast
Neoadjuvant
• Deals with micromets sooner
• Best evidence of benefit
• Concern re: delay in surgery
• ? Increased surgical complications
• Is benefit worth it?
Adjuvant
• Treats only the highest risk pts.
• No delay in local Rx
• Evidence of benefit is weaker
• Delays in healing may preclude giving therapy
• Is benefit worth it?
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NEOADJUVANT CHEMOTHERAPY
THE JOURNAL OF UROLOGY, Vol. 177, 437-443, February 2007
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Neoadjuvant Chemotherapy
• MRC and EORTC May 2002 : MCV
• MTX(30 mg/m2 d 1),
• vinblastine (4 mg/m2 d 1)
• cisplatin (100 mg/m2 d 2).
• T2-4a n0-x m0 TCC
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MRC and EORTC Neoadjuvant Chemotherapy• OS was superior chemotherapy
• at 3 years (55% vs. 50%),
• 5 years (50% vs. 44%),
• and 8 years (43% vs. 37%)
• median follow-up of 7 years.
• improved disease-free survival (P = .012)
• local-regional progress-free survival (P = .003)
• Survival rate 55% vs 50% (not sig)
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Neoadjuvant Chemotherapy
• INT-0800(American) study» Confirmed results of MRC study
– 317 patients with T2 to T4a disease – Randomized to 3 cycles of neoadjuvant MVAC prior to cystectomy or
cystectomy alone–Results:
• Improved median survival by almost 3 years (77 months vs 46 months)
• Decreased risk of bladder cancer specific death by 25%
• Improved OS by 5% (p=0.06)
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INT0800
ARM Med Survival Alive at 5 yrs P-value
Surgey 46 Mos 42% .044 (HR .74)
MVAC 77 Mos 57%
33 % grade 3/4 toxicity in the chemo arm20% sepsisNo death
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Tolerability of cisplatin-based neoadjuvant chemotherapy and effect on radical cystectomy
• MVAC regimen: The mortality rate in patients assigned to chemotherapy was 1%, but drug delivery was excellent with only 20%.
• In the USA, gemcitabine and cisplatin (GC), but there is no level 1 evidence. drug delivery exceeding 90%.
No RCT in using GC in neo-adjuvant
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NAC does NOT increase the risk of perioperative morbidity
Presented By Maria De Santis at 2017 Genitourinary Cancers Symposium
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Split dose Cis/Gem – real life data
Presented By Maria De Santis at 2017 Genitourinary Cancers Symposium
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Carboplatin in Neoadjuvant
• Not recommendation in using carboplatin in neoadjuvanttreatment ( not eligible for cisplatin based chemotherapy)
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Can we avoid radical cystectomy in patients who appear to have “responded” to neoadjuvant chemotherapy?
• The answer is no.
• SWOG phase II study. Of the 34 who achieved cT0, 10 had immediate cystectomy. Six of the ten (60%!) were found to have pT2–4.
• Herr HW : reviews outcome of 63 patients receiving pCR post 4 cycles of cisplatin-based chemotherapy and no surgery:
• About a third (36%) died with bladder cancer. The risk of death was high (75%) in patients experiencing recurrent invasive bladder cancer.
Herr HW. Outcome of patients who refuse cystectomy after
receiving neoadjuvant chemotherapy for muscle-invasive bladder
cancer. Eur Urol 2008;54:126 –32.
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• 3 cycles of DD-MVAC every 2 weeks
• (methotrexate 30 mg/m2, vinblastine 3 mg/m2, doxorubicin 30 mg/m2, cisplatin 70mg/m2) on day 1 with G-CSF support
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HD MVAC toxicity
Toxicity Grade
MVAC (n=129)
(%)
HD MVAC
(n=134)
(%) p
Neutropenia 3 46 12 <0.001
4 16 8
Neutropenic fever 26 10 <0.001
1 case of toxic death in each arm
Less WBC toxicity in HD MVAC likely
secondary to GCSF
Toxicities otherwise similar
Sternberg Eur Urol 2006
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Carboplatin in Neoadjuvant
• Not recommendation in using carboplatin in neoadjuvant treatment
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Value of Adjuvant chemotherapy
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Adjuvant in T2N0
•pT2 or less and have no nodal involvement or LVI notrecommended to receive adjuvant chemotherapy
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Slide 13
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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AUA/ASCO/ASTRO/SUO Guidelines: Key Findings
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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AUA/ASCO/ASTRO/SUO Guidelines: Key Findings
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Bladder preservation
“The aim of bladder preservation is to
achieve cancer survival with equivalence to
radical cystectomy while retaining an
anatomically normal functioning bladder”
- T2-3 ( some case of T4a) and
- node negative
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Candidates for preservation
• Solitary tumor <5 cm
• Clinical stage T2-T3a ( not properly indicate for T4)
• No CIS
• No hydronephrosis
• No evidence of LN or distant mets
• Normally functioning bladder
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• 5yr overall survival range 39% - 74%
• Bladder preservation 31% - 60%
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Chemoradiation toxicity
Toxicity %
Grade 4
Salvage cystectomy due to contracted bladder 2
Bowel obstruction requiring surgery 1.5
Grade 3
Bladder capacity < 200cc 3
Grade 2
Frequency/urgency 10
Dysuria 8
Diarrhea 5
Proctitis 2
Rodel 2002 JCO
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Hilighted studies
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Selective Bladder Preservation with Twice-Daily Radiation plus 5-Flourouracil/Cisplatin or Daily Radiation plus Gemcitabine for Patients with Muscle Invasive Bladder Cancer – Primary
Results of NRG/RTOG 0712: A Randomized Phase 2 Multicenter Trial
Presented By John Coen at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Slide 2
Presented By John Coen at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Slide 3
Presented By John Coen at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Slide 7
Presented By John Coen at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Slide 9
Presented By John Coen at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Slide 10
Presented By John Coen at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Preop-CCRT
• Canadian randomized study
• Concurrent CDDP improved pelvic disease
control with preoperative CCRT compared with
RT alone (P = 0.038).
• Preoperative CCRT or RT may be an option
treatment for T ≥4 cm and T3–T4a, especially in
in patients who are not candidates for or decline
cystectomy
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Slide 38
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Adjuv Chemo + XRT vs Adjuv Chemo Alone After Cystectomy: What is This About?
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Adjuv Chemo + XRT vs Adjuv Chemo Alone After Cystectomy: What is This About?
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Adjuv Chemo + XRT vs Adjuv Chemo Alone After Cystectomy: Key Findings-- LRFS
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Adjuv Chemo + XRT vs Adjuv Chemo Alone After Cystectomy: Key Findings-- DFS
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Adjuv Chemo + XRT vs Adjuv Chemo Alone After Cystectomy: Key Findings
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Adjuv Chemo + XRT vs Adjuv Chemo Alone After Cystectomy: Importance
Presented By Sam Chang at 2018 Genitourinary Cancers Symposium: Translating Evidence to Multidisciplinary Care
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Take home massage
• Bladder cancer is genomically complex
• Neoadjuvant produces 5% absolute benefit in survival,
need for MDT in care.
• Combination chemo can prolong symptoms free and OS
in advanced bladder cancer, but, high levels of toxicity.
• Select treatments for patients: fit or unfit patients
• Bladder preservation should be an option of treatment