Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
BLADDER CANCER Non Muscle Invasive vs Muscle Invasive Cystectomy vs Chemoradiotherapy Incidence Fourth most common cancer in men Ninth most common cancer in women Sustained decline in incidence over recent times 60 % reduction in incidence over past 30 years • • Invasive bladder cancer in WA 2012 (note WACR data listed as “bladder and urinary tract” presume includes upper tract TCC) Incidence Deaths 210 men 75 women 70 men 34 women 75% of bladder cancers are non muscle invasive (NMIBC) (2014 EAU Guidelines) Etiology The first of the “industrial” cancers in the 19th century associated with the industrial revolution and the increasing use of chemicals in the textile industry in the English textile and dye industry naphthylamine, aminobiphenyl, combustion gases, coal soot arylamines and aniline dyes β-naphthylamine synthetic dye in the late 1800’s most bladder carcinogens are aromatic amines Smoking also increasing through 18th and 19th centuries bladder cancers 4 times more common in smokers Etiology Phenacetin in old “APC analgesics, esp upper tract TCC Pelvic radiotherapy for CA cervix – 2 to 4 fold increase in bladder cancer Chronic cystitis associated with long term catheters 2 – 10% of spinal patients with long term catheters get CA bladder, 80% SCC • Schistosomiasis and SCC • Cyclophosphamide treatment 9 x increased risk Pathology TCC Transitional cell carcinoma (TCC) 90% of bladder cancers CIS carcinoma in situ = high grade superficial TCC Papillary TCC low grade 15% progression to invasive disease Papillary TCC high grade commonly invasive, life threatening Nested form TCC higher risk than standard TCC, chemosensitive Micropapillary TCC higher risk than standard TCC, not chemosensitive Papillary TCC Pathology SCC Squamous cell carcinoma (SCC) ~ 5% bladder cancers, wide geographic presentation Long term IDCs Schistosomiasis esp Egypt (75%) Not chemosensitive or radiosensitive Treatment is surgical – radical cystectomy Traditionally thought relatively unresponsive to chemotherapy or radiotherapy Pathology Adenocarcinoma Adenocarcinoma ~ 2 % bladder cancers Allegedly associated with chronic UTI Not chemosensitive or radiosensitive Treatment surgical – radical cystectomy Urachal carcinoma Most adenocarcinoma Bladder dome Characteristically massive mucous secretion Treatment partial cystectomy, bladder dome and urachus up to umbilicus Pathology Rarer Histologies Carcinosarcoma Aggressive, not chemosensitive or radiosensitive, 20% five year survival Small cell, neuroendocrine Chem/Radiosensitive, Rx chemoradiotherapy, cystectomy if responds, rare cure • • • • Leiomyosarcoma Surgical treatment, cystectomy. 65% five year survival Pheochromocytoma Younger, 20 – 40 years. Adrenergic blockade and care with TURBT Leukaemia and lymphoma Metastatic tumour Rare, more recently breast metastases. Occasional direct infiltration colorectal Staging TNM Primary tumor (T) TX: Primary tumor cannot be assessed T0: No evidence of primary tumor Ta: Noninvasive papillary carcinoma Tis: Carcinoma in situ (i.e., flat tumor) T1: Tumor invades subepithelial connective tissue T2: Tumor invades muscle pT2a: Tumor invades superficial muscle (inner half) pT2b: Tumor invades deep muscle (outer half) T3: Tumor invades perivesical tissue pT3a: Microscopically pT3b: Macroscopically (extravesical mass) T4: Tumor invades any of the following: prostate, uterus, vagina, pelvic wall, or abdominal wall T4a: Tumor invades the prostate, uterus, vagina T4b: Tumor invades the pelvic wall, abdominal wall [Note: The suffix “m” should be added to the appropriate T category to indicate multiple lesions. The suffix “is” may be added to any T to indicate the presence of associated carcinoma in situ.] Regional lymph nodes (N) NX: Regional lymph nodes cannot be assessed N0: No regional lymph node metastasis N1: Metastasis in a single lymph node 2 cm or smaller in largest dimension N2: Metastasis in a single lymph node larger than 2 cm but 5 cm or smaller in largest dimension; or multiple lymph nodes 5 cm or smaller in largest dimension N3: Metastasis in a lymph node larger than 5 cm in largest dimension Distant metastasis (M) MX: Distant metastasis cannot be assessed M0: No distant metastasis M1: Distant metastasis Americn Joint Committee on Cancer (AJCC) 2002 Bladder Cancer Staging Clinical Presentation Symptoms Frank haematuria 85% of presentations up to 20% of frank haematuria due to malignancy Irritative LUTS / Bladder pain frequency, urgency, bladder pain especially invasive TCC and CIS • Kidney obstruction loin pain impaired renal function Investigation Cystoscopy Flexible cystoscopy, local anaesthetic – initial diagnostic test for haematuria check cystoscopy follow up for previous TCC minimal risk Rigid cystoscopy GA, usually with “TURBT” trans urethral resection bladder tumour take random bladder biopsies with clinically invasive disease check for CIS risks GA, bleeding, infection, bladder perforation tumour chips sent for histopathology – type, subtype and presence invasion Investigation Urine cytology CIS 100% positive High grade TCC 80% positive Low grade TCC only 30% positive Not useful in frank haematuria Minimal usefulness in micro haematuria Most useful in LUTS/Bladder pain if suspect CIS, where cystoscopy may look normal Investigation - Imaging Pyelographic phase important in TCC – “field change” concept and upper tract TCC generally CT pyelogram = 4 phase contrast CT (or IVP) 3% TCC bladder have or develop upper tract TCC More upper tract TCC in CIS bladder and high grade TCC • Staging of invasive bladder cancer CT abdomen and pelvis, generally 4 phase contrast Spread to adjacent organs, regional and distant lymph node spread, upper tract TCC CXR (+/- Chest CT) PET scan Bone scan Treatment – Superficial TCC (NMIBC) TURBT Check cystoscopy - lifelong frequency pending initial differentiation and behaviour generally commencing 3 monthly, then back to 6 then 12 monthly flexible cystoscopy LA • • Intravesical chemotherapy current fashion single dose Mitomycin instilled immediate post op subsequent 6 dose therapy if frequent recurrence to enforce reduced frequency rec Upper tract imaging more so in high grade disease and CIS but consider radiation dose Treatment – Superficial TCC and Intravesical Chemotherapy Frequent recurrence – repeat TURBT problematic Rx intravesical chemo Usually weekly doses for 6 weeks induction +/- “maintenance” monthly single doses. Current fashion Mitomycin, but very expensive (? $1,200 for 40mg, not on PBS) dose and no proven advantage over cheaper agents for low grade TCC, claimed benefit because large molecule c/f thiotepa but actually at 329 kd is actually smaller than doxorubicin (Adriamycin) at 544 kd. Doxorubicin (Adriamycin) dirt cheap on PBS 50 mg in 25 ml (previously $5.60 and repeat, now max cost to patient $37, cost to Government is $137.10 for 135 mg) and probably is probably as effective and a larger molecule than Mitomycin at 544 kd. Prophylactic intravesical instillation therapy with Adriamycin and Mitomycin C in patients with superficial bladder cancer. Tsushima et al. Cancer Chemother. Pharmacol. 1987;20 Suppl:S72-6 The cumulative nonrecurrence rates were 73.6% for Adriamycin, 63.4% for MMC, and 22.5% for controls after a follow-up of 24 months. {Note Mitomycin C dose was 30 mg (40 mg now standard dose) and Adriamycin dose was 50 mg}. • Intravesical chemotherapy is not a cure, but should reduce frequency of recurrence and need for repeated TURBT. “The Grey Zone” Between NMIBC and MIBC High Grade Superficial Disease - T1G3 & CIS NMIBC – TURBT and intravesical chemotherapy with check cystoscopy High grade superficial disease – T1G3 and CIS Geographic differences Mainland Europe, especially Germany, EAU guidelines are complicated but for “Highest risk” (T1G3 + CIS) “explain the risk and consider radical cystectomy”. UK and Australia, traditionally BCG (80% effective) with salvage cystectomy for therapeutic failures (radiotherapy not effective if CIS present). USA AUA Guidelines 2007 recommends intravesical BCG with cystectomy for therapeutic failures. N.B. Careful close follow up required if BCG utilized with “booster dose” protocols. Treatment - CIS Generally high grade and dangerous, high risk of progression to invasive possibly a milder subgroup, but unable to distinguish Can metastasize without clinical invasion Treatment intravesical BCG – weekly dose 6 weeks, then “booster” doses with a range of protocols 80% cure, but reasonable long term failure rate – proceed to cystectomy form of immunotherapy moderate risk – rare systemic BCG life threatening, not if immunosuppressed bladder scarring with obstructive uropathy requires cystectomy • Mitomycin C 40% cure Treatment – “T1G3” TCC Re resection at 6 weeks of tumour scar to re check for muscle invasion Generally BCG in Australia with close follow up high risk of recurrence, progression Cystectomy if muscle invasion shown at 6 week re-resect TURBT scar or if recurrence or progression at close follow-up. Europe generally early cystectomy for “high risk”group – T1G3 with CIS on random bladder biopsies. Radiotherapy Alone for Muscle Invasive TCC ≥ T2 Radiotherapy alone This was standard first line therapy in UK/Australia up until the 1990’s, with “salvage cystectomy” done for failures found at follow up check cystoscopy. Surgical advances came from radical prostatectomy dealing with the prostate dorsal vein complex reducing intra-operative blood loss substantially in men. Now primarily used in cases unfit for cystectomy or in those not wanting cystectomy, usually combined with “radiosensitizing” chemotherapy. 20% cure rate for radiotherapy alone (depending on staging) Not effective if CIS present Check cystoscopy follow up with “proof of cure cysto” 2 – 3 months post treatment “Salvage” cystectomy for failure – up to 40% cure overall Chemoradiotherapy Alone for Muscle Invasive TCC ≥ T2 Tom Ferguson Medical Oncology Lack of good trial data Comparison of radical cystectomy and chemoradiotherapy in patients with locally advanced bladder cancer. Ikeda M, Matsumoto K, Nishi M, Tabata K, Fujita T, Ishiyama H, Hayakawa K, Iwamura M - Asian Pac. J. Cancer Prev. - January 1, 2014; 15 (16); 6519-24 72 patients with locally advanced bladder cancer (T3-4a, N0 or N+, M0) received either radical cystectomy or chemoradiotherapy. Radical cystectomy with bilateral pelvic lymph node dissection including the common iliac region as the standard procedure. Patients in the chemoradiotherapy group received one cycle of MVAC followed by radiotherapy with a half dose of MVAC and then two more cycles of MVAC. Median total radiotherapy dose was 50 Gy. The 3-year progression-free survival (PFS) rates in the radical cystectomy and chemoradiotherapy groups were 56.2% and 25.6%, respectively (p=-0.015) and the 3-year overall survival (OS) rates were 63.5% and 48.1% (p=0.272). Concurrent chemoradiotherapy for clinical stage T2 bladder cancer: report of a single institution. Peyromaure M, Slama J, Beuzeboc P, Ponvert D, Debré B, Zerbib M - Urology - January 1, 2004; 63 (1); 73-7 From 1996 to 2002, 43 patients were treated with concurrent chemotherapy and radiotherapy for clinical Stage T2 bladder cancer. DXRT 24 Gy to pelvis with chemotherapy cisplatinum and 5FU. The overall rate of cystectomy was 25.6%. The rate of cancer specific survival at 3 and 5 years wa s 75% and 60%, respectively. The overall rate of recurrence-free survival at 3 and 5 years was 63% and 33%, respectively. Chemoradiotherapy as a bladder-preservation approach for muscle-invasive bladder cancer: current status and perspectives. Sumiyoshi Y - Int. J. Clin. Oncol. - December 1, 2004; 9 (6); 484-90 In patients who achieve a complete response (CR) after trimodality therapy, 5-year survival rates of more than 50%, the same as those of radical cystectomy, can be achieved and 70% of this group will retain an intact functional bladder. • TROG trial 02.03 Trans Tasman Radiation Oncology Group Comparison of radiotherapy alone (64 Gy) with chemoradiotherapy (weekly infusion of cisplatinum with 64 Gy radiotherapy. Final acrual 67 patients finished recruitment in 2007 ? Surgery for Muscle Invasive TCC ≥ T2 • • Partial cystectomy Little data Possible use in small solid tumours in dome (standard for urachal adenocarcinoma). Radical cystectomy Cystoprostatectomy in males. Cystectomy +/- hysterectomy and bilateral salpingo oophorectomy in females. Usually with regional lymphadenectomy. Major surgery with moderate risks. 2 – 3% mortality. Many patients unfit for surgery because of co morbidities, mostly cardiorespiratory. Older patients have higher risks. Cure Rates for Cystectomy Overall 5 year recurrence free survival post radical cystectomy for TCC: pT2 74% pT3 52% pT4 36% Radical Cystectomy for Bladder Cancer Today—A Homogeneous Series Without Neoadjuvant Therapy Madersbacher, Studer et al Journal of Clinical Oncology Vol 21, No 4 (February 15), 2003: pp 690-696 University of Bern, Switzerland 577 patients that had cystectomy and pelvic lymphadenectomy between 1985 and 2000 • Metanalysis circa 2004 pT2 66% pT3 35% pT4 27% Ileal Conduit Urinary Diversion • Ileal conduit urinary diversion Standard management for urinary output for 60 years Complications: Bleeding Sepsis – perioperative and long term Uretero-ileal anastomotic strictures Para-stomal hernia (recent trial on mesh reinforcement) Stomal stenosis Stomal prolapse Bowel obstruction – early and late Bowel anastomosis breakdown Incisional hernias Impotence in men Sexual dysfunction in women Metabolic acidosis, especially in those with impaired renal function Ileal Conduit Urinary Diversion Bladder Reconstruction Bladder reconstruction “neobladder” Uses “detubularized” bowel segments Larger procedure, generally done in younger patients Orthotopic with suture to native urethra ~ 50% void with abdominal straining ~ 50% clean intermittent self catheterize some continence issues nocturnal incontinence problematic with smaller reservoirs Heterotopic with continent stoma self catheterized All have a risk of adenocarcinoma in neobladder, check cystoscopies after 5 years Bladder Reconstruction Neo-adjuvant and Adjuvant Chemotherapy with Cystectomy • Since early 1990’s • Improvement in curative outcomes – Tom Ferguson, Medical Oncology