Cancer Association of South Africa (CANSA)

Transcription

1 Cancer Assciatin f Suth Africa (CANSA) Fact Sheet n Bladder Cancer Intrductin The urinary bladder is the rgan that cllects urine excreted by the kidneys befre dispsal by means f urinatin. It is a hllw muscular, and distensible (elastic) rgan. The bladder is situated n the pelvic flr. Urine enters the bladder via the ureters and exits via the urethra. [Picture Credit: Male Urinary Tract] In males, the base f the bladder lies between the rectum and the pubic symphysis. It is superir (abve) t the prstate, and separated frm the rectum by the rectvesical excavatin. In females, the bladder is situated inferir (belw) t the uterus (wmb) and anterir (in frnt) t the vagina. Its maximum capacity is lwer than in males. It is separated frm the uterus by the vesic-uterine excavatin. In infants and yung children, the urinary bladder is in the abdmen even when empty. [Picture Credit: Female Urinary Tract] When the bladder is empty it is situated entirely within the pelvis. As it fills with urine its superir (upper) surface gradually rises int the abdminal cavity carrying with it its peritneal cvering. The bladder is lined by layers f muscle tissue that stretch t accmmdate urine. The nrmal capacity f the bladder is 400 t 600 ml. During urinatin, the bladder muscles cntract, and tw sphincters (valves) pen t allw urine t flw ut. Urine exits the bladder int the urethra, which carries urine ut f the bdy. Because it passes thrugh the penis, the urethra is lnger in men (20cm) than in wmen (5cm) - (WebMD). Nvember 2017 Page 1

2 Bladder Cancer Bladder cancer is cancer that frms in tissues f the bladder (the rgan that stres urine). Mst bladder cancers are transitinal cell carcinmas (cancer that begins in cells that nrmally make up the inner lining f the bladder). Other types include squamus cell carcinma (cancer that begins in thin, flat cells) and adencarcinma (cancer that begins in cells that make and release mucus and ther fluids). The cells that frm squamus cell carcinma and adencarcinma develp in the inner lining f the bladder as a result f chrnic irritatin and inflammatin (Natinal Cancer Institute). Incidence f Bladder Cancer in Suth Africa Accrding t the Natinal Cancer Registry (2013) the fllwing number f bladder cancer cases was histlgically diagnsed in Suth Africa during 2013: Grup - Males 2013 Actual N f Cases Estimated Lifetime Risk Percentage f All Cancers All males 952 1:147 2,65% Asian males 44 1:148 5,33% Black males 135 1:653 1,25% Clured males 150 1:85 3,58% White males 623 1:54 3,09% Grup - Females 2013 Actual N f Cases Estimated Lifetime Risk Percentage f All Cancers All females 307 1:709 0,84% Asian females 16 1:340 1,54% Black females 98 1: ,63% Clured females 44 1:385 1,07% White females 150 1:275 1,94% The frequency f histlgically diagnsed cases f bladder cancer in Suth Africa fr 2013 was as fllws (Natinal Cancer Registry, 2013): Grup - Males All males Asian males Black males Clured males White males Grup - Females All females Asian females Black females Clured females White females N.B. In the event that the ttals in any f the abve tables d nt tally, this may be the result f uncertainties as t the age, race r sex f the individual. The ttals fr all males and all females, hwever, always reflect the crrect ttals. Nvember 2017 Page 2

3 Risk Factrs fr Bladder Cancer The fllwing are risk factrs fr bladder cancer: Use f tbacc prducts - smking cigarettes, cigars r pipe tbacc may increase the risk f bladder cancer by causing harmful chemicals t accumulate in the urine. When smking, the bdy prcesses the chemicals in the smke and excretes sme f it in the urine. These harmful chemicals may damage the lining f the bladder, which can increase the risk fr cancer Obesity - Cmpared with nrmal-weight individuals (bdy mass index [BMI] kg/m 2 ), pre-bese and bese individuals (BMI and 30 r greater, respectively) had a 7% and 10% increased risk f bladder cancer, respectively, the researchers reprted in PLOS One. Increasing age - the risk fr bladder cancer increases with age. Bladder cancer can ccur at any age, but it is rarely fund in peple yunger than 40. Being white - whites have a greater risk fr bladder cancer than d peple f ther races. Being a male - men are mre likely t develp bladder cancer than wmen. Expsure t certain chemicals - the kidneys play a key rle in filtering harmful chemicals frm the bldstream and mving them t the bladder. Because f this, it is thught that being arund certain chemicals may increase the risk fr bladder cancer. Chemicals linked t bladder cancer risk include arsenic and chemicals used in the manufacture f dyes, rubber, leather, textiles and paint prducts. Industries carrying the highest risks include the makers f rubber, leather, textiles, and paint prducts as well as printing cmpanies. Other wrkers with an increased risk fr develping bladder cancer include painters, machinists, printers, hairdressers (likely because f heavy expsure t hair dyes) and truck drivers (likely because f expsure t diesel fumes). Previus cancer treatment - treatment with the anti-cancer drug cyclphsphamide (Cytxan) increases the risk fr bladder cancer. Peple wh received radiatin treatments aimed at the pelvis fr a previus cancer may als have an elevated risk fr develping bladder cancer. Chrnic bladder inflammatin - chrnic r repeated urinary infectins r inflammatins (cystitis), such as what happens with lng-term use f a urinary catheter, may increase the risk fr a squamus cell bladder cancer. In sme areas f the wrld including Suth Africa, squamus cell carcinma is linked t chrnic Nvember 2017 Page 3

4 bladder inflammatin caused by the parasitic infectin knwn as schistsmiasis. [Picture Credit: Schistsma haematbium] Schistsmiasis (Bilharzia) is a parasitic infectin that ccurs thrughut Africa and the Middle East. One frm f the parasite, schistsma haematbium is linked t bladder cancer and it was estimated t have caused arund cases f the disease wrldwide in Persnal r family histry f cancer a histry f previusly having had bladder cancer, makes ne mre likely t get it again. If ne r mre immediate relatives have a histry f bladder cancer, there is als an increased risk fr the disease, althugh it is rare fr bladder cancer t run in families. A family histry f hereditary nn-plypsis clrectal cancer, als called Lynch syndrme can increase the risk fr cancer f the urinary system, as well as the cln, uterus, varies and ther rgans. Bladder birth defects - befre birth, there is a cnnectin between the belly buttn and the bladder. This cnnectin, called the urachus, nrmally ges away befre birth. If part f this cnnectin remains after birth, it culd becme cancerus. Cancers that start in the urachus are usually adencarcinmas, which are made up f malignant gland cells. Abut ne third f the adencarcinmas f the bladder start here. Hwever, this is still rare, accunting fr less than a half f 1% f all bladder cancers. Anther rare birth defect called exstrphy greatly increases a persn s risk fr develping bladder cancer. In bladder exstrphy, bth the bladder and the abdminal wall in frnt f the bladder fail t clse cmpletely during develpment and are fused tgether. This leaves the inner lining f the bladder expsed utside the bdy. Surgery sn after birth can clse the bladder and abdminal wall (and repair ther related defects), but patients wh have this are still at increased risk fr urinary infectins and bladder cancer. Inherited gene mutatins - a small number f peple inherit a gene syndrme that increases their risk fr bladder cancer. Fr example: A mutatin f the retinblastma (RB1) gene can cause cancer f the eye in infants, and als increases the risk f bladder cancer Cwden disease, caused by mutatins in a gene called PTEN, is linked mainly t cancers f the breast and thyrid. Peple with this disease als have a higher risk f bladder cancer Lynch syndrme (als knwn as hereditary nn-plypsis clrectal cancer, r HNPCC) is mainly linked t cln and endmetrial cancer. Peple with this syndrme als have an increased risk f bladder cancer, as well as cancer f the ureters. Researchers have studied the effects f mutatins in several genes, including FGFR3, RB1, HRAS, TP53, and TSC1, n the frmatin and grwth f bladder tumurs. Each f these genes plays a critical rle in regulating cell divisin by preventing cells frm dividing t rapidly r in an uncntrlled way. Alteratins in these genes may help explain why sme bladder cancers grw and spread mre rapidly than thers. Nvember 2017 Page 4

5 Deletins f part r all f chrmsme 9 are cmmn events in bladder tumurs. Researchers believe that several genes that cntrl cell grwth and divisin are prbably lcated n chrmsme 9. They are wrking t determine whether a lss f these genes plays a rle in the develpment and prgressin f bladder cancer. Mst f the genetic changes assciated with bladder cancer develp in bladder tissue during a persn's lifetime, rather than being inherited frm a parent. Sme peple, hwever, appear t inherit a reduced ability t break dwn certain chemicals, which makes them mre sensitive t the cancer-causing effects f tbacc smke and industrial chemicals. Lw fluid cnsumptin - nt drinking enugh fluids may increase the risk fr bladder cancer. Peple wh drink a lt f fluids each day have a lwer rate f bladder cancer. This is thught t be because they empty their bladders ften. By ding this, they keep chemicals frm lingering in the urinary bladder. Hrmnal factrs - tw chrt studies shw a 60% increase in the risk fr bladder cancer in wmen underging menpause befre the age f cmpared t 48 r later. Wmen wh have had a bilateral phrectmy als have a 60% increased risk fr bladder cancer Fds and drinks - tw Chinese chrt studies have reprted a significant increase in risk with higher cnsumptin f sya fds. This assciatin is nt clearly understd: ne thery is that the chemical reactin f chlrine in water with humic substances in beans during fermentatin may act as a bladder carcingen. (May Clinic; American Cancer Sciety; Cancer Research UK; Cancer.Net; Genetics Reference; Cancer Treatment Centers f America; Renal & Urlgy News). Signs and Symptms f Bladder Cancer Peple with bladder cancer may experience the fllwing symptms r signs. Smetimes, peple with bladder cancer d nt shw any f these symptms. Or, these symptms may be caused by a medical cnditin that is nt cancer. Bladder cancer usually des nt cause symptms that specifically indicate cancer: bld in urine (haematuria) urine may appear dark yellw, bright red r cla clured. r urine may appear nrmal, but bld may be detected in a micrscpic examinatin f the urine frequent urinatin bladder spasm painful urinatin (dysuria) urgent need t urinate inability t urinate reduced bladder capacity back pain Nvember 2017 Page 5

6 pelvic pain Symptms f advanced bladder cancer may include: pain unexplained appetite lss weight lss Smetimes when the first symptms f bladder cancer appear, the cancer has already spread t anther part f the bdy. The symptms depend n where the cancer has spread t. Fr example, cancer that has spread t the lungs may cause a cugh r shrtness f breath, cancer that has spread t the liver may cause abdminal pain r jaundice (yellwing f the skin and whites f the eyes) and cancer that has spread t the bne may cause bne pain r a bne break. (May Clinic; Cancer.Net; Canadian Cancer Sciety). Diagnsis f Bladder Cancer Bladder cancers are usually fund when a persn ges t the dctr because f signs r symptms they are having. If bladder cancer is suspected, tests will be needed t cnfirm the diagnsis. bld in the urine changes in bladder habits r irritating symptms such as: frequency: having t urinate mre ften than usual dysuria: feeling pain r burning during urinatin urgency: feeling as if yu need t g right away, even when the bladder is nt full medical histry and physical exam cystscpy - If bladder cancer is suspected the dctr will recmmend a cystscpy. Fr this exam, a urlgist places a cystscpe a slender tube with a light and a lens r a small vide camera n the end thrugh the pening f the urethra and advances it int the bladder. Sterile salt water is then injected thrugh the scpe t expand the bladder and allw the dctr t lk at the bladder lining. labratry tests urine cytlgy - fr this test, a sample f urine is lked at under a micrscpe t see if it cntains any cancer r pre-cancer cells. Cytlgy is als dne n any bladder washings taken when the cystscpy was dne. Cytlgy can help find sme cancers, but this test is nt perfect. Nt finding cancer n this test des nt always mean that the patient is cancer free. urine culture urine tumur marker test a number f different urine tests lk fr specific substances released by bladder cancer cells. Nvember 2017 Page 6

7 bipsy - a bipsy is the remval f a sample f tissue t see if it is cancer. The tissue that is remved is sent t the labratry where it is lked at by a pathlgist, a dctr wh specialises in diagnsing diseases by examining tissues with a micrscpe. If bladder cancer is suspected a bipsy is needed t cnfirm the diagnsis. bladder bipsies - Bladder bipsy samples are mst ften btained during cystscpy. A bipsy can shw whether cancer is present and what type f bladder cancer it is. If bladder cancer is fund, tw imprtant features are its invasiveness and grade. bipsies t lk fr cancer spread - if imaging tests suggest the cancer may have spread utside f the bladder, a bipsy is the nly way t be sure. In sme cases, bipsy samples f suspicius areas are btained during the surgery t remve the bladder cancer. anther way t get a bipsy sample is t use a thin, hllw needle t take a small piece f tissue frm the abnrmal area. This is knwn as a needle bipsy, and it can allw the dctr t take samples withut an peratin. Needle bipsies are smetimes dne using a CT scan r ultrasund t help guide the bipsy needle int the abnrmal area. imaging tests - imaging tests use x-rays, magnetic fields, sund waves, r radiactive substances t create pictures f the inside f yur bdy intravenus pyelgram - an intravenus pyelgram (IVP), als called an intravenus urgram (IVU) is an x-ray f the urinary system taken after injecting a special dye int a vein. This dye is remved frm the bldstream by the kidneys and then passes int the ureters and bladder. The dye utlines these rgans n x-rays and helps find urinary tract tumurs. Sme peple may have allergic reactins t the dye, s it s imprtant t tell yur dctr if yu have any allergies r have ever had any reactins t x-ray dyes retrgrade pyelgram - fr this test, a catheter (thin tube) is placed thrugh the urethra and up int the bladder r int a ureter. Then a dye is injected thrugh the catheter t make the lining f the bladder, ureters, and kidneys easier t see n x-rays cmputed tmgraphy (CT) scan - The CT scan is an x-ray test that prduces detailed crss-sectinal images f yur bdy. Instead f taking ne picture, like a standard x-ray, a CT scanner takes many pictures as it rtates arund yu. A cmputer then cmbines these pictures int an image f a slice f yur bdy magnetic resnance imaging (MRI) scan - Like CT scans, MRI scans prvide detailed images f sft tissues in the bdy. But MRI scans use radi waves and strng magnets instead f x-rays ultrasund - Ultrasund (ultrasngraphy) uses sund waves t create pictures f internal rgans. It can be useful in determining the size f a bladder cancer and whether it has spread beynd the bladder t nearby rgans r tissues. It can als be used t lk at the kidneys. chest x-ray - A chest x-ray may be dne t lk fr spread f bladder cancer t the lungs. This test is nt needed if a CT scan f the chest has been dne. bne scan - A bne scan can help lk fr cancer that has spread t bnes. Dctrs dn t usually rder this test unless yu have symptms such as bne pain, r if bld tests shw the cancer might have spread t yur bnes. Fr this test, a small amunt f lw-level radiactive material is injected int a Nvember 2017 Page 7

8 vein (intravenusly, r IV). The substance settles in areas f damaged bne thrughut the entire skeletn ver the curse f a cuple f hurs. Yu then lie n a table fr abut 30 minutes while a special camera detects the radiactivity and creates a picture f the skeletn. The picture is nt detailed like an MRI r CT scan, but it shws pssible areas f cancer spread t all f the bnes in the bdy at nce. Areas f active bne changes appear as ht spts n the skeletn that is, they attract the radiactivity. These areas may suggest the presence f cancer, but ther bne diseases can als cause the same pattern. T distinguish amng these cnditins, ther imaging tests such as plain x-rays, MRI scans, r even a bne bipsy might be needed. (American Cancer Sciety; May Clinic; MacMillan Cancer Supprt; Memrial Slan-Kettering Cancer Center). Types f Bladder Cancer Transitinal cell bladder cancer - smetimes called urthelial cancer. It is a cancer that develps frm the cells f the bladder lining (urthelium). The cells are called transitinal cells. When the bladder is empty, they are all bunched tgether. When the bladder is full, they are stretched ut int a single layer. Because they line the bladder, these cells cme int cntact with waste prducts in the urine that may cause cancer, such as chemicals in cigarette smke Nn muscle invasive (superficial) bladder cancer - superficial bladder cancers are early stage transitinal cell bladder cancer. The cancer is nly in the lining f the bladder and hasn't grwn int the deeper layers f the bladder wall. It usually appears as small grwths, shaped like mushrms, grwing ut f the bladder lining. This is called papillary bladder cancer. Yur surgen can remve these grwths and they may never cme back Invasive bladder cancer - Transitinal cell bladder cancer can becme invasive. This means it has grwn int the muscle layer f the bladder, r beynd. Sme peple have invasive bladder cancer when they are first diagnsed. Invasive bladder cancer needs mre intensive treatment than superficial bladder cancer. This is because there is a risk that it culd spread t ther parts f the bdy. Invasive bladder cancers are divided int T2, T3 r T4. This is part f the staging f bladder cancer. There is mre abut the stages f bladder cancer in the sectin abut treating bladder cancer Squamus cell bladder cancer - Squamus cells are flat cells that make up the mist, skin like, tissues lining the bdy rgans. Up t 8 ut f every 100 (8%) bladder cancers in the UK are squamus cell cancers. They are mre cmmn in develping cuntries where a wrm infectin called bilharzia r schistsmiasis is widespread. Adencarcinma f the bladder - This is a very rare type f bladder cancer. Between 1 and 2 ut f every 100 peple diagnsed with bladder cancer have this type (1 t 2%). It is a cancer that develps frm the cells in the lining f the bladder that prduce mucus. All the mist, skin like, tissues lining the bdy have sme gland cells that prduce mucus. Rare types f bladder cancer - It is pssible t get a cancer f the bladder muscle r ther structural tissues, rather than the bladder lining. Cancers that start in the bladder lining are called sarcmas and are very rare. If yu are lking fr infrmatin abut sarcma f the bladder, yu need t g t the sectin n sft tissue sarcma Small cell cancer f the bladder - it is very rare Cancer that has spread t the bladder - Smetimes, a cancer that has started elsewhere in the bdy can spread t the bladder. Fr example: Nvember 2017 Page 8

9 prstate cancer cancer f the back passage (rectum) cancer f the vary wmb cancer (cancer f the uterus) cancer f the cervix These cancers are called secndary cancer. This sectin is nly abut primary bladder cancer. Secndary cancer cells are the same type as the primary cancer. S the treatment will be the same as fr the primary cancer. If yu have a cancer that has spread t the bladder, yu need t lk at the sectin fr yur type f primary cancer t get the right infrmatin. (Cancer Research UK; Weill Crnell Medical Cllege; MD Andersn Cancer Center). Reducing the Risk fr Bladder Cancer Bladder cancer cannt be prevented altgether, but ne can reduce the risk fr getting it. stp smking - smkers are much mre likely t get bladder cancer than nnsmkers. aviding expsure t industrial chemicals, such as benzene substances and arylamines. Occupatinal expsure frm wrking with dyes, rubbers, textiles, paints, leathers, and chemicals raises ne s risk fr bladder cancer drinking water thrughut the day - in thery, drinking liquids, especially water, may dilute txic substances that may be cncentrated in ne s urine and flush them ut f ne s bladder mre quickly. Studies have been incnclusive as t whether drinking water will decrease the risk f bladder cancer chse a variety f fruits and vegetables - chse a diet rich in a variety f clurful fruits (in seasn) and vegetables. The antixidants in fruits and vegetables may help reduce ne s risk f cancer. Take at least five prtins f vegetables and fresh fruit (in seasn) each day limit the intake f smked r cured meats limit the intake f ther prcessed fds research suggests that peple with adequate vitamin B 6, beta-cartene, and selenium in their diets have a reduced risk f develping bladder cancer. wrk safely arund carcingenic chemicals - fllw safety guidelines t avid expsure (WebMD; Life is Beautiful; May Clinic; MD Andersn Cancer Center). Staging f Bladder Cancer The fllwing staging is used fr bladder cancer: Knwing the stage helps the dctr t decide what kind f treatment is best. It can als help predict a patient's prgnsis (chance f recvery). There are different stage descriptins fr different types f cancer. Fr bladder cancer, the stage is determined based n the results f the sample remved during a TURBT and whether the cancer has spread t ther parts f the bdy, which is determined by imaging tests, a physical examinatin, and labratry tests. A TURBT is a Nvember 2017 Page 9

10 prcedure in which bladder tumurs can be remved frm the bladder wall. This is a prcedure perfrmed cmpletely with a scpe that is inserted thrugh the urethra int the bladder. It is generally perfrmed in the hspital setting as an utpatient with the patient anaesthetised. One tl dctrs use t describe the stage is the TNM system. This system judges three factrs: the tumur itself, the lymph ndes arund the tumur, and if the tumur has spread t ther parts f the bdy. The results are cmbined t determine the stage f cancer fr each persn. There are five stages f bladder cancer: stage 0 (zer) and stages I thrugh IV (ne thrugh fur). The stage prvides a cmmn way f describing the cancer, s dctrs can wrk tgether t plan the best treatments. TNM is an abbreviatin fr tumur (T), nde (N), and metastasis (M). Dctrs lk at these three factrs t determine the stage f cancer: Hw large is the primary tumur and hw deeply has it invaded the tissue? (Tumur, T) Has the tumur spread t the lymph ndes? (Nde, N) Has the cancer metastasized t ther parts f the bdy? (Metastasis, M) Tumur. Using the TNM system, the T plus a letter and/r number (0 t 4) is used t describe the size and lcatin f the tumur. Sme stages are als divided int smaller grups that help describe the tumur in even mre detail. If there is mre than ne tumur, the lwercase letter m (multiple) is added t the T stage categry. Specific tumur stage infrmatin is listed belw: TX: the primary tumur cannt be evaluated T0: there is n evidence f a primary tumur in the bladder Ta: this refers t nn-invasive papillary carcinma. This kind f grwth ften is fund n a small sectin f tissue that easily can be remved with TURBT and tends t be recurrent Tis: this stage is carcinma (cancer) in situ, r flat tumur. This means that the cancer is nly fund in cells within the lining f the bladder. The dctr may als call it nnmuscle-invasive/superficial bladder cancer r nninvasive flat carcinma (the cancer is n r near the surface f the bladder). This type f bladder cancer ften cmes back after treatment, usually as anther nninvasive cancer in the bladder T1: the tumur has spread t the sub-epithelial cnnective tissue (the tissue belw the inside lining f the bladder) T2: the tumur has spread t the muscle f the bladder wall T2a: the tumur has spread t the inner half f the muscle f the bladder wall (which may be called the superficial muscle.) T2b: the tumur has spread t the deep muscle f the bladder (the uter half f the muscle) T3: the tumur has grwn int the peri-vesical tissue (the fatty tissue that surrunds the bladder) T3a: T3b: the tumur has grwn int the peri-vesical tissue, as seen thrugh a micrscpe the tumur has grwn int the peri-vesical tissue macrscpically, meaning that the tumur(s) is large enugh t be seen during imaging tests r t be seen r felt by the dctr Nvember 2017 Page 10

11 T4: the tumur has spread t any f the fllwing: the abdminal wall, the pelvic wall, a man s prstate r seminal vesicle (the tube(s) that carry semen), r a wman s uterus r vagina T4a: the tumur has spread t the prstate, uterus, r vagina T4b: the tumur has spread t the pelvic wall r the abdminal wall Nde. The N in the TNM staging system stands fr lymph ndes, the tiny, bean-shaped rgans that help fight infectin. Lymph ndes near where the cancer started, within the true pelvis (called hypgastric, bturatr, iliac, perivesical, pelvic, sacral, and presacral lymph ndes), are called reginal lymph ndes. Lymph ndes in ther parts f the bdy are called distant lymph ndes. NX: the reginal lymph ndes cannt be evaluated N0: the cancer has nt spread t the reginal lymph ndes N1: the cancer has spread t a single reginal lymph nde in the pelvis N2: the cancer has spread t mre than ne reginal lymph nde in the pelvis N3: the cancer has spread t the cmmn iliac lymph ndes, which are lcated behind the majr arteries in the pelvis, abve the bladder Distant metastasis. The M in the TNM system indicates whether the cancer has spread t ther parts f the bdy. M0: the disease has nt metastasized M1: there is distant metastasis Cancer stage gruping Dctrs assign the stage f the bladder cancer by cmbining the T, N, and M classificatins. Stage 0a: This is an early cancer that is nly fund n the surface f the inner lining f the bladder. Cancer cells are gruped tgether and can ften be easily remved. The cancer has nt invaded the muscle r cnnective tissue f the bladder wall. This type f bladder cancer is als called nn-invasive papillary urthelial carcinma (Ta, N0, M0). Stage 0is: This stage f cancer, als knwn as flat r carcinma in situ, is fund nly n the inner lining f the bladder. It has nt grwn in tward the hllw part f the bladder, and it has nt spread t the thick layer f muscle r cnnective tissue f the bladder (Tis, N0, M0). This is always a high-grade cancer (see Grading, belw). Stage I: The cancer has grwn thrugh the inner lining f the bladder t the lamina prpria. It has nt spread t the thick layer f muscle in the bladder wall r t lymph ndes r ther rgans (T1, N0, M0). Stage II: The cancer has spread int the thick muscle wall f the bladder (als called invasive cancer r muscle-invasive cancer). It has nt reached the fatty tissue surrunding the bladder and has nt spread t the lymph ndes r ther rgans (T2, N0, M0). Nvember 2017 Page 11

12 Stage III: The cancer has spread thrughut the muscle wall t the fatty layer f tissue surrunding the bladder. It may als have spread t the prstate in a man r the uterus and vagina in a wman. It has nt spread t the lymph ndes r ther rgans (T3 r T4a, N0, M0). Stage IV: Any f these cnditins: the tumur has spread t the pelvic wall r the abdminal wall but nt t the lymph ndes r ther parts f the bdy (T4b, N0, M0) the tumur has spread t ne r mre reginal lymph ndes but nt t ther parts f the bdy (any T, N1-3, M0) the tumur may r may nt have spread t the lymph ndes but has spread t ther parts f the bdy (any T, any N, M1) Recurrent Bladder Cancer: Recurrent cancer is cancer that cmes back after treatment. If there is a recurrence, the cancer may need t be staged again (called re-staging) using the system abve. Lymph ndes, bnes, lung, liver, and peritneum are the mst cmmn sites f metastasis frm bladder cancer. Tumurs in a mre advanced T categry and thse with atypical histlgic features metastasize earlier. Tumurs with atypical histlgic features als have a higher frequency f peritneal metastasis (Shinagare, et al). Grading Tumur grade. In additin t the TNM system, the cancer may als be evaluated and assigned a grade (G). Dctrs use the term grade t describe hw much the tumur tissue lks like nrmal bladder tissue under a micrscpe. Many urlgic surgens classify grading based n the chance that the cancer will recur (cme back after treatment) r prgress (grw and spread), and plan their treatment based n the grade, using the fllwing categries: Papillma. This is als called benign papillary urthelial neplasm f lw malignant ptential (PUNLMP). These types f cancer may recur but have a lw risk f prgressing. Lw grade. These types f cancer are mre likely t recur and prgress cmpared with PUNLMP. High grade. These types f cancer are the mst likely t recur and prgress. Mre recently, the Wrld Health Organizatin (WHO) has recmmended changing bladder cancer grading t nly tw categries: 1) well-differentiated r lw grade, and 2) prly differentiated r high grade. This is the system that is used in the latest versin f the American Jint Cmmittee n Cancer (AJCC) Staging System. Nvember 2017 Page 12

13 (Cancer.Net). Prgnsis (Outlk) Medical prfessinals advise that early detectin and prmpt treatments are the key a psitive bladder-cancer prgnsis. The utlk fr peple with bladder cancer varies dramatically depending n the stage f the cancer at the time f diagnsis. Nearly 90% f peple treated fr superficial bladder cancer (Ta, T1, CIS) survive fr at least five years after treatment Only abut 5% f peple with metastatic bladder cancer survive fr at least tw years after diagnsis Recurrent cancer indicates a mre aggressive type and a pr utlk fr lng-term survival fr patients with high-stage r high-grade bladder cancer. Recurrent lwgrade superficial bladder cancer is rarely life threatening (Acts Bladder Cancer Assciatin; emedicinehealth). Where Bladder Cancer Spreads t Shuld bladder cancer spread t ther parts f the bdy, it wuld mst prbably spread as indicated belw: Cancer Type: Bladder Breast Cln Clrectal Kidney Lung Melanma Ovary Pancreas Prstate Stmach Thyrid Uterus Nn-melanma skin cancer (Natinal Cancer Institute). Main Sites f Metastasis (Spread) Bne, liver, lung Bne, brain, liver, lung Liver, lung Liver, lung, peritneum (lining f abdmen) Adrenal gland, bne, brain, liver, lung Adrenal gland, bne, brain, liver, ther lung Bne, brain, liver, lung, skin, muscle Liver, lung, peritneum (lining f abdmen) Liver lung, peritneum (lining f abdmen) Adrenal gland, bne, liver, lung Liver, lung, peritneum (lining f abdmen), varies Bne, liver, lung Bne, liver, lung, peritneum (lining f abdmen), vagina Very rare: lymph ndes, lung, bne (if in head/neck regin) Treatment f Bladder Cancer The fllwing cmprises standard treatment fr bladder cancer: Surgery - ne f the fllwing types f surgery may be dne: Transurethral resectin (TUR) with fulguratin - surgery in which a cystscpe (a thin lighted tube) is inserted int the bladder thrugh the urethra. A tl with a small wire lp n the end is then used t remve the cancer r t burn the tumur away with high-energy electricity. This is knwn as fulguratin Radical cystectmy - surgery t remve the bladder and any lymph ndes and nearby rgans that cntain cancer. This surgery may be dne when the bladder Nvember 2017 Page 13

14 cancer invades the muscle wall, r when superficial cancer invlves a large part f the bladder. In men, the nearby rgans that are remved are the prstate and the seminal vesicles. In wmen, the uterus, the varies, and part f the vagina are remved. Smetimes, when the cancer has spread utside the bladder and cannt be cmpletely remved, surgery t remve nly the bladder may be dne t reduce urinary symptms caused by the cancer. When the bladder must be remved, the surgen creates anther way fr urine t leave the bdy Segmental cystectmy - surgery t remve part f the bladder. This surgery may be dne fr patients wh have a lw-grade tumur that has invaded the wall f the bladder but is limited t ne area f the bladder. Because nly a part f the bladder is remved, patients are able t urinate nrmally after recvering frm this surgery Urinary diversin - surgery t make a new way fr the bdy t stre and pass urine. Radiatin therapy - radiatin therapy is a cancer treatment that uses high-energy x-rays r ther types f radiatin t kill cancer cells r keep them frm grwing. There are tw types f radiatin therapy. External radiatin therapy uses a machine utside the bdy t send radiatin tward the cancer. Internal radiatin therapy uses a radiactive substance sealed in needles, seeds, wires, r catheters that are placed directly int r near the cancer. The way the radiatin therapy is given depends n the type and stage f the cancer being treated. Chemtherapy - chemtherapy is a cancer treatment that uses drugs t stp the grwth f cancer cells, either by killing the cells r by stpping them frm dividing. When chemtherapy is taken by muth r injected int a vein r muscle, the drugs enter the bldstream and can reach cancer cells thrughut the bdy (systemic chemtherapy). When chemtherapy is placed directly int the cerebrspinal fluid, an rgan, r a bdy cavity such as the abdmen, the drugs mainly affect cancer cells in thse areas (reginal chemtherapy). Bladder cancer may be treated with intravesical (int the bladder thrugh a tube inserted int the urethra) chemtherapy. The way the chemtherapy is given depends n the type and stage f the cancer being treated. Periperative Chemtherapy (Neadjuvant r Adjuvant) Regimen: Dse-dense methtrexate +vinblastine + dxrubicin + cisplatin (DDMVAC) with grwth factr supprt Gemcitabine + cisplatin Cisplatin + methtrexate + vinblastine (CMV) Dsing: Day 1: Methtrexate 30mg/m 2 IV Day 2: Vinblastine 3mg/m 2 IV, plus dxrubicin 30mg/m 2 IV, plus cisplatin 70mg/m 2 IV Day 4: Granulcyte clny-stimulating factr (G-CSF) 240µg/m 2 SQ fr 7 cnsecutive days (day 4 thrugh 10). May be extended fr up t a ttal f 14 cnsecutive days. Repeat every 2 weeks fr 3-4 cycles Day 1, 8 and 15: Gemcitabine 1 000mg/m 2 IV ver minutes Day 2: Cisplatin 70mg/m 2 Repeat every 2 weeks fr 3-4 cycles Day 1: Methtrexate 30mg/m 2 IV blus plus vinblastine 4mg/m 2 IV blus Day 2: Cisplatin 100mg/m 2 IV infusin; fllwed by hydratin; fllwed by leucvrin 15mg PO f IV every 6 hurs fr 4 dses (cmmencing 24 hurs after methtrexate n day 1) Day 8: Methtexate 30mg/m 2 IV blus plus vinblastine 4mg/m 2 IV blus Nvember 2017 Page 14

15 (Cancer Therapy Advisr) Day 9: Leucvrin 15mg PO every 6 hurs fr 4 dses after methtrexate n day 8 Repeat every 3 weeks fr 3 cycles First-Line Chemtherapy fr Metastatic Disease Regimen: Gemcitabine + cisplatin (Categry 1) DDMVAC with grwth factr supprt (Categry 1) (Cancer Therapy Advisr) Dsing: Days 1, 8 and 15: Gemcitabine 1,000mg/m2 IV ver minutes Day 2: Cisplatin 70mg/m2. Repeat every 4 weeks fr a maximum f 6 cycles. Day 1: Methtrexate 30mg/m2 IV Day 2: Vinblastine 3mg/m2 IV, plus dxrubicin 30mg/m2 IV, plus cisplatin 70mg/m2 IV Day 4: G-CSF 240μg/m2 SQ fr 7 cnsecutive days (days 4 thrugh 10). May be extended fr up t a ttal f 14 cnsecutive days. Repeat every 2 weeks fr 3 4 cycles. OR Day 1: Methtrexate 30mg/m2 IV Day 2: Vinblastine 3mg/m2 IV, plus dxrubicin 30mg/m2 IV, plus cisplatin 70mg/m2 IV Day 3: G-CSF SQ fr 5 cnsecutive days (days 3 thrugh 7). Repeat cycle every 15 days. Secnd-Line (Palliative) Chemtherapy fr Metastatic Disease Preferred Treatment: Single-agent taxane r gemcitabine Additinal Singe-Agent Treatment Optins: Cisplatin Carbplatin Dxrubicin 5-flururacil (5-FU) Ifsfamide Pemetrexed Methtrexate Vinblastine (Cancer Therapy Advisr) First-Line Radisensitising Chemtherapy Regimens Regimen: Cisplatin Cisplatin _ 5-FU 5-FU + mitmycin C Cisplatin + paclitaxel (Categry 2B) Lw-dse gemcitabine (Categry 2B) Dsing: Cisplatin 100mg/m2 IV every 2 weeks fr 3 cycles Days 1, 2, 3, 15, 16, and 17: IV hydratin at a rate f 500mL/hur; fllwed by 5-FU 400mg/m2 IV push; fllwed by cisplatin 15mg/m2 IV ver 1 hur as inductin and cnslidatin therapy Day 1 f raditherapy: Mitmycin 12mg/m2 IV blus, plus Week 1 (fractins 1 5) and Week 4 (fractins 16 20) f raditherapy: 5-FU 500mg/m2 cntinuus IV infusin (10 days ttal) Days 1, 8 and 15: Paclitaxel 50mg/m2 Days 1 3, 8 10, 15 17: Cisplatin 15mg/m2; fllwed by twice-daily raditherapy fr 8 days Gemcitabine 75mg/m2 IV weekly given cncurrently with raditherapy Nvember 2017 Page 15

16 (Cancer Therapy Advisr) Radisensitising Chemtherapy with Cnventinally Fractinated Radiatin Cisplatin Dcetaxel r paclitaxel (Categry 2B) 5-FU (Categry 2B) 5-FU and mitmycin C (Categry 2B) Capecitabine (Categry 3) Lw-dse gemcitabine (Categry 2B) (Cancer Therapy Advisr) Bilgic therapy - bilgic therapy is a treatment that uses the patient s immune system t fight cancer. Substances made by the bdy r made in a labratry are used t bst, direct, r restre the bdy s natural defences against cancer. This type f cancer treatment is als called bitherapy r immuntherapy. Chempreventin - chempreventin is the use f drugs, vitamins, r ther substances t reduce the risk f develping cancer r t reduce the risk that cancer will recur (cme back). Phtdynamic therapy - phtdynamic therapy (PDT) is a cancer treatment that uses a drug and a certain type f laser light t kill cancer cells. A drug that is nt active until it is expsed t light is injected int a vein. The drug cllects mre in cancer cells than in nrmal cells. Fibre-ptic tubes are then used t carry the laser light t the cancer cells, where the drug becmes active and kills the cells. Phtdynamic therapy causes little damage t healthy tissue. Immuntherapy - bladder cancer affects men mre likely than wmen with an estimated 77,000 new cases predicted t be diagnsed in 2016, and apprximately 16,000 deaths expected. Because f the recurrent nature f bladder cancer, patients with bladder cancer must mnitr their health clsely fr an extended perid f time. Immuntherapy has seen and cntinues t deliver prmising results in the treatment f bladder cancer - the first diagnsis fr which immuntherapy the Fd and Drug Administratin (FDA) granted apprval in Since last year, tw checkpint inhibitrs - atezlizumab and nivlumab - were als apprved fr bladder cancer, and there are numerus additinal immune-based treatments fr bladder cancer currently in develpment, with immuntherapy clinical trials fr bladder cancer patients n the rise. Bladder cancer immuntherapy has significantly reduced the risk f recurrence fr bladder cancer, while als increasing the percentage f patients wh see a cmplete respnse pstsurgery. Investigatinal bladder cancer immuntherapies - thse that "train" the bdy's immune system t recgnize bladder cancer cells - have the ptential t further imprve the general utcmes fr patients with this disease. Thanks t grundbreaking advancements in immunlgy research and clinical trials, immuntherapy has becme ne f the mst prmising bladder cancer treatments f ur time. Nvember 2017 Page 16

17 Currently, the verall 5-year survival rate fr bladder cancer is 77% - a rate which has nt changed significantly ver the last 10 years. Additinally, n new drugs fr bladder cancer were apprved by the FDA during this time. New and develping bladder cancer immuntherapies have the ptential t reduce recurrence rates and imprve survival rates fr patients with bladder cancer. Jin us as we wrk t change the future f bladder cancer treatment - frever. (Natinal Cancer Institute; May Clinic; Cancer Cuncil Victria; Cancer Research Institute). Changing f Lifestyle Fllwing Bladder Cancer Diagnsis Stp smking - Smking is a knwn risk factr fr many cancers. It is never t late t stp smking. Jin CANSA s e-kickbutt Prgramme r ask a dctr abut prgrammes t help stp smking. Fllw a nutritius diet - Eating a healthful diet may help avid ther medical cnditins linked t pr nutritin. Because cancer itself and sme cancer treatment may have a dulling effect n ne s appetite, it s imprtant that ne makes the mst f the calries taken in. Strngly cnsider cnsulting a registered dietitian (RD) t help learn mre abut the best kinds f fds t eat and hw t eat ther less healthful fds in mderatin. Eat five prtins f vegetables and fresh fruit (in seasn) every day. Rest when tired - The treatments fr cancer can add t the fatigue patients may experience. Fatigue is the mst frequently experienced symptm f cancer and cancer treatments. The fatigue can range frm just feeling tired t cmplete and utter exhaustin. It is imprtant t allw the bdy time t rest. This will help the bdy have the strength t heal itself. Studies have shwn a relatinship between fatigue and an increased mrbidity f cancer and cancer treatments as a result f fatigue's adverse effect n appetite, diminished quality f life, and lss f hpe. Seek supprt - The diagnsis f cancer is a life-defining event that is difficult t handle fr anyne. Facing the uncertainty f a serius disease, feeling anxius abut hw ne will feel during treatment, and wrrying abut the impact f bth the diagnsis and treatment can take a devastating tll that n ne shuld have t tackle n their wn. Try t have access t the fllwing: family friends religius cmmunity empathetic supprt grups fr peple with yur type f cancer prfessinal supprt (scial wrkers, psychlgists, and/r psychiatrists wh are trained t help supprt cancer patients and their families) Peple wh allw themselves t seek help while they are recvering frm cancer can ften maintain better emtinal equilibrium, which will help them face the challenges f cancer and its treatment (Winchester Hspital; Life is Beautiful). Abut Clinical Trials Nvember 2017 Page 17

18 Clinical trials are research studies that invlve peple. These studies test new ways t prevent, detect, diagnse, r treat diseases. Peple wh take part in cancer clinical trials have an pprtunity t cntribute t scientists knwledge abut cancer and t help in the develpment f imprved cancer treatments. They als receive state-f-the-art care frm cancer experts. Types f Clinical Trials Cancer clinical trials differ accrding t their primary purpse. They include the fllwing types: Treatment - these trials test the effectiveness f new treatments r new ways f using current treatments in peple wh have cancer. The treatments tested may include new drugs r new cmbinatins f currently used drugs, new surgery r radiatin therapy techniques, and vaccines r ther treatments that stimulate a persn s immune system t fight cancer. Cmbinatins f different treatment types may als be tested in these trials. Preventin - these trials test new interventins that may lwer the risk f develping certain types f cancer. Mst cancer preventin trials invlve healthy peple wh have nt had cancer; hwever, they ften nly include peple wh have a higher than average risk f develping a specific type f cancer. Sme cancer preventin trials invlve peple wh have had cancer in the past; these trials test interventins that may help prevent the return (recurrence) f the riginal cancer r reduce the chance f develping a new type f cancer Screening - these trials test new ways f finding cancer early. When cancer is fund early, it may be easier t treat and there may be a better chance f lng-term survival. Cancer screening trials usually invlve peple wh d nt have any signs r symptms f cancer. Hwever, participatin in these trials is ften limited t peple wh have a higher than average risk f develping a certain type f cancer because they have a family histry f that type f cancer r they have a histry f expsure t cancer-causing substances (e.g., cigarette smke). Diagnstic - these trials study new tests r prcedures that may help identify, r diagnse, cancer mre accurately. Diagnstic trials usually invlve peple wh have sme signs r symptms f cancer. Quality f life r supprtive care - these trials fcus n the cmfrt and quality f life f cancer patients and cancer survivrs. New ways t decrease the number r severity f side effects f cancer r its treatment are ften studied in these trials. Hw a specific type f cancer r its treatment affects a persn s everyday life may als be studied. Where Clinical Trials are Cnducted Cancer clinical trials take place in cities and twns in dctrs ffices, cancer centres and ther medical centres, cmmunity hspitals and clinics. A single trial may take place at ne r tw specialised medical centres nly r at hundreds f ffices, hspitals, and centres. Each clinical trial is managed by a research team that can include dctrs, nurses, research assistants, data analysts, and ther specialists. The research team wrks clsely with ther health prfessinals, including ther dctrs and nurses, labratry technicians, pharmacists, dieticians, and scial wrkers, t prvide medical and supprtive care t peple wh take part in a clinical trial. Nvember 2017 Page 18

19 Research Team The research team clsely mnitrs the health f peple taking part in the clinical trial and gives them specific instructins when necessary. T ensure the reliability f the trial s results, it is imprtant fr the participants t fllw the research team s instructins. The instructins may include keeping lgs r answering questinnaires. The research team may als seek t cntact the participants regularly after the trial ends t get updates n their health. Clinical Trial Prtcl Every clinical trial has a prtcl, r actin plan, that describes what will be dne in the trial, hw the trial will be cnducted, and why each part f the trial is necessary. The prtcl als includes guidelines fr wh can and cannt participate in the trial. These guidelines, called eligibility criteria, describe the characteristics that all interested peple must have befre they can take part in the trial. Eligibility criteria can include age, sex, medical histry, and current health status. Eligibility criteria fr cancer treatment trials ften include the type and stage f cancer, as well as the type(s) f cancer treatment already received. Enrlling peple wh have similar characteristics helps ensure that the utcme f a trial is due t the interventin being tested and nt t ther factrs. In this way, eligibility criteria help researchers btain the mst accurate and meaningful results pssible. Natinal and Internatinal Regulatins Natinal and internatinal regulatins and plicies have been develped t help ensure that research invlving peple is cnducted accrding t strict scientific and ethical principles. In these regulatins and plicies, peple wh participate in research are usually referred t as human subjects. Infrmed Cnsent Infrmed cnsent is a prcess thrugh which peple learn the imprtant facts abut a clinical trial t help them decide whether r nt t take part in it, and cntinue t learn new infrmatin abut the trial that helps them decide whether r nt t cntinue participating in it. During the first part f the infrmed cnsent prcess, peple are given detailed infrmatin abut a trial, including infrmatin abut the purpse f the trial, the tests and ther prcedures that will be required, and the pssible benefits and harms f taking part in the trial. Besides talking with a dctr r nurse, ptential trial participants are given a frm, called an infrmed cnsent frm, that prvides infrmatin abut the trial in writing. Peple wh agree t take part in the trial are asked t sign the frm. Hwever, signing this frm des nt mean that a persn must remain in the trial. Anyne can chse t leave a trial at any time either befre it starts r at any time during the trial r during the fllw-up perid. It is imprtant fr peple wh decide t leave a trial t get infrmatin frm the research team abut hw t leave the trial safely. The infrmed cnsent prcess cntinues thrughut a trial. If new benefits, risks, r side effects are discvered during the curse f a trial, the researchers must infrm the participants s they can decide whether r nt they want t cntinue t take part in the trial. In sme cases, participants wh want t cntinue t take part in a trial may be asked t sign a new infrmed cnsent frm. Nvember 2017 Page 19

20 New interventins are ften studied in a stepwise fashin, with each step representing a different phase in the clinical research prcess. The fllwing phases are used fr cancer treatment trials: Phases f a Clinical Trial Phase 0. These trials represent the earliest step in testing new treatments in humans. In a phase 0 trial, a very small dse f a chemical r bilgic agent is given t a small number f peple (apprximately 10-15) t gather preliminary infrmatin abut hw the agent is prcessed by the bdy (pharmackinetics) and hw the agent affects the bdy (pharmacdynamics). Because the agents are given in such small amunts, n infrmatin is btained abut their safety r effectiveness in treating cancer. Phase 0 trials are als called micr-dsing studies, explratry Investigatinal New Drug (IND) trials, r early phase I trials. The peple wh take part in these trials usually have advanced disease, and n knwn, effective treatment ptins are available t them. Phase I (als called phase 1). These trials are cnducted mainly t evaluate the safety f chemical r bilgic agents r ther types f interventins (e.g., a new radiatin therapy technique). They help determine the maximum dse that can be given safely (als knwn as the maximum tlerated dse) and whether an interventin causes harmful side effects. Phase I trials enrl small numbers f peple (20 r mre) wh have advanced cancer that cannt be treated effectively with standard (usual) treatments r fr which n standard treatment exists. Althugh evaluating the effectiveness f interventins is nt a primary gal f these trials, dctrs d lk fr evidence that the interventins might be useful as treatments. Phase II (als called phase 2). These trials test the effectiveness f interventins in peple wh have a specific type f cancer r related cancers. They als cntinue t lk at the safety f interventins. Phase II trials usually enrl fewer than 100 peple but may include as many as 300. The peple wh participate in phase II trials may r may nt have been treated previusly with standard therapy fr their type f cancer. If a persn has been treated previusly, their eligibility t participate in a specific trial may depend n the type and amunt f prir treatment they received. Althugh phase II trials can give sme indicatin f whether r nt an interventin wrks, they are almst never designed t shw whether an interventin is better than standard therapy. Phase III (als called phase 3). These trials cmpare the effectiveness f a new interventin, r new use f an existing interventin, with the current standard f care (usual treatment) fr a particular type f cancer. Phase III trials als examine hw the side effects f the new interventin cmpare with thse f the usual treatment. If the new interventin is mre effective than the usual treatment and/r is easier t tlerate, it may becme the new standard f care. Phase III trials usually invlve large grups f peple (100 t several thusand), wh are randmly assigned t ne f tw treatment grups, r trial arms : (1) a cntrl grup, in which everyne in the grup receives usual treatment fr their type f cancer, r 2) an investigatinal r experimental grup, in which everyne in the grup receives the new interventin r new use f an existing interventin. The trial participants are assigned t their Nvember 2017 Page 20