1. WELCOME

2. Presented by: Ms. Krantee More.
Bladder Cancer
Presented by: Ms. Krantee More.

3. INTRODUCTION GENERAL OBJECTIVE:
To gain in depth knowledge regarding CANCER OF URINARY BLADDER.

4. SPECIFIC OBJECTIVES: SPECIFIC OBJECTIVES:
After completing the seminar students will be able to:
Enumerate the etiological factors of urinary bladder cancer (ca. bladder),
Illustrate clinical manifestations.
Describe the management of Ca bladder
To enlist the complications occurring due to same disease

5. DEFINATION
Bladder cancer is a cancerous tumor in the bladder -- the organ that holds urine

6. Epidemiology of Bladder CA
4th most common CA in men, 9th in women,
Annual New Cases = 68,810 (51,230 in M & 17,580 in F)
M:F = 3:1
Annual Deaths = 14,100 (7,750 in M & 4,150 in F)
Other Urothelial Tumors - 8% originiate in the renal pelvis, and the remaining 2% in the ureter and urethra.

7. Risk Factors for Bladder CA
Age, Gender, Race
Cigarette smoking (2-4x higher relative risk)
Exposures to environmental carcinogens:
Occupational - Polycyclic aromatic hydrocarbons,benzene, exhaust from combustion gases, aryl amines
dry cleaners; manufacturers of preservatives, dye, rubber, & leather; pesticide applicators; painters; truck drivers; hairdressers; printers; machinists
Pelvic radiation therapy
Arsenic (eg. in drinking H2O)
Cigarette smoking - #1 avoidable risk factor
Some carcinogens in tobacco smoke are absorbed from lungs and get into blood. From there, they are filtered by kidneys and concentrated in urine. These chemicals in the urine damage the urothelial cells that line the inside of the bladder  inc’d CA risk.

8. Risk Factors for Bladder CA
Infections
Schistosoma haematobium (N Africa)  Inc’d risk for squamous & transitional cell CAR
Chronic UTIs, chronic bladder stones, indwelling Foleys  inc’d risk for squamous cell CAR
Other
Prior h/o bladder CA
Low fluid intake (inc’d exposure to carcinogens via dec’d bladder emptying)
Genetics (eg, Retinoblastoma gene)
Bladder birth defects (eg, persistent urachus)  inc’d risk for adenocarcinoma.
Schistosoma haematobium  formation of carcinogenic N-nitroso compounds  increased risk for both squamous and transitional cell CAR
Cyclophosphamide and Ifosfamide (d/t acorlein, a uirnary metabolite of this medication)  9 fold inc’d risk (dec’d w/ Mesna d/t dec’d bladder irritation)
Urachus = connection b/w belly button and bladder. Normally disappears before birth. If part of the connection remains, it could become cancerous. Cancers that start in the urachus are usually made up of malignant gland cells and are called adenocarcinomas.

9. ANATOMY AND PHYSIOLOGY

10. Pathophysiology

11. Clinical Manifestations of Bladder CA
Hematuria (80-90%) – Generally painless and gross hematuria
However, 20% can have only microscopic hematuria
Other urinary Sxs
Frequency, urgency, nocturia – d/t irritative Sxs or dec’d bladder capacity
Pain (less common & often reflects tumor location)
Lower abdominal pain – Bladder mass
Rectal discomfort & perineal pain – Invasion of prostate or pelvis.
Flank pain - Obstruction of ureters
The bladder is the MC source of gross hematuria (40%), but benign cystitis (22%) is a more common cause than bladder CA (15%). Microscopic hematuria is more commonly of prostate origin (25%); only 2% of bladder CAs produce microscopic hematuria.

12. Continue… Lower extremity edema from iliac vessel compression,
Physical: occasionally an abdominal or pelvic mass may be palpable.

13. Dx of Bladder CA Pts w/ hematuria, especially if > 40 yrs
Urinary Cytology- microscopy, culture to rule out infection,
USG- abdomen & pelvis,
CT abdomen & pelvis with preinfusion & post infusion phases,
Cystoscopy, regardless of cytology results (mainstay of dx)
Screening of aSx’c pts not recommended (dx’d at an earlier stage but no proven survival benefit)

14. Continue..
Retrograde pyelography in patients in whom contrast CT scan can’t be performed because of azotemia or due to severe allergy to IV contrast,
Transurethral resection of all visible tumors to determine histology & depth of invasion
Biopsies of erythematous (& possibly normal) areas to assess for CIS

15. STAGES
Stage 0 -- Non-invasive tumors that are only in the bladder lining
*Stage I -- Tumor goes through the bladder lining, but does not reach the muscle layer of the bladder
*Stage II -- Tumor goes into the muscle layer of the bladder
*Stage III -- Tumor goes past the muscle layer into tissue surrounding the bladder
*Stage IV -- Tumor has spread to neighboring lymph nodes or to distant sites (metastatic disease)
Stage V--*Prostate 2)Rectum 3)Ureters 4)Uterus 5)Vagina 6)Bones 7)Liver 8)Lungs

16. Treatment: Medical (Ta, T1, CIS): non muscle invasive
Intravesical immunotherapy:
Indications
Adjuvant tx w/ resection to prevent recurrence
Eliminate disease that cannot be controlled by endoscopic resection alone (less common)
Recurrent disease, > 40% involvement of bladder surface, diffuse CIS, T1 dz
Generally not needed for solitary papillary lesions
Intravesical therapy is not used for muscle-invasive tumors b/c these agents do not penetrate beyond a few layers of cells.
BCG is highly effective in eradicating Tis, with 70% of patients being disease free at 1 year and 40% at 10 years.

17. Continue.. Agents Std agent -- BCG
Generally 6 weekly txs then monthly maintenance x 1-3 yrs
Toxicities = Bladder irritability / spasm, hematuria, dysuria, & rarely systemic TB
Other agents – Mitomycin-C, Interferon, Gemcitabine

18. For muscle invasive disease (T2 & greater)
Neo-adjuvant chemo x 12 wks prior to cystectomy
Inc’d 5-yr dz-free survival
MVAC (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) – 3 cycles q 28 days

19. Surgical Rx: For Ta, T1, CIS (non muscle invasive)
1. Endoscopic treatment:
TURBT- To dignose, to stage, to treat visible tumors.
Electrocautry or LASER fulguration of bladder is sufficient for low grade, small volume tumors.
2. Radical cystectomy:
Patients withunresectable, prostatic urethra involvement & BCG failure are indications for this procedure.

20. Muscle invasive disease: T2 & greater
1. Radical cystoprostectomy: (men)
Remove the bladder, prostate & pelvic lymph nodes.
After removal of bladder, urinary diversion must be created.
Types:
Continent,
Incontinent.

21. Tx & Prognosis of Bladder CA – Muscle-Invasive Dz – Mgmt of Urine Flow
Conduit Diversion
Urine is drained from the ureters to a loop of small bowel anastomosed to the abdominal skin surface. It is then collected in an external appliance. Currently uncommonly used.
Continent Cutaneous Reservoir
Created from a detubularized segment of bowel attached to the abdominal wall w/ a continent stoma that can be regularly self-cath’d.
 Continence in 65–85% of men at night and 85–90% of men during the day.
Orthotopic Neobladder
Low-pressure reservoirs anastomosed to the urethra  more natural drainage, as pts can void via the urethra.
CI’s = Renal insuff, inability to self-catheterize, or an exophytic tumor or CIS in the urethra.
Re Neobladder - Diffuse CIS in the bladder is a relative contraindication based on the risk of a urethral recurrence. Concurrent ulcerative colitis or Crohn's disease may hinder the use of resected bowel.

22. Tx & Prognosis of Bladder CA – Muscle-Invasive Dz
Sometimes bladder sparing approach is used (~ 5-10% are candidates)
Complete endoscopic resection; partial cystectomy; or combination of resection, chemo, and radiation
Considered when dz is limited to the bladder dome,  2 cm can be achieved, no CIS in other sites, & bladder capacity adequate after tumor removal.
Muscle-Invasive Tumors
For tumors infiltrating the muscularis propria, the standard of care in the United States is radical cystectomy and pelvic lymphadenectomy because of the high likelihood of cancer extending into perivesicular fat or into regional lymph nodes; improved survival and decreased local recurrence are associated with an increased number of regional lymph nodes removed. This approach provides 5-year disease-free survival in 75 to 80% of patients with organ-confined disease, in approximately 50% of patients with tumors extending into the perivesical tissues, and in nearly a third of patients with regional lymph node involvement. Prostatectomy is also performed in men; in women, the urethra, uterus, fallopian tubes, ovaries, and anterior vaginal wall are removed. Urinary flow can be directed through either a conduit diversion or a continent reservoir. With a conduit diversion, urine is drained directly from the ureters to a loop of small bowel that is anastomosed to the skin surface with no internal reservoir; urine is collected in an external appliance. Alternatively, a low-pressure continent reservoir can be created from a detubularized segment of bowel attached to the abdominal wall with a continent stoma that can be self-catheterized at regular intervals; low-pressure reservoirs can also be anastomosed to the urethra, thereby creating an internal orthotopic neobladder and permitting the patient to void via the urethra. Complications of cystectomy include recurrent urinary infections, hyperchloremic acidosis, oxalate stones, incontinence, and impotence.
Neoadjuvant chemotherapy for 12 weeks before cystectomy improves 5-year disease-free survival. Neoadjuvant chemotherapy with the four-drug regimen MVAC (methotrexate, 30 mg/m2 on days 1 and 15; vinblastine, 3 mg/m2 on days 2 and 15; doxorubicin, 30 mg/m2 on day 2; and cisplatin, 70 mg/m2 on day 2, all given for three cycles every 28 days) improves median survival from 46 months to 77 months compared with surgery alone.[5] This therapy requires normal renal function and good performance status.
Patients with a solitary early-stage lesion and no evidence of hydronephrosis can be treated with simultaneous chemotherapy (usually cisplatin) and 65 Gy of radiation delivered in five daily fractions a week ranging from 2.0 to 2.5 Gy rather than cystectomy after successful, nearly complete transurethral resection of the tumor. Toxicities include inflammation of the skin, impotence, fatigue, and irritative symptoms from the bladder and bowel; persistent proctitis is rare. The 5-year disease-free survival rate with this approach is 50%, with the majority of patients retaining a normally functioning bladder.
Metastatic Disease
For patients with metastatic disease, the two most commonly used regimens are gemcitabine (1000 mg/m2 on days 1, 8, and 15) plus cisplatin (70 mg/m2 on day 2) (referred to as GC), recycled every 28 days, and the four-drug regimen of MVAC (doses and schedule as noted earlier); both regimens are given for a total of six cycles of therapy over a 6-month period. The most frequently observed toxicities include anemia, thrombocytopenia, neutropenic fever, mucositis, and fatigue. The two-drug GC regimen is better tolerated and has less severe toxicities; both regimens provide a median survival of approximately 14 months and a 5-year survival rate of about 15%.[6] Patients with good performance status and metastatic disease limited to the lymph nodes have a 20 to 33% 5-year disease-free survival rate.
Invasive Disease
The probability of recurrence following surgery is predicted on the basis of pathologic stage, presence or absence of lymphatic or vascular invasion, and nodal spread. Among those whose cancers recur, the recurrence develops in a median of 1 year (range 0.04–11.1 years). Long-term outcomes vary by pathologic stage and histology (Table 90-1). The number of lymph nodes removed is also prognostic, whether or not the nodes contained tumor.
Table 90-1 Survival Following Surgery for Bladder CancerChemotherapy (described below) has been shown to prolong the survival of patients with invasive disease, but only when combined with definitive treatment of the bladder by radical cystectomy or radiation therapy. Thus, for the majority of patients, chemotherapy alone is inadequate to clear the bladder of disease. Experimental studies are evaluating bladder preservation strategies by combining chemotherapy and radiation therapy in patients whose tumors were endoscopically removed.
The primary goal of treatment for metastatic disease is to achieve complete remission with chemotherapy alone or with a combined-modality approach of chemotherapy followed by surgical resection of residual disease, as is done routinely for the treatment of germ cell tumors. One can define a goal in terms of cure or palliation on the basis of the probability of achieving a complete response to chemotherapy using prognostic factors, such as Karnofsky Performance Status (KPS) (<80%), and whether the pattern of spread is nodal or visceral (liver, lung, or bone). For those with zero, one, or two risk factors, the probability of complete remission is 38, 25, and 5%, respectively, and median survival is 33, 13.4, and 9.3 months, respectively. Patients who are functionally compromised or who have visceral disease or bone metastases rarely achieve long-term survival. The toxicities also vary as a function of risk, and treatment-related mortality rates are as high as 3–4% using some combinations in these poor-risk patient groups.
Chemotherapy
A number of chemotherapeutic drugs have shown activity as single agents; cisplatin, paclitaxel, and gemcitabine are considered most active. Standard therapy consists of two-, three-, or four-drug combinations. Overall response rates of >50% have been reported using combinations such as methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC); cisplatin and paclitaxel (PT); gemcitabine and cisplatin (GC); or gemcitabine, paclitaxel, and cisplatin (GTC). M-VAC was considered standard, but the toxicities of neutropenia and fever, mucositis, diminished renal and auditory function, and peripheral neuropathy led to the development of alternative regimens. At present, GC is used more commonly than M-VAC, based on the results of a comparative trial of M-VAC versus GC that showed less neutropenia and fever, and less mucositis for the GC regimen. Anemia and thrombocytopenia were more common with GC. GTC is not more effective than GC.
Chemotherapy has also been evaluated in the neoadjuvant and adjuvant settings. In a randomized trial, patients receiving three cycles of neoadjuvant M-VAC followed by cystectomy had a significantly better median (6.2 years) and 5-year survival (57%) compared to cystectomy alone (median survival 3.8 years; 5-year survival 42%). Similar results were obtained in an international study of three cycles of cisplatin, methotrexate, and vinblastine (CMV) followed by either radical cystectomy or radiation therapy. The decision to administer adjuvant therapy is based on the risk of recurrence after cystectomy. Indications for adjuvant chemotherapy include the presence of nodal disease, extravesical tumor extension, or vascular invasion in the resected specimen. Another study of adjuvant therapy found that four cycles of CMV delayed recurrence, although an effect on survival was less clear. Additional trials are studying taxane- and gemcitabine-based combinations.
The management of bladder cancer is summarized in Table 90-2.
Table 90-1 Survival Following Surgery for Bladder CancerPathologic Stage5-Year Survival, %10-Year Survival, %T2,N08987T3a,N07876T3b,N06261T4,N05045Any T,N13534
Table 90-2 Management of Bladder CancerNature of LesionManagement ApproachSuperficialEndoscopic removal, usually with intravesical therapyInvasive diseaseCystectomy ± systemic chemotherapy (before or after surgery)Metastatic diseaseCurative or palliative chemotherapy (based on prognostic factors) ± surgery
Treatment
Management of bladder carcinoma depends on tumor stage. The TNM system is recommended for staging. For most superficial bladder carcinomas, transurethral resection of the tumor is often the only treatment required. However, for CIS or high-grade superficial tumors, tumors that involve the lamina propria (stage T1), and rapidly recurrent tumors, treatment with intravesical agents such as thiotepa (Thioplex), doxorubicin (Adriamycin), and mitomycin C (Mutamycin)[1] or intravesical bacillus Calmette-Guérin (BCG, Tice) may be indicated.
Treatment depends on tumor stage.   
▪   
Superficial bladder (Ta) cancers are managed with transurethral resection.
CIS or high-grade stage Ta, tumors that involve the lamina propria (stage T1), and recurrent tumors are managed with transurethral resection and intravesical therapy such as thiotepa (Thioplex), doxorubicin (Adriamycin), and mitomycin C (Mutamycin)[1] or intravesical bacillus Calmette-Guérin (BCG, Tice).
Bladder surveillance is mandatory because the recurrence rate in the bladder may be as high as 50% at 5 years.
Surveillance protocols include cystoscopy and urinary cytologic examinations every 3 months for the first year, every 4 months for the second year, semiannually in year 3, and annually thereafter.
Periodic evaluation of the upper tracts should be performed as well.
In superficial tumors that progress in stage or fail conservative therapy and in those that invade the bladder muscle (stages T2-3), a radical cystectomy and urinary diversion is the treatment of choice.
Urinary diversion may be either incontinent (conduit) or continent (orthotopic or continent cutaneous).
Five-year survival rates are 85%–60% after cystectomy for stages T2a and T2b, respectively. For stage T3a and T3b tumors, the 5-year survival decreases to 60% and 40%, respectively, whereas patients with node-positive disease have a 5-year survival of <30%.
Patients with T2–T4 disease may be offered either neoadjuvant or adjuvant chemotherapy. There have been reports of modest survival advantages (<10%) using MVAC in the neoadjuvant setting.
Patients with M1 disease are generally treated with chemotherapy as well.
The standard regimen over the past decade has been methotrexate (Trexall),[1] vinblastine (Velban),[1] doxorubicin (Adriamycin), and cisplatin (Platinol) (MVAC); however, durable complete response rates are <15%.
Newer agents such as gemcitabine (Gemzar) along with cisplatin appear to offer similar response rates and reduced toxicity.

23. Tx & Prognosis of Bladder CA – Metastatic Dz
2 Main Regimens (Gemcitabine + Cisplatin OR MVAC)
6 cycles over 6 mos
GC is often better tolerated.
Both  5 yr survival rate of ~ 15% (20-33% if good performance status and mets confined to LNs), w/ median survival of ~ 14 mos.

24. 2. Radiation therapy: External beam radiation therapy has been shown to be inferior to radical cystectomy.

25. Complications: Body image disturbances, Skin irritation, Recurrence,
Infertility in women as uterus is removed,
Infertility in men if prostate is removed,
Menopause if ovaries are removed,
Sexual disturbances if vagina has been made shorter,
Metastasis to distant organs.

26. Nursing Diagnosis: Dysurea related to disease condition,
Disturbed sleep pattern due to urgency & frequency of micturition,
Acute pain related to disease condition,
Altered nutrition secondary to pain due to disease condition,
Anxiety related to surgery,
Disturbed body image related to surgery.

27. Research evidence:
A research carried out by “Yursh Xia 4th military medical university” states that, “Adjuvant Radiotherapy in addition to cystectomy also increases survival rates.”
A research by “Dept of Urology Health Science, Centre West Virginia Morgan Town” says that “Garlic can be used an immunotherapy besides BCG.”

28. SUMMARY

29. CONCLUSION

30. References

31. Harrison’s Internal Medicine
Cecil Textbook of Medicine
Cancer: Principles & Practice of Oncology
National Cancer Institute website
American Cancer Society website

36. THANK YOU