Standard of Care

From Standard of Care

Revision as of 20:23, 25 April 2012

Over 70,000 new cases diagnosed annually in the US, with about 14,000 deaths in the US.

The fourth most common neoplasm in males and eighth most common malignancy in females.

Worldwide frequency more than 350,000 new cases annually.

Males:females 4:1 with median age 73 years at diagnosis.

40% over the age of 70 years.

Incidence is increasing and represents the fourth most common cancer in the U.S.

Incidence rates in white individuals aged 50 years or more from 123.8-142.2 per 100,000 person years in men and from 32.5-33.2 per 100.000 person years in women, with similar patterns in other ethnic and racial groups.

Incidence is higher in industrialized countries rather than in developing nations.

Incidence increases with age.

First-degree relatives of patients with bladder cancer had at least a 50% greater risk of developing disease than the general population.

About 500,000 patients in the U.S. have a history of bladder cancer with a prevalence higher than lung cancer.

Because of frequent recurrences, requirement of intensive surveillance and frequent surgeries and long natural history of superficial tumors makes this lesion the most costly malignancy in the Medicare system from diagnosis to death.

A prostate stem cell antigen(PSCA) genetic variation raises commands risk of bladder cancer by 30-40%.

The PSCA gene missense variation rs 229-4008 raises the risk of bladder cancer.

Mortality per case is double that of prostate cancer and similar to breast cancer.

Annual incidence less than one-third of prostate cancer.

80% of newly diagnosed patients are 60 years or older.

Black patients are diagnosed at younger age than other patients.

Risk of diagnosis at an advanced stage increases by 1% per year of age and risk of death increased by 4%, 40% and 84% for older age, black and females, respectively.

Approximately 20% of bladder cancer patients die each year.

The median survival for patients with metastatic is 14 months, and this number has not significantly changed during the last two decades.

Mortality of all stages has stagnated at approximately 50%.

Most cases of cancer related death is the result of systemic disease rather than from the primary tumor.

Prognosis based on pathologic stage, tumor grade, tumor size, presence of associated carcinoma in situ, and multicentricity of lesions.

5-year disease specific survival after cystectomy 50-60%.

Squamous differentiation, perineural invasion and the presence of lymphovascular invasion impair prognosis.

Bladder neck tumors, and tumors within the prosthetic urethra, and those at the ureteral orifices are difficult to completely reset and to accurately stage.

Radical cystectomy should be offered two patients with adverse features such as flat lesions, diffusely infiltrating tumors, with involvement of the bladder neck, ureteral openings, and prostatic urethra.

85% present with hematuria.

Approximately 90% are transitional carcinomas.

One third of patients have smoking history.

Tobacco smoking is the best established risk factor for both men and women.

Causative factors: occupational exposure to chemicals such as aniline dyes, benzidine, xenylamine, cigarette smoking, analgesic abuse, bacterial and parasitic infections, pelvic irradiation, and chemotherapeutic agents such as cyclophosphamide.

Cystoscopy the gold standard for diagnosing bladder tumors.

70% present as a superficial tumor-Ta, T1 or Tis.

Early stage tumors classified in two groups: low grade tumors which are papillary and superficial and high grade tumors either papillary or nonpapillary and often invasive.

Superficial tumors are stages Ta, Tis, and T1 account for 75-85% of cancers while the remaining 15-25% are invasive T2, T3, and T4 or metastatic at the time of presentation.

20% patients present with invasive disease and 5% with metastases.

15-20% of patients will progress from non-muscle invasive to muscle-invasive disease.

50% of patients with invasive lesions succumb to the disease.

Approximately 30% of T1 patients treated by transurethral resection of the bladder (TURB) develop muscle invasive or higher stage bladder cancer.

Non-invasive tumors Ta, tumor in-situ, or T1 are treated with transurethral resection with or without intravesical instillation therapy, with recurrence rate as high as 50-70% and an average risk of 10-20% have progression to muscle invasive disease.

Approximately 20% of non-muscle invasive tumors are cured by surgery, while 50-70% recur one or more times without progressing to invasive disease and 10-30% progress to invasive and potentially lethal disease.

5-year all cause survival rate in patients with muscle invasion is 60-75%.

Time to progression to muscle invasion is unpredictable.

Lesions usually develop in the bladder neck and lateral walls.

Five times higher incidence of bladder cancer in hairdressers and a three times higher risk in women who use dark hair dye for more than 15 years.

The standard treatment for Ta and T1 disease is transurethral resection but 40-80% of patient's tumors recur within 12 months.

Transurethral resection with intravesical BCG provides a significantly better prophylaxis of tumor recurrence in Ta and T1 bladder cancer than transurethral resection alone.

Superficial disease Ta,T1, infiltrating disease T2-4, metastatic disease N+ or M+.

T1 is defined as tumor invading into the subepithelial connective tissue without evidence of invasion of the muscularis propia.

20-30% of tumors present as invasive carcinomas equal or greater than T1 stage.

Approximately 30% of T1 patients treated by transurethral resection of the bladder (TURB) develop muscle invasive or higher stage bladder cancer.

Histologic examination of specimens obtained by TURB suggest that 5-year progression free survival for patients with depth of invasion of less than 1.5 mm is 93%, compared with 67% for those with depth of invasion of equal or greater than 1.5 mm.

5-year survival for patients with cancer extending into perivesical fat when lymph node involvement is not present is 22%.

Almost no reports of bladder cancer as an incidental finding at autopsy studies indicating almost all bladder cancers are clinically sufficient to be diagnosed during life.

MRI and CT scans to evaluate lymph node metastases in the pelvis have low sensitivity of 0-30% for bladder cancer.

In a series of 507 cystectomy patients with a negative preoperative CT scan and a median of 22 lymph nodes removed a 24% of patients had nodal metastases (Madersbacher S).

Tis-as many as 20% with diffuse involvement have muscle invasion and about 10% with focal involvement have occult regional lymph node metastases.

70% present initially as superficial tumors and their risk of progression to muscle invasion is low at 5-10%.

Low grade tumors rarely progress (approximately 2% progression rate) and remain confined the (mucosa stage Ta).

On going surveillance is required after diagnosis and treatment of early stage disease with repeated cystoscopy and urinary cytology and regular local resections are often needed to control recurrent disease.

Transurethral resection with surveillance cystoscopy is sufficient treatment for most low grade noninvasive tumors.

While most patients with low-grade noninvasive tumors will recur within five years that they will rarely invade or result in death.

A single administration of perioperative intravesicle chemotherapy reduces the risk of recurrence in non-muscle invasive disease treated with transurethral resection.

No single agent given in the perioperative period by intravesicle administration is superior in preventing recurrence of low grade noninvasive tumors.

Perioperative intravesicle chemotherapy is associated with a 10 to 15% reduction in recurrence rates in low grade non-muscle invasive disease.

High risk patients with non-muscle invasive bladder cancer include patients with high-grade disease, and patients with carcinoma in situ and include patients with lesions greater than 3 cm, multifocal tumors, lamina propria invasion and with recurrence within two years.

In patients with high risk non-muscle invasive bladder disease intervention with intravesicle therapy leads to response rates up to 85%, with recurrence rates of more than 50% within the first year and 90% by five years.

In patients with high-risk non-muscle invasive bladder cancers have a 50% progression to muscle invasive disease despite intravesicle therapy.

Flat or diffusely infiltrating bladder tumors have a twofold increase progression risk compared to papillary bladder lesions.

Most deaths due to bladder cancer may be attributed to muscle invasive, high-grade stages T2 or greater disease.

At initial diagnosis almost 50% of patients with high-grade bladder cancer have muscle invasive disease.

30% of those patients with initial low-grade tumor have a higher grade recurrence.

BCG can effectively treat patients with residual superficial cancers with a 60% response rate.

Intravesical bacillus Calmette-Guerin is the main treatment for carcinoma in situ or high grade superficial bladder carcinoma.

Radical cystectomy standard treatment for muscle invasive bladder carcinoma with 5-year survival rates for all stages 48-66%, indicating that the majority of patients with high grade invasive disease die of metastases within 3 years.

Radical cystectomy primary treatment for localized or regionally advanced bladder cancer, as well as high risk superficial tumors that are resistant to intravesical therapy.

Radical cystectomy involves removal of the bladder and seminal vesicles in men, and removal of the bladder, uterus, fallopian tubes, ovaries, and a segment of the anterior vaginal wall in females.

Following radical cystectomy colon is utilized for reconstruction to store and empty urine.

Radical cystectomy last between 4-10 hours, an in the hospital stay ranging between 5-10 days, and is associated with postoperative complications including atelectasis, ileus, and wound infections.

Patients with orthotopic neobladder following cystectomy have higher rates of complications including incontinence bowel and sexual function impairment is then patients who can have a bladder preserved (Gilbert SM).

5 year overall survival rates for patients treated with cystectomy or a more conservative approach with similar clinical staging is about 50%.

Of patients that present with muscle invasive disease 50% have distant metastases within 2 years, and 60% die within 5 years.

Typically 30-80% of patients who have a bladder cancer have another lesion within 3 years after treatment of the initial tumor.

Bladder cancer-superficial tumors treated transurethrally 50%-75% recur.

5-year survival for patients with positive nodal disease at radical cystectomy ranges from 5-30%.

Median survival for patients with unresectable disease 7-20 months.

For locally advanced disease chemotherapy is the standard treatment and despite 50% response rate the cure rate is less than 10%.

Elderly patients treated with radical cystectomy have higher pathological stage and poorer relapse-free survival than younger patients

Telomerase activity detected in almost all superficial urothelial cell cancers but not in healthy urothelial cells.

Methotrexate, vinblastine, doxorubicin, and cyclophosphamide (MVAC) vs gemcitabine and cisplatin (GC) in advanced disease: 405 patients similar response rates and survival 14.8 months vs 13.8 months, respectively (von der Masse H et al).

In the above study GC better safety profile and tolerability, and is presently standard treatment for metastatic disease (2010).

Neoadjuvant chemotherapy in muscle invasive bladder cancer-comparing local radical treatment alone vs local radical treatment alone preceded by three cyles of neoadjuvant cisplatin, methotrexate and vinblastine: 16% reduction in the risk of death, correspondinig to an increase in 10 year survival from 30% to 36% (International Trialists Phase III trial Assessing Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer).

Neoadjuvant chemotherapy followed by definitive local therapy is presently the state of the art for deeply invasive bladder cancer, compared with suspect in me or radiotherapy alone.