Background : Staging : Treatments : Radiotherapy

BACKGROUND:

Epidemiology:

Approximately 55,000 new cases of bladder cancer are diagnosed each year.  The peak incidence occurs in the seventh decade of life with a male/female ratio of 3:1.  Bladder cancer is the fourth most prevalent malignant disease in men.  The prevalence is higher in industrialized nations and urban areas.

Risk factors for the development of bladder cancer include: Occupational exposures to dye, rubber, leather, paint, organic chemicals, textile printing, electrical cable industries, cigarette smoking, phenacetin containing analgesics, chronic irritation by long term catheter drainage for bladder calculi, and chronic infections.  Transitional cell carcinomas, the most common pathologic type account for 92 percent of cancers.  Squamous cell carcinomas account for 6 percent, and adenocarcinomas for 2 percent.

Of newly diagnosed bladder cancers, approximately 75 - 85 percent are superficial, and 15 - 25 percent have evidence of muscle invasion. 

The bladder trigone, lateral and posterior walls, and bladder neck are the most common sites of tumor development. The most common sites of distant metastasis include the lung, bone, and liver.

SIGNS & SYMPTOMS:

The most common symptom experienced is gross, painless, hematuria.  Less commonly, patients experience bladder irritability.  A small percentage have no specific symptoms or microscopic hematuria.

DIAGNOSTIC TESTS:

A complete history and physical examination including directed pelvic and rectal examination should always be included in any workup.  Additionally, laboratory work including blood cell count, liver function test, and urinalysis should be obtained.  If a bladder tumor is suspected, urine cytology can also be obtained at this time. Cystoscopy and biopsy ultimately lead to diagnosis and provide staging information. 

Once a pathologic diagnosis of bladder cancer has been obtained, further tests are used for staging.  CT scans of the abdomen and pelvis, chest x-ray, and bone scan are used to evaluate the extensiveness of the cancer within the pelvis as well as to look for areas of distant spread. 

STAGING:

The AJCC staging system for bladder cancer makes use of information of the primary tumor, original lymph nodes, and distant metastatic disease. 

PRIMARY TUMOR:

TX - the primary tumor can not be assessed;

T0 - no evidence of primary tumor;

Ta - non-invasive papillary carcinoma;

TIS - carcinoma in situ;

T1 - tumor invades the subepithelial connective tissue;

T2a - tumor invades the superficial muscles;

T2b - tumor invades the deep muscle;

T3a - tumor invades the perivesical tissue microscopically;

T3b - tumor invades the perivesical tissue macroscopically;

T4a - tumor invades the prostate, uterus, or vagina;

T4b - tumor invades the pelvic wall or abdominal wall.

REGIONAL LYMPH NODES:

NX - regional lymph nodes can not be assessed;

N0 - no regional lymph node metastases;

N1 - metastases in a single lymph node, 2 cm or less in greatest dimension;

N2 - metastases in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension;

N3 - metastases in a lymph node more than 5 cm in greatest dimension.

DISTANT METASTASES:

MX - distant metastases can not be assessed;

M0 - no distant metastases;

M1 - distant metastases.

STAGE GROUPING:

Stage 0a, Ta -  N0 M0;

Stage 0is, Tis - N0 M0;

Stage I - T1 N0 M0;

Stage II - T2a or T2b N0 M0;

Stage III - T3a, T3b, T4a N0 M0;<

Stage IV - T4b N0 M0, NET N1, 2, or 3, M0, or NET, NEN, M1.

TREATMENT OPTIONS:

SUPERFICIAL BLADDER CANCERS:

The primary treatment includes a transurethral resection of the bladder tumor.  In some cases, intravesicular treatment with BCG or other chemotherapy agents is used to help decrease the risk of local recurrence. 

Cystectomy, or complete removal of the bladder, is reserved for patients with multiple tumors, multiple recurrences, or a poorly functioning bladder.

MUSCLE INVADING BLADDER CANCERS:

Non-Bladder Sparing Treatment:

Non-bladder sparing treatment consists of a radical cystectomy.  This is indicated when patients are non-amenable to a partial resection, have a poorly functioning bladder, have high-grade disease associated with Tis, or have multicentric or frequent recurrence of low-grade disease.  In some instances, preoperative (or postoperative) radiotherapy is used.  There is no clear role for the adjuvant use of chemotherapy. 

Bladder Sparing Treatment:

Bladder sparing treatment includes surgical and nonsurgical approaches.  Partial cystectomy is indicated for a solitary tumor located in the dome of the bladder so that adequate margins can be obtained.  There is no previous history of transitional cell carcinoma, there is no associated carcinoma in situ, and there is normal bladder functioning.  Transurethral bladder tumor resections with and without postoperative radiotherapy could be considered as well.  There is very limited data on this type of treatment.  Alternatively, the use of radiotherapy alone, chemotherapy alone, or a combination of the two has been used.  The most promising results have been obtained with combined modality therapy consisting of chemotherapy and radiotherapy after maximal transurethral resection of the tumor.  Four prospective randomized trials have shown survival rates equivalent to that of cystectomy.  Of those who did well with the treatment, the majority maintained an adequately functioning bladder.  For patients with metastatic disease both chemotherapy and palliative radiation can be used for treatment.  Radiation offers very good palliation of bleeding and pain.

RADIOTHERAPY PROCEDURES:

External Beam Radiotherapy - This treatment requires a planning session to be performed prior to beginning treatment.  The planning session is performed in our treatment planning simulator room.  A bladder catheter and rectal catheter are temporarily inserted and contrast material is instilled.  X-rays are taken of the pelvic area.  A CT scan is also performed.  Once complete, the catheters are removed and the patient is sent home.  The treatment planning technique used is called 3D conformal radiation.  The CAT scan images are transferred to the treatment planning computer, and the tumor volume a well as normal tissue structures are drawn on each of the CAT scan images. The physician and Dosimetrist then work together to generate a treatment plan.  Once this is complete, treatments can be initiated.  On the first day of treatment, a block check is performed to make sure that what was planned on the computer matches what will be performed on the patient.  Radiation treatments are given Monday through Friday, once a day, five days per week.  Each treatment takes approximately 15 to 20 minutes to deliver.  The treatment course for bladder cancer is approximately 7 weeks. 

Interstitial Irradiation - This type of treatment for bladder cancer is used less frequently.  It entails the placement of catheters directly into the wall of the bladder where the tumor is located.  This is performed in the operating room with the aid of the urologist.  The catheters are loaded with radiation sources at a later time.  Once an adequate amount of radiation has been delivered, the sources of radiation and catheters are removed.

Intracavitary Irradiation - This form of treatment is rarely used.  This treatment entails placement of radiation sources directly into the bladder itself.  Again, the placement of the sources is for specified time. 

RADIATION SIDE EFFECTS:

Acute Side Effects: These side effects happen during radiation and go away once radiation has been completed.  They include: urinary frequency, urgency, hesitancy, dysuria, decreased force of urinary stream, diarrhea, and fatigue.  There are medications available for the majority of these side effects.  Late Side Effects: These side effects happen anywhere from 6 months to a few years following completion of radiation.  They are rare, but can cause permanent problems.  These include injury to the bladder itself, rectum, or small intestines.

FOLLOW-UP:

Follow-up is performed with routine history and physical examination, cystoscopy and urine cytology every 3 months for 2 years, then every 6 months thereafter, and CT scans.

Larry N. Silverman, M.D.