Cancer information Cancer treatment

Cervical Cancer

Carcinoma of the cervix continues to occur, although the incidence is clearly decreasing; what we are talking about are predominantly squamous cell carcinomas which are the most common variety, accounting for approximately 80% of all cervical cancers, adenocarcinoma represents approximately 20%, other cell types are much less common. There are currently approximately 14,000 cases a year, and the clinical spectrum is changing, cervical carcinoma has traditionally been a big topic in gynecology for understandable reasons, it is still important for us as gynecologists to be leaders in this field in our ability to recognize the disease and suggest appropriate treatment.

At the present time in the United States, approximately one-half of the cases of invasive carcinoma of the cervix are advanced at the time of diagnosis. What is the cause of death? It is either uncontrolled disease in the pelvis, or distant metastasis and I will come back to these issues. The pattern of spread is something you are familiar with, and something we want to keep in mind when we talk about treatment. There is first of all, local expansion in the pelvis, lymphatic spread through the regional and more distant lymph nodes, hematogenous spread is of importance predominantly in the late stages of the disease. What are the symptoms of cervical carcinoma? As a reminder, patient’s traditionally present with either abnormal vaginal bleeding or discharge. I want to share with you that not recognizing this continues to occur, and is not infrequently a cause or a reason for not timely diagnosing sometimes advanced cervical carcinoma. Most of the symptoms, are symptoms of advanced disease, pain, typical lumbosacral pain, pain in the gluteal area, hematuria, rectal bleeding. A lot of patient’s with cervical cancer of course, will have no symptoms because the disease will be diagnosed in the workup of an abnormal PAP smear.

The diagnosis typically relies on the biopsy of any gross lesion of the cervix. Workup of an abnormal PAP smear in a number of cases will lead to the diagnosis of an invasive cancer of the cervix, and this will include colposcopy and biopsy or cone biopsy. As a reminder, the cervix is grossly abnormal as in this case, the first thing to do is to biopsy here, this lesion is not approached by doing a PAP smear, and again, maybe with decreasing incidents of cervical cancer and the fact that we are more adapt in working up abnormal PAP smears and doing colposcopy, one needs to be reminded of the fact that lesions such as these need to be biopsied, and the answer will be obvious.

Bladder Cancer. Treatment

A. Intravesical Chemotherapy: Immuno- or chemotherapeutic agents can be delivered directly into the bladder by a urethral catheter. They can be used to eradicate existing disease or to reduce the likelihood of recurrence in those who have undergone complete transurethral resection. Such therapy is more effective in the latter situation. Most agents are administered weekly for 6–12 weeks. The use of maintenance therapy after the initial induction regimen may be beneficial. Efficacy may be increased by prolonging contact time to 2 hours. Common agents include thiotepa, mitomycin, doxorubicin, and BCG, the latter being the most effective agent when compared with the others. Side effects of intravesical chemotherapy include irritative voiding symptoms and hemorrhagic cystitis. Systemic effects are rare. Patients who develop symptoms from BCG may require antituberculous therapy.

B. Surgical Treatment: Although transurethral resection is the initial form of treatment for all bladder cancers as it is diagnostic, allows for proper staging, and will control superficial cancers, muscle infiltrating cancers will require more aggressive treatment. Partial cystectomy may be indicated in patients with solitary lesions and those with cancers in a bladder diverticulum. Radical cystectomy entails removal of the bladder, prostate, seminal vesicles, and surrounding fat and peritoneal attachments in men and in women also the uterus, cervix, urethra, anterior vaginal vault, and usually the ovaries. Bilateral pelvic lymph node dissection is performed simultaneously.

Urinary diversion can be performed using a conduit of small or large bowel. However, continent forms of diversion have been developed that avoid the necessity of an external appliance.

C. Radiotherapy: External beam radiotherapy delivered in fractions over a 6- to 8-week period is generally well tolerated, but approximately 10–15% of patients will develop bladder, bowel, or rectal complications. Unfortunately, local recurrence is common after radiotherapy (30–70%). Increasingly, radiotherapy is being combined with systemic chemotherapy in an effort to improve local and distant relapse rates.

D. Chemotherapy: Fifteen percent of patients with newly diagnosed bladder cancer will present with metastatic disease, and 40% of those thought to have localized disease at the time of cystectomy or definitive radiotherapy will develop metastases usually within 2 years after the start of treatment. Cisplatin-based combination chemotherapy will result in partial or complete responses in 15–35% and 15–45% of patients, respectively.

Combination chemotherapy has been integrated into trials of surgery and radiotherapy. It has been used before each in an attempt to preserve the bladder and decrease recurrence rates. Alternatively, it has been employed postoperatively in patients who have undergone cystectomy and have been found to be at high risk of recurrence. In current practice, adjuvant chemotherapy when indicated—ie, when the primary tumor invades perivesical fat or adjacent organs or when lymph nodes are found to have metastatic disease—is being offered mainly to patients being treated with radical cystectomy. It is used less often for patients with unresectable disease (extension to pelvic side wall).

Bladder Cancer. Pathology & Selection of Treatment.

Pathology & Selection of Treatment

Ninety-eight percent of primary bladder cancers are epithelial malignancies, with the majority being transitional cell carcinomas (90%). These latter cancers most often appear as papillary growths, but higher-grade lesions are often sessile and ulcerated. Grading is based on histologic architecture: size, pleomorphism, mitotic rate, and hyperchromatism. The frequency of recurrence and progression is strongly correlated with grade. Whereas progression may be noted in few grade I cancers (19–37%), it is common with poorly differentiated lesions (33–67%). Carcinoma in situ is recognizable as a flat, nonpapillary, anaplastic epithelium and may occur focally or diffusely, but it is most often found in association with papillary bladder cancers. Its presence identifies a patient at increased risk of recurrence and progression.
Adenocarcinomas and squamous cell cancers account for approximately 2% and 7% (respectively) of all bladder cancers detected in the USA. The latter is often associated with schistosomiasis, vesical calculi, or chronic catheter use.
Bladder cancer staging is based on the extent of bladder wall penetration and the presence of either regional or distant metastases. The TNM classification of the American Joint Cancer Committee for bladder cancer is shown in Table 23–11.

Table 23–11. TNM staging system for bladder cancer.
T: Primary tumor
Tx Cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ (CIS)
Ta Noninvasive papillary carcinoma
T1 Invasion into lamina propria
T2 Invasion into superficial layer of muscularis propria
T3a Invasion into deep layer of muscularis propria
T3b Invasion through serosa into perivesical fat
T4a Invasion into adjacent organs
T4b Invasion into pelvic sidewall
N: Regional lymph nodes
Nx Cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in a single lymph node £ 2 cm
N2 Metastasis in a single lymph node > 2 cm and < 5 cm or multiple
nodes none > 5 cm
N3 Metastasis in lymph node > 5 cm
M: Distant metastasis
Mx Cannot be assessed
M0 No distant metastasis
M1 Distant metastasis present

The natural history of bladder cancer is based on two separate but related processes: tumor recurrence and progression to higher stage disease. Both are related to tumor grade and stage. At initial presentation, approximately 50–80% of bladder cancers will be superficial: Ta, Tis, T1. Lymph node metastases and progression are uncommon in such patients when they are properly treated, and survival is excellent at 81%. Patients with superficial cancers (Ta, T1) are treated with complete transurethral resection and the selective use of intravesical chemotherapy. The latter is used to prevent or delay recurrence. Patients who present with large, high-grade, recurrent Ta lesions, T1 cancers, and those with carcinoma in situ are good candidates for intravesical chemotherapy. Patients with more invasive (T2, T3) but still localized cancers are at risk of both nodal metastases and progression, and they require more aggressive surgery, irradiation, or the combination of chemotherapy and selective surgery or irradiation due to the much higher risk of progression compared to patients with lower-stage lesions. Patients with evidence of lymph node or distant metastases should undergo systemic chemotherapy initially.

Bladder Cancer

Bladder cancer is the second most common urologic cancer. Bladder cancer occurs more commonly in men than women (2.7:1), and the mean age at diagnosis is 65 years. Cigarette smoking and exposure to industrial dyes or solvents are risk factors for the disease and account for approximately 60% and 15% of new cases, respectively.

Clinical Findings

A. Symptoms and Signs: Hematuria—gross or microscopic, chronic or intermittent—is the presenting symptom in 85–90% of patients with bladder cancer. Irritative voiding symptoms (urinary frequency and urgency) will occur in a small percentage of patients as a result of the location or size of the cancer. Most patients with bladder cancer will fail to have signs of the disease because of its superficial nature. Masses detected on bimanual examination may be present in patients with large-volume or deeply infiltrating cancers. Hepatomegaly or supraclavicular lymphadenopathy may be present in patients with metastatic disease, and lymphedema of the lower extremities may be present as a result of locally advanced cancers or metastases to pelvic lymph nodes.

B. Laboratory Findings: Urinalysis will reveal hematuria in the majority of cases. On occasion, it may be accompanied by pyuria. Azotemia may be present in a small number of cases associated with ureteral obstruction. Anemia may occasionally be due to chronic blood loss or to bone marrow metastases. Exfoliated cells from normal and abnormal urothelium can be readily detected in voided urine specimens. Cytology may be useful in detecting the disease at the time of initial presentation or to detect recurrence. Cytology is very sensitive in detecting cancers of higher grade and stage (80–90%) but less so in detecting superficial or well-differentiated lesions (50%). Sensitivity of detection using exfoliated cells may be enhanced by flow cytometry.

C. Imaging: Bladder cancers may be detected using intravenous urography, ultrasound, CT, or MRI where filling defects within the bladder are noted. However, the presence of cancer is confirmed by cystoscopy and biopsy, so imaging is useful primarily for evaluating the upper urinary tract and in staging the more advanced lesions.

D. Cystourethroscopy and Biopsy: The diagnosis and staging of bladder cancers is made by cystoscopy and transurethral resection. If cystoscopy—performed usually under local anesthesia—confirms the presence of bladder cancer, the patient is scheduled for transurethral resection under general or regional anesthesia. A careful bimanual examination is performed initially and at the end of the procedure, noting the size, position, and degree of fixation of a mass, if present. Any suspicious lesions are resected using electrocautery. Resection is carried down to the muscular elements of the bladder wall so as to allow complete staging. Random bladder and, on occasion, prostatic urethral biopsies are performed to detect occult disease elsewhere in the bladder and, therefore, identify patients at high risk of recurrence and progression.

Basal Cell Cancer. Treatment.

Treatment
Electrodesiccation and curettage.

This treatment is most beneficial for nodular BCCs less than 6 mm in diameter, regardless of anatomic site; selected larger BCCs, depending on their anatomic site; and superficial BCCs. It is not appropriate for morpheaform BCCs because margins cannot be clinically defined. Lesions on the nose and nasolabial folds may be treated if they are well defined and very small; otherwise these high-risk areas should be treated by Mohs’ micrographic surgery. However, the treatment is particularly useful for ear lesions, where mobilization of skin for closure after excision is difficult.
Curettage requires firm dermis on all sides and below the tumor to enable the curette to distinguish between dermis and soft tumor. If the tumor encroaches on the fat, the curette cannot distinguish between fat and soft tumor, and an alternate procedure must be used. Curettage should be avoided for lesions on the back and shoulders, where the dermis is thick, unless the BCCs are superficial and small. Proper technique requires vigorous curettage, usually two to three times; therefore, lesions on the eyelid or lip area are treated by other methods. It is especially useful for lower extremity tumors, where tissue mobilization for excision may be difficult. Wounds created by electrosurgery ooze serum and accumulate crust during a 2- to 6-week healing period.
Excision surgery.
Excision surgery is preferred for large tumors with well-defined borders on the cheeks, forehead, trunk, and legs. The cosmetic result is good and healing time is less than that required for electrosurgery. Excision with primary closure is technically difficult on the ears and nose. The advantage of feeling the tumor with a curette is lost and adequate margins must be taken. A 98% cure rate was achieved in one study when BCCs less than 2 cm were excised with excisional margins of 4 mm around the tumor. One large series revealed 5-year recurrence rates of BCCs excised from various anatomic sites: 0.7% on the neck, trunk, and extremities; 3.2% on the head if lesions were less than 6 mm in diameter; 5.2% on the head if lesions were 6 to 9 mm in diameter; and 9.0% on the head if lesions were 10 mm or more in diameter.
INCOMPLETELY RESECTED BCC.
Adequate excision, peripherally and in depth, is the key to surgical control, and the demonstration of tumor cells at the margins of excision is associated with recurrence rates of more than 30%. Data support the policy of immediate re-excision for all patients with incompletely excised basal cell carcinomas rather than a “wait-and-see” policy after incomplete excision. Re-excision may not be necessary if the patient’s life span is limited or if treatment of a possible recurrence would not be difficult.
Cryosurgery.
Cryosurgery with liquid nitrogen delivered with a spray apparatus or a cryoprobe is appropriate for small-to-large BCCs of the nodular and superficial types with clearly definable margins (laterally and in depth). It is not indicated for tumors deeper than 3 mm unless thermocouples are used to measure depth of freeze. A biopsy is performed as a separate operation before the cryosurgical procedure to determine cell type and extent of the tumor or just before the cryosurgery if there is no doubt about the diagnosis. Postoperative pain is moderate to severe. The appearance of a wound a few days after treatment is sometimes alarming to patients.
Mohs’ micrographic surgery.
Mohs’ surgery is a microscopically controlled technique that may be used for all types and sizes of BCCs. The procedure is unnecessarily destructive for smaller lesions or for lesions with well-defined clinical margins, such as nodular or superficial multicentric BCCs.
Mohs’ surgery is the treatment of choice for most sclerosing BCCs and other BCCs with poorly defined clinical margins; for tumors in areas of potentially high recurrence, such as the nose or eyelid; for very large primary tumors; and for large recurrent BCCs

Basal Cell Cancer

Basal cell carcinoma (BCC) is the most common malignant cutaneous neoplasm in humans. The most common presenting complaint is a bleeding or scabbing sore that heals and recurs. The tumor rarely metastasizes. BCC advances by direct extension and destroys normal tissue. Untreated, the cancer can destroy the whole side of the face or penetrate subcutaneous tissue into the bone and brain.

Risk factors.
Fair skin and the degree of sun exposure are important risk factors. Outdoor workers and people who live in southern latitudes with higher levels of ambient ultraviolet B radiation are at greater risk. Men have a significantly higher incidence than women. Tanning salons with equipment that emits ultraviolet A or B radiation are also damaging and increase the risk of BCC.

Location.
Eighty-five percent of all BCCs appear on the head and neck region; 25% to 30% occur on the nose alone, the most common site. BCC is rarely found on the backs of the hands, although this site receives a significant amount of solar radiation. Tumors also occur in sites protected from the sun, such as the genitals and breasts. BCC in blacks is rare.

PATHOPHYSIOLOGY
BCCs arise from basal keratinocytes of the epidermis and adnexal structures (hair follicles, eccrine sweat ducts). Ultraviolet B (UVB) radiation (sunburn spectrum, 290 to 320 nm) is important for the induction of BCC. UVB radiation damages DNA and its repair system and alters the immune system. Depletion of ozone in the earth’s atmosphere results in higher levels of UVB radiation at the earth’s surface. Longer wavelength UVA radiation damages DNA and is also carcinogenic.
BCC grows by direct extension and appears to require the surrounding stroma to support its growth. This may explain why the cells are not capable of metastasizing through blood vessels or lymphatics. The course of BCC is unpredictable. BCC can remain small for years with little tendency to grow, particularly in the elderly, or it may grow rapidly or proceed by successive spurts of extension of tumor and partial regression.
BCC occurs at the site of previous trauma, such as scars, thermal burns, and injury. BCC occurs years later at sites treated with ionizing radiation. The tumor appears 3 months to 7 or more years later at the site of a well-remembered injury.

CLINICAL TYPES
BCC occurs in many different clinical forms, which vary in appearance and malignant potential.

Nodular BCC.
Nodular BCC is the most common form. The lesion begins as a pearly white or pink, dome-shaped papule resembling a molluscum contagiosum or dermal nevus. The mass extends peripherally. The lesion may remain flat. Traction on the surrounding skin accentuates the pearly border. Telangiectatic vessels become prominent and easily recognizable through the thin epidermis as the lesion enlarges. The growth pattern is irregular, forming an oval mass whereby the surface may become multilobular. The center frequently ulcerates and bleeds and subsequently accumulates crust and scale. Ulcerated BCCs were formerly designated rodent ulcers.
Ulcerated areas heal with scarring, and patients often assume their conditions are improving. This cycle of growth, ulceration, and healing continues as the mass extends peripherally and deeper; masses of enormous size may be attained. BCCs may present as nonhealing leg ulcers. Biopsy specimens should be taken of leg ulcers that do not respond to treatment. The tissue mass of a nodular BCC has a distinctive consistency that can be appreciated during curettage or biopsy. It has poor cohesive forces and collapses or breaks down when manipulated with a curette. This is an important diagnostic feature that supports the clinical impression during the biopsy procedure.
Pigmented BCC.
BCCs may contain melanin that imparts a brown, black, or blue color through all or part of the lesion. Clinically, the lesion resembles a melanoma or pigmented seborrheic keratosis, but close inspection reveals the characteristically elevated, pearly white, translucent border, and the biopsy confirms the diagnosis. The histologic pattern most frequently associated with pigment is the nodular pattern.
Management and risk of recurrence

There are several factors to consider before choosing the best treatment modality. The most important are clinical presentation, cell type, tumor size, and location.
Clinical type.

Nodular and superficial BCCs are the least aggressive and can be completely removed by electrodesiccation and curettage or by simple surgical excision.
Histologic type.

The micronodular, infiltrative, and morpheaform BCCs have a higher incidence of positive tumor margins (18.6%, 26.5%, and 33.3%, respectively) after excision and have the greatest recurrence rate. Clinically, BCCs with these patterns have poorly defined borders and are not apparent during physical examination. They subtly extend into surrounding tissue and are easily missed by blind treatment techniques such as surgical excision. An average of 7.2 mm of subclinical tumor extension was found in mopheaform BCCs in one study, compared with 2.1 mm of extension in well-circumscribed nodular lesions. Routine pathologic examination of surgically excised BCCs may not detect a small nodule or strand of BCC on the other side of the excision margin. These tumors need more aggressive treatment with wide excision or microscopically controlled surgery.
Tumor size.
In general, electrodesiccation and curettage afford excellent results for small (less than 2 cm) nodular BCCs located on the forehead and cheeks. Nodular BCCs on the forehead and cheek that are larger and have well-defined margins should be excised and closed; electrosurgery for large tumors may result in large, unsightly scars. The margins of sclerosing BCCs cannot be determined by inspection, and either excision or, preferably, Mohs’ micrographic surgery should be performed. Superficial BCCs of any size can be adequately removed by electrosurgery.
Location.
Tumors about the nose, eye, and ear require special consideration. BCCs of the medial canthus are particularly dangerous. The skin rests close to bone and cartilage, and tumor cells initially invade and proceed to migrate undetected along periosteum or perichondrium. Healing occurs over inadequately treated tumors, and deep invasion and lateral extension can remain undetected, resulting in a tumor of massive proportions. Extension to the eye and brain is possible.