Oncology

A family history of colorectal cancer or adenomatous polyps significantly increases a person's risk for colorectal cancer. The presence of colorectal cancer in a first-degree relative carries a twofold to threefold increased lifetime risk over the general population; that risk is doubled again if the affected relative was diagnosed before age 45 years. If two first-degree relatives have colorectal cancer, the colorectal cancer risk approaches 20%. For persons with a family history of colorectal cancer in a first-degree relative, screening is initiated either at age 40 years or beginning 10 years earlier than the diagnosis of the youngest affected family member. If normal, colonoscopy is repeated every 3 to 5 years. Because this patient had colonoscopy screening at the age of 50 years, colonoscopy should be offered at some time between ages 53 and 55 years.Familial adenomatous polyposis and attenuated familial adenomatous polyposis are most commonly diagnosed after polyposis is detected on endoscopy. In these patients, testing for mutations in the APC gene is reasonable. However, this patient does not have a personal history of polyposis.Performing colonoscopy at age 50 years and then every 10 years is the recommendation for patients at average risk for colorectal cancer. Persons at average risk for colorectal cancer include those with no personal or family history of colon adenoma or cancer and who do not have a condition that predisposes them to cancer.Patients with inflammatory bowel disease have an increased risk for colorectal cancer. The most reliable estimates suggest an annual colorectal cancer rate in extensive colitis of at least 0.5% per year after the first decade of colitis. Screening recommendations include colonoscopy every 1 to 2 years beginning 8 years after diagnosis. This screening interval is not appropriate for this patient who does not have inflammatory bowel disease.

Paget disease of the breast, defined as a persistent, scaling, eczematous, or ulcerated lesion involving the nipple/areolar complex. Histologically, the hallmark of Paget disease of the breast is the presence of malignant, intraepithelial adenocarcinoma cells (Paget cells) within the epidermis of the nipple associated with an underlying invasive or intraductal cancer. It is often misdiagnosed on the first presentation as either eczema or psoriasis, but when there is a lack of response to appropriate therapy, a biopsy should be performed.

The Breast Imaging Reporting and Data System (BI-RADS) is a standardized reporting system for mammography findings and a source of recommendations for further management. Category assignments are either incomplete (category 0) or final assessment (categories 1 through 6). Category 2 findings correspond to findings compatible with benign nodules or cysts or benign calcifications. But because this patient's mass has persisted through several menstrual cycles, she needs further evaluation despite the normal mammogram. Because she is older than 30 years and the mammogram is classified as BI-RADS 2, the ultrasound is the next appropriate test. This is true for mammograms rated BI-RADS 1-3. Ultrasound serves to distinguish cystic from solid masses. A cystic mass should be aspirated and the fluid sent for cytologic evaluation if bloody or recurrent. A solid mass requires biopsy by fine-needle aspiration, core needle, or excision. If the mammogram is classified as BI-RADS 4 or 5, malignancy is much more likely and a tissue diagnosis with fine needle aspirate or biopsy is the most appropriate management.

Inherited germline abnormalities in BRCA-1 and BRCA-2 genes confer very high risk for breast and ovarian cancer (absolute risk of breast cancer greater than 60% by age 50 years). Fewer than 5% of all cases of breast cancer are attributed to germline abnormalities in these genes, however, and the prevalence of these abnormalities in the general population is approximately 1/800. Testing for BRCA-1 and BRCA-2 genes should be performed only in women who appear to have a genetic risk (multiple relatives with breast or ovarian cancer, especially with early-onset of disease). These women and their families should be referred to a genetic counselor for discussion and consideration of these complex issues. This patient does not have an increased genetic risk for breast cancer and testing for BRCA-1and BRCA-2 genes is not indicated.

• A patient with a breast mass requires triple assessment: palpation, mammography with or without ultrasonography, and surgical evaluation for biopsy. Mammograms may be normal in 10% to 15% of patients with breast lumps, some of which may be cancerous. After performance of bilateral diagnostic mammography, the initial focus of the workup of a dominant breast mass is to distinguish a simple cyst from a solid mass by fine-needle aspiration (FNA) or ultrasonography. If the fluid from FNA is bloody, the fluid should undergo cytologic evaluation. Women with simple cysts should undergo a breast examination 4 to 6 weeks after cyst aspiration to evaluate for cyst recurrence or a residual lump. A solid mass requires a tissue diagnosis by fine-needle aspiration biopsy (FNAB), core-needle biopsy, or excisional biopsy. Patients with benign FNAB or core-needle biopsy results and negative mammogram require close clinical follow-up of the breast abnormality.
• The next step is a tumor estrogen-receptor (ER) and progesterone-receptor (PR) assay. This patient has early-stage breast cancer (stage I) based on the tumor size (<2 cm); absent lymph node involvement; and no apparent metastases based on her symptoms, physical examination findings, and routine blood tests. The step that would be most helpful in directing the approach to management of this patient is to perform an assay for expression of ER and PR to determine the optimal systemic treatment, and this evaluative step should be performed in all cases of primary breast cancer. Endocrine therapy (for example, tamoxifen, aromatase inhibitors, fulvestrant, and megestrol acetate) is beneficial only in patients with ER–positive or PR–positive tumors. Patients whose tumors are hormone receptor–negative are refractory to endocrine treatment and should receive chemotherapy instead.In patients with early-stage breast cancer, the routine evaluation is limited to a thorough history and physical examination, diagnostic mammography, chest radiography, and routine blood tests (including liver chemistry tests). The use of additional imaging studies or blood tests is not warranted in the absence of specific symptoms because they may lead to the detection of abnormalities of no significance (a false-positive test result).

Common signs and symptoms of colorectal cancer are influenced by the site of the primary tumor and may include a change in bowel habits, diarrhea, constipation, a feeling that the bowel does not empty completely, bright red blood in the stool or melanotic stools, and stools that are narrower in caliber than usual. Other signs include general abdominal discomfort (frequent gas pains, bloating, fullness, or cramps), weight loss for no known reason, fatigue, and vomiting. Findings that should prompt investigation for colon cancer include a rectal or abdominal mass, hepatomegaly, abdominal tenderness, or iron deficiency anemia. If one or more such findings are present, a full colorectal examination with colonoscopy should be done. However, the examination may be limited to sigmoidoscopy for rectal bleeding in most persons younger than 40 years of age because colorectal cancer is uncommon in such patients (except those with hereditary colorectal cancer syndromes), and in most young patients with hematochezia, a rectosigmoid lesion, usually hemorrhoids, is the cause of rectal bleeding. This patient is older than 40 years, has concerning symptoms, and therefore requires an immediate colonoscopy.

This patient has a positive result on a screening test for colorectal neoplasia and should be evaluated next with colonoscopy. Fecal occult blood testing (FOBT) is associated with a 15% to 33% reduction in mortality rates from colorectal cancer when annual or biennial testing is done. Six-window FOBT is performed by taking two separate samples from each of three spontaneously passed stools (six samples). Even though only one of three of this patient's samples submitted for fecal occult blood testing was positive, she requires appropriate follow-up with a diagnostic test such as colonoscopy.

This patient has pancolitis of 8 years' duration. The inflammation involves the ileum and proximal colon. The colon cancer risk in patients with ulcerative colitis or Crohn disease reaches a significant level (estimate annual cancer risk of 1% to 2% per year) after 8 years of inflammation. The cancer risk is slightly delayed for patients with inflammation limited to the distal colon. The recommendation is to initiate a surveillance program with colonoscopy 8 years after onset of disease, with follow-up colonoscopy every 1 to 2 years thereafter. Random biopsies are performed in four-quadrant fashion throughout the entire colon. Colectomy is recommended for patients with dysplastic findings on biopsy.

This patient requires no further follow up. Studies of chest CT screening have shown that 25% to 50% of patients have one or more pulmonary nodules detected on the initial CT scan. Even in patients at relatively high risk for lung cancer, the likelihood that a small nodule is malignant is low. For example, the risk of malignancy is about 0.2% for nodules smaller than 3 mm in diameter and 0.9% for nodules measuring 4 to 7 mm in diameter. The Fleischner Society recommendations include no follow-up for low-risk patients with nodules 4 mm or smaller and follow-up CT at 12 months for patients with such nodules who are at risk for lung cancer. This small nodule is not likely to be visible on chest radiograph, and, therefore, such imaging would not be helpful.

• The most appropriate management for this patient is supraclavicular lymph node biopsy. In the evaluation of a patient with suspected lung cancer, obtaining a tissue diagnosis is critical for treatment planning and determining prognosis. Staging the cancer and determining whether the patient is a candidate for resection are also important parts of the evaluation. In this patient, determining whether the supraclavicular lymph node contains non–small cell cancer should be done, and the next step in the evaluation would be to sample the lymph node; this would likely establish both a diagnosis and that the patient has advanced unresectable disease.
• Biopsy of the mass or hilar lymph nodes by CT guidance or bronchoscopy would establish the diagnosis but not the stage and would not determine resectability

SCLC is considered a systemic disease; patients who present with seemingly localized disease almost always have concurrent micrometastases and consequently the more complicated staging system of non–small cell lung cancer does not apply. Patients with visibly localized disease that can be encompassed within a radiation therapy port are designated as having limited-stage disease. Patients with tumor beyond the confines of a radiation port are considered to have extensive-stage disease. Chemotherapy plus radiation therapy is considered first-line treatment for patients with limited-stage SCLC. Typical regimens consist of a combination of a platinum agent (carboplatin or cisplatin) and etoposide or irinotecan. Combination chemotherapy and radiation therapy is associated with a substantially improved median survival compared with chemotherapy, surgery, or radiotherapy alone, although cure remains rare.

• Patients with an elevated or rising serum PSA level noted during routine screening should also undergo prostate biopsy, even if they are asymptomatic. Specifically, these patients need ultrasound-guided biopsies of their prostate (typically in 6 random areas) to assess for the presence of prostate cancer. After prostate cancer is diagnosed, additional studies such as a bone scan or CT scan of the abdomen and pelvis should be considered in patients with signs or symptoms suggestive of distant spread of the malignancy.
• Pathologic proof of prostate cancer is needed before embarking on definitive therapy such as radical prostatectomy. A PSA greater than 4.0 ng/mL (4.0 µg/L) is only 25% sensitive for prostate cancer. In the absence of a histologic diagnosis for prostate cancer, surgical intervention is not appropriate.Patients with “borderline” PSA measurements might be appropriately managed by repeating the measurement in 6 months; however, this patient has had a rapid rise in the PSA level. Any rise greater than 0.75 ng/mL/year (0.75 µg/L/year) is considered abnormal and should be evaluated.

• (USPSTF) concluded that the evidence was insufficient to recommend for or against prostate cancer screening using prostate-specific antigen (PSA) testing or digital rectal examination (DRE) and recommended that physicians discuss potential, but uncertain, benefits and possible harms (complications of future diagnostic testing and therapies, including incontinence; erectile dysfunction; and bowel dysfunction) before ordering PSA testing. The USPSTF also recommended against prostate cancer screening in men aged 75 years or older. They noted that if screening were to be performed, men ages 50 to 70 years would benefit most. The USPSTF stated that men should be informed of the gaps and conflicting results in the evidence and should be assisted in considering their personal preferences before deciding whether to be tested. The American Cancer Society recommends that PSA testing be offered to men at age 50 years (age 45 years for men at high risk owing to a positive family history of prostate cancer or who are black) and that information about limitations and benefits be provided.
• Two large randomized screening trials studied the effect of screening on rate of death from prostate cancer. There was no difference in the rate of death from prostate cancer between screened and control groups in one study. In the second study, the prostate cancer death rate per 1000 person-years was 0.35 in the screened group versus 0.41 in the control group (P = 0.04). The number needed to screen was 1410 and the number needed to treat to prevent one prostate cancer-related death over a 10-year period was 48. About 50% to 75% of those 48 men would be expected to have some complication of treatment. In evaluating the limited benefit demonstrated in this trial, one must consider the increased number of false diagnoses (false-positive rate of 75.9% of those undergoing biopsy) and unnecessary treatments.

According to the U.S. Preventive Services Task Force (USPSTF), there is inadequate evidence to suggest that treatment of patients younger than 75 years with screening-detected prostate cancer results in improved outcomes compared with treatment of patients with clinically detected (symptomatic) prostate cancer. Adequate evidence indicates that the incremental benefits of treatment of patients 75 years of age or older with screening-detected prostate cancer are small to none. Moderate to substantial harms, including erectile dysfunction, urinary incontinence, bowel dysfunction, and death, in addition to small harms, including prostate biopsy-induced pain and discomfort and psychological effects of false-positive test results, are associated with prostate cancer screening. Because prostate cancer symptoms may not develop in many older patients who receive treatment for screening-detected prostate cancer during their lifetime, consideration of these harms is important.In view of the recommendations from the USPSTF and the evidence supporting those recommendations, repeating the PSA, bone scan, and transrectal prostate biopsy are all inappropriate choices for this 80-year-old man with significant comorbidities.

• This patient has metastatic prostate cancer involving the bones. Prostate cancer is a hormone-responsive tumor, and his disease will most likely respond to hormone deprivation therapy with surgical castration or gonadotropin hormone–releasing hormone (GnRH) agonists such as leuprolide. GnRH therapy causes impotence, hot flushes, gynecomastia, and loss of libido, as does orchiectomy. Patients may experience tumor-flare reactions with the use of GnRH agonists, which initially cause an increase in luteinizing and follicle-stimulating hormones. These hormones lead to a transient increase in testosterone, which can exacerbate prostate cancer symptoms. This reaction can be prevented by a brief course of concomitant antiandrogen therapy with agents such as bicalutamide, nilutamide, or flutamide.
• Although docetaxel-based chemotherapy has been shown to improve survival, this agent is generally indicated only for patients with hormone-refractory cancer. Several studies have demonstrated an improvement in overall survival with docetaxel-based chemotherapy in this setting.

The most appropriate next management step is colposcopy. The most common abnormal finding following cervical cancer screening is atypical squamous cells (ASC), which is reported in approximately 5% of test results. Most ASC abnormalities resolve spontaneously, but approximately 15% of patients harbor a precancerous lesion discovered on biopsy. Adult women with ASC should be tested for human papillomavirus infection. If the patient with ASC tests positive for high-risk human papillomavirus subtypes (for example, 16 or 18), colposcopy with biopsy is performed. Colposcopy provides an illuminated, magnified view of the cervix, vagina, and vulva and enhances the ability of the operator to detect premalignant and malignant lesions that can biopsied.In a patient with ASC and high-risk human papillomavirus infection, delaying investigation for the presence of possible premalignant or malignant lesions for 1 year is excessively long and inappropriate. There is no effective treatment for cervical human papillomavirus infection, including interferon.

• The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends the quadrivalent human papillomavirus (HPV) vaccine for cervical cancer prevention for all girls and women between the ages of 9 and 26 years regardless of sexual activity. The Gardasil vaccine has a high success rate in preventing infections with HPV strains 6, 11, 16, and 18, which cause most cases of genital warts and cervical cancer.
• HPV infection is predominantly spread by sexual contact. This patient states she is not sexually active; however, the vaccine should be recommended now because it is of low risk, and vaccine efficacy lasts for at least several years. The vaccine does not protect against all types of HPV, and roughly 30% of cervical cancers will not be prevented by the vaccine; therefore, women should continue to receive regular Pap smears even after completing the vaccination series.

• She is in a long-term, monogamous relationship and has had many normal Pap smears, so it is appropriate to lengthen the screening interval for Pap tests to every 3 years. The United States Preventive Services Task Force recommends cervical cancer screening for women who are sexually active and have a cervix. Screening should begin within 3 years of onset of sexual activity but no later than age 21 years. After age 65 years, the effectiveness of screening is low in women who have had recent negative Pap smears. Women at normal risk can be screened every 3 years, although the American Cancer Society recommends waiting until age 30 years before lengthening the screening interval from an annual basis. Annual Pap tests do not identify more invasive cancer than tests performed every 2 or 3 years in low-risk women who have had several normal tests.
• Women who have human immunodeficiency virus infection should be screened for cervical cancer more frequently, because human papillomavirus can grow faster and lesions can progress more quickly in significantly immunosuppressed patients. Women who have multiple sex partners, have a history of abnormal Pap smears, or have recently been diagnosed with a sexually transmitted disease are at higher risk for cervical cancer, and current guidelines suggest screening such women annually.

This lesion is most consistent with squamous cell carcinoma in situ (Bowen disease). It is a form of intraepidermal carcinoma, a malignant tumor of keratinocytes. It presents as a single lesion in two thirds of cases. The head, neck, and extremities are the most commonly affected sites in men. The cheeks and lower extremities are the most commonly affected sites in women. Lesions vary from a few millimeters to several centimeters in diameter. Lesions can arise de novo or from a preexisting actinic keratosis. Etiology is most likely multifactorial and includes chronic ultraviolet radiation, arsenic exposure, human papillomavirus, immunosuppression, genetic factors, trauma, x-ray radiation, and chemical carcinogens.

Superficial spreading melanoma presents as a variably pigmented plaque with an irregular border, ranging from a few to several centimeters. It is not scaly. It can occur anywhere, but is commonly seen on the back in men and the legs in women.

Nodular melanoma often presents as uniformly dark blue or black “berry-like” lesions that most commonly originate from normal skin. It is most often found in people aged 60 years or older. Nodular melanomas often do not fulfill the ABCDE (asymmetry, irregular borders,color variegation, expanding diameter,evolution over time) criteria for melanoma and tend to expand vertically rather than horizontally. Nodular melanomas are mostly symmetric, elevated, and one color.

This patient has actinic keratoses, common lesions that occur on sun-exposed skin of older white-skinned persons. Actinic keratoses are believed to be the earliest clinically recognized step in a biologic continuum that may result in invasive squamous cell carcinoma. Actinic keratoses are 1- to 3-mm, elevated, flesh-colored or red papules, surrounded by a whitish scale. They are often easier to feel as “rough spots” on the skin than they are to see. Most patients will have, on average, 6 to 8 lesions. Most remain stable and some regress, but others enlarge to become invasive squamous cell carcinomas. The appearance of the patient's lesion is not consistent with basal cell carcinoma, melanoma, or seborrheic keratosis.

Keratoacanthoma is an epithelial neoplasm that is characterized by rapid growth over 2 to 6 weeks and by a crater-like configuration. Early lesions are frequently misdiagnosed as skin infections. The typical early lesion is a hard, erythematous nodule with a keratotic (horny) center. Keratoacanthomas typically occur on heavily sun-damaged skin, usually in older persons, with a peak age of 60 years. As the lesion enlarges, the center of the crater becomes more prominent. Unlike typical squamous cell carcinomas, keratoacanthomas are capable of spontaneous resolution by terminal differentiation, in which the tumor “keratinizes itself to death.” The clinical presentation and characteristic histologic features establish the diagnosis.Because keratoacanthomas may cause significant local tissue destruction, simple observation is generally not recommended despite the tendency for spontaneous involution. Prompt surgical excision is recommended for solitary lesions on the trunk or extremities. Intralesional 5-fluorouracil or methotrexate, topical imiquimod, and radiation therapy have also been used to treat large lesions or those in areas where surgical excision would be anatomically difficult.

An appropriate solution would be to give him sustained-release morphine twice daily. A breakthrough pain strategy should be continued so the patient has options if the longer-acting pain medication does not provide complete relief. When adding a long-acting opioid, a strategy to avoid overmedication is to give a starting dose of 30% to 50% of the patient's average 24-hour dosage of narcotic. The dose of the opioid for breakthrough pain is calculated as 10% of the total daily opioid dose given as an immediate-release opioid.