Accounting for 13% of all new cancers and 29% of all cancer deaths, lung cancer is the predominant cause of cancer deaths across all race, gender, and ethnic groups in the United States. In 2006, an estimated 162,460 Americans will die from lung cancer (ACS, 2006). Squamous cell lung cancers tend to remain more localized than the other cell types and thus have the best chance for surgical cure. The other major cell types—adenocarcinoma and large-cell and small-cell lung cancers—tend to metastasize early and frequently (Murren, Turrisi, & Pass, 2005; Schrump, Altorki, Henschke et al., 2005).

In addition to the common sites of metastasis as outlined in Table 15-1, all cell types of lung cancer are highly likely to metastasize to mediastinal lymph nodes. Other potential sites of metastasis include the pericardium and the pancreas. Lung cancers may also lead to the following paraneoplastic syndromes (Murren et al., 2005; Schrump et al., 2005):

The pattern of early and frequent metastasis in lung cancer often translates into patients being diagnosed when the disease has reached an advanced stage. Indeed, 60% of small-cell lung cancers and 40% of non–small-cell lung cancers present in stage IV (Smith & Khuri, 2004). The 5-year survival rate for individuals diagnosed with distant metastasis is only 2.1% (ACS, 2006). Most patients should be referred for palliative care from the time of diagnosis.

Essentially all chemotherapy for advanced lung cancer is palliative in that cure is not the aim. Survival may be prolonged with chemotherapy, but the potential for increased length of life must be balanced against the effect on quality of life, toxicity of the chemotherapy, and costs of treatment. It is important to note that patients who respond best to chemotherapy are those who have not been previously treated with chemotherapy and who have a good performance status. Patients who have disease progression while receiving chemotherapy, relapse soon after completion of chemotherapy, or have a compromised performance status have a much lower potential for favorable outcomes from chemotherapy.

Colorectal cancer is the third leading cause of cancer deaths for men and for women and is the overall second leading cause of cancer deaths (men and women combined) in the United States. An estimated 55,170 will die of colorectal cancer in 2006, accounting for 10% of all cancer deaths (ACS, 2006). As with all cancers, the stage at diagnosis is the primary determinant of prognosis. The 5-year survival rate for colorectal cancers with distant metastasis is 9.7% (ACS, 2006).

Sites of metastasis include the lymph nodes, liver, lung, brain, bone, and adrenal glands (Libuiti, Saltz, Rustgi et al., 2005). These tumors are also likely to cause obstruction of the bowel, leading to nausea and vomiting and abdominal distention; obstruction of the ureter, causing flank pain, hydronephrosis, and renal failure; and obstruction of the urethra, leading to urinary retention and risk of bladder infection.

Until the past few years, colorectal tumors were considered resistant to most antineoplastic agents. Newer chemotherapy drugs and molecularly targeted therapies are improving survival in colorectal cancer (Wilkes, 2005). There is some controversy regarding the optimal duration of chemotherapy for metastatic disease. It appears that continuation of chemotherapy until clinical deterioration or disease progression has no advantage over a planned discontinuation of therapy after a fixed time (e.g., 3 months or 6 months). Patients with good performance status, good bone marrow reserve, and good organ function appear to benefit more from chemotherapy than do those who do not meet these criteria (Libuiti et al., 2005).

In the United States, breast cancer is the most frequent new cancer diagnosis in women and the second leading cause of cancer deaths in women. An estimated 41,430 patients will die from breast cancer in 2006 (ACS, 2006). The mortality rate has declined over the past decade largely due to early detection and the use of aggressive multimodality treatments (Wood, Muss, Solin et al., 2005). The 5-year survival rate for patients with distant metastasis is 26.1% (ACS, 2006). Poor prognostic indicators include stage IV disease, young age, estrogen receptor (ER)–and progesterone receptor (PR)–negative tumors, and tumors with HER2 overexpression. Stage IV breast cancer is not considered curable. The median survival for patients with metastatic disease is 18 to 24 months. However, many treatments are available to control metastasis and prolong life considerably, and with newer therapies, it is estimated that approximately 10% of patients with metastasis will survive 10 years or longer (Wood et al., 2005).

Women who receive hormonal therapy and chemotherapy following surgery in early-stage disease demonstrate delayed recurrence and improved overall survival compared with those who do not receive chemotherapy (Wood et al., 2005). Women with ER- and PR-positive tumors tend to respond to hormone therapy. Women with ER- and PR-negative tumors and slowly progressive disease with minimal symptoms should be considered for hormone therapy as well. However, women with ER- and PR-negative tumors with rapidly progressive tumors should be considered for chemotherapy (Wood et al., 2005).

Women with ER-positive tumors with metastatic disease should be treated with hormone therapy before chemotherapy is considered (Wilcken, Hornbuckle, & Ghersi, 2003). Tamoxifen is still considered first-line hormonal therapy for premenopausal women with ER-positive metastatic disease. In postmenopausal women with metastasis, the ideal sequencing of hormonal therapy is not clear; tamoxifen, aromatase inhibitors, and fulvestrant are all considered reasonable choices for first-line therapy at this time (Wood et al., 2005). Improvement in bone pain is the best indication of response to hormone therapy in women with metastasis. Hormone therapy is generally continued as long as symptoms are controlled and side effects are tolerated. If hormone therapy is no longer indicated, the dose of the hormone is weaned slowly to prevent a withdrawal response.

When hormone treatment is no longer effective, chemotherapy is usually considered. Improved survival and symptom control may be possible in stage IV disease with combination chemotherapy, even in women who have previously received chemotherapy (Berruti, Sperone, Bottini et al., 2000; Ghersi, Wilcken, & Simes, 2005; Nagourney, Link, Blitzer et al., 2000; Wood et al., 2005). Taxane-containing regimens have fewer side effects than regimens with platinum-containing chemotherapeutic agents (Carrick, Ghersi, Wilcken et al., 2005; Ghersi et al., 2005). Response rates to initial chemotherapy regimens range from 25% to 60%, with a median time to progression of 6 months. Response rates for second- and third-line treatments diminish by half (Wood et al., 2005). The beneficial effect of chemotherapy, when given for symptom control, should be apparent by the second or third treatment. If the symptom being treated is not improving, carefully evaluate the benefits versus the burdens of continuing treatment should be carefully evaluated.

The lymph nodes are the most frequent site of metastasis. Other sites include the bone, lung, liver, pleura, adrenal glands, kidney, brain, skin, and chest wall. Women with ER- and PR-positive tumors are most likely to develop bone metastasis, and those with ER- and PR-negative tumors tend to have liver and other visceral metastasis (Wood et al., 2005). Due to the proximity of tumors to the skin surface, breast tumors may cause skin lesions that can progress to fungating tumor wounds.

Cancer of the prostate is the most frequent cause of cancer in men, with 234,460 new diagnoses expected in 2006. It is the second leading cause of cancer deaths in men. Approximately 27,350 men will die of prostate cancer in 2006. The 5-year survival rate for patients with distant metastasis is 33.5% (ACS, 2006). Again, distant metastasis is not considered curable, but clearly, with a 5-year survival of 33.5%, men are living for years with metastatic prostate cancer.

Prostate cancers are often androgen dependent. Most tumors will respond to hormonal manipulation, providing symptomatic benefits and a moderate survival benefit (Scher, Leibel, Fuks, et al., 2005). However, the side effects of androgen suppression can reduce the quality of life for some patients (Schmitt, Bennett, Seidenfeld et al., 2000). These tumors are also radiosensitive and may be treated with external beam radiotherapy or implanted radioactive seeds. Systemic irradiation (e.g., strontium 89) may be helpful for managing widely metastatic bone pain, but it is more expensive and no more effective than local field radiotherapy for managing bone pain in a localized area (Finlay, Mason, & Shelley, 2005; Oosterhof, Roberts, de Reijke et al., 2003). Until recently, chemotherapy did not play a role in the management of prostate cancer. Mitoxantrone-based regimens were the first to show palliative benefits in hormone-resistant tumors, but docetaxel-based therapies are also showing promise (Petrylak, Tangen, Hussain et al., 2004; Tannock, de Wit, Berry et al., 2004). Keep in mind that most study subjects showing a good response were less symptomatic and had a good performance status at the initiation of treatment; the benefit and tolerability of chemotherapy regimens in patients with poorer performance status, widely metastatic disease, or some organ system compromise are not known. Clinical trials using vaccines derived from dendritic cells expressing prostatic acid phosphatase are showing promise (Arlen & Gulley, 2005; Vieweg & Dannull, 2005).

Local spread of prostate cancer to the pelvic and abdominal lymph nodes, seminal vesicles, bladder, and peritoneum is common. Frequent sites of metastasis beyond the pelvis are bone (most frequent), lungs, and liver (Scher et al., 2005). Men with prostate cancer are at risk for developing urinary outflow obstruction, leading to urinary frequency, hesitancy, and nocturia; this may progress to urinary retention. They are also at risk for urethral obstruction, causing bladder dilatation, hydronephrosis, and impaired renal function.

Although pancreatic cancer ranks eleventh in incidence of new cancers in the United States, it is the fourth leading cause of cancer deaths. In 2006, an estimated 32,300 patients will die from this malignancy. The prognosis for patients with pancreatic cancer is poor. The 5-year survival rate for all stages is just 4.6%, and for those with distant metastasis, the 5-year survival is only 1.8% (ACS, 2006). The disease generally does not display early symptoms. By the time jaundice is present or pain becomes significant enough for an individual to seek medical evaluation, 80% of pancreatic cancers are metastatic (Yeo et al., 2005).

Treatment options are limited. In the rare instance that disease is localized, surgery offers the only potential for cure, but survival after resection is often still limited. Most often, however, surgery is used for palliation of symptoms by relieving or preventing obstructions of the biliary duct and duodenum. The median survival after palliative surgery is about 6 months (Yeo et al., 2005). Chemotherapy does appear to modestly improve survival and to palliate some symptoms (El-Rayes & Philip, 2003; Yeo et al., 2005). Patients in clinical trials with gemcitabine demonstrated less pain, improved functional ability, and weight gain (Burris, Moore, Anderson et al., 1997). Patients showing the best responses to chemotherapy are treated soon after diagnosis, having not previously received chemotherapy, and have a good performance status. Combination chemotherapy with gemcitabine-based protocols is showing promise but needs further evaluation (Reni, Cordio, Milandri et al., 2005). The role of radiation therapy is limited, but some studies show benefit when chemotherapy is combined with radiation, particularly to shrink tumors preoperatively (Yeo et al., 2005). Palliative uses include relief of intestinal obstruction or unresectable biliary obstruction.