ONCOLOGY Vol 24 No 9

Extramedullary disease in plasma cell disorders can occur as a solitary plasmacytoma or can involve multiple sites with vastly different clinical outcomes. The article by Khaliq et al reports an unusual case of solitary extramedullary plasmacytoma (SEP) of the bladder in which the patient had a favorable outcome with lenalidomide/dexamethasone after failing first-line treatment with radiotherapy. In this context it is interesting to compare clinical outcomes of this entity to two other clinical variants of myeloma: solitary plasmacytoma of bone (SPB), and multiple myeloma with extramedullary plasmacytomas (MM/EP).

Yoga, first described in the Vedic texts of India, has been practiced for millennia. It involves regulated breathing, moving through various postures known as asanas, and meditation, aimed at achieving physical and psychological well-being. Many styles of yoga encompass some or all of these components. Yoga can have a positive impact on quality of life (QOL) in people with and without cancer, by reducing stress and fatigue and improving symptoms of certain inflammatory conditions. In the cancer setting alone, there are at least 10 randomized trials documenting the benefits of yoga on patients’ QOL.

Plasmacytoma is a rare B-lymphocyte neoplastic disorder that usually presents as the generalized disease multiple myeloma. Less than 5% of the cases present as a solitary mass of monoclonal plasma cells in the bone or soft tissue. Although solitary extramedullary plasmacytoma (SEP) may arise in any organ, it rarely involves the urinary bladder. A 67-year-old male without a history of multiple myeloma presented with urinary frequency and nocturia; he was later diagnosed with SEP of the bladder. The patient was initially treated with a course of radiation therapy without symptomatic improvement; therefore a chemotherapy regimen consisting of lenalidomide and dexamethasone was subsequently given for six cycles. SEP usually carries a better prognosis and higher cure rate than solitary plasmacytoma of bone, as SEP is radiation sensitive. The role of adjuvant chemotherapy in the treatment of SEP that is resistant to radiation therapy is not clear, since most of the recommendations have been derived from the experience of head and neck SEP. The literature also lacks recommendations for choice of a chemotherapy regimen and surveillance of isolated bladder plasmacytoma. Here we present the first case of a radiation-resistant solitary plasmacytoma of the bladder that was successfully treated with lenalidomide and dexamethasone with successful clinical remission.

The authors on “Solitary Extramedullary Plasmacytoma of the Bladder” have provided a quick and accurate diagnosis, work-up, and treatment of this solitary extramedullary plasmacytoma. Solitary extramedullary plamacytomas are rare, and account for only 3% of all plasma cell malignancies. Of the 3% of plasma cell malignancies that are diagnosed, the bladder is one of the least common locations. The rarity of the tumor frequently makes the process of making a correct diagnosis difficult.[1] After making the diagnosis with immunohistochemistry, a bone marrow biopsy must be performed to rule out multiple myeloma. Additionally, a body and skeletal survey must show no evidence of additional disease or lytic lesions in order to confirm localized disease. In this case, these procedures were performed accurately and in a timely fashion.

Primary surgery with an abdominoperineal resection (APR) was historically the standard of care for localized anal squamous cell carcinoma. APR achieved 40%-70% survival rates at five years, with local failures from 27%-47%.[1,2] With modern technology and radiation dose escalation, external beam radiation therapy (EBRT) studies have improved complete response rates, decreased morbidity, and improved sphincter preservation rates. Nigro et al added 5-fluorouracil (5FU) and mitomycin C (MMC) to concurrent EBRT [3,4] and impressive complete response rates inspired other groups to investigate the role of chemotherapy as a component of sphincter-preserving therapy. The European Organization for Research and Treatment of Cancer (EORTC) and United Kingdom Coordinating Committee on Cancer Research (UKCCCR) studies reported improved local control and colostomy-free survival when chemotherapy (5FU/MMC) was administered in conjunction with radiation.[5,6] The five-year survival rate for patients receiving standard chemoradiation approaches 70%; however, 20%-40% experience grade 3-4 toxicity, and administration with MMC causes profound hematologic toxicity.

Androgen deprivation therapy (ADT) has been used in the management of prostate cancer for more than four decades. Initially, hormone therapy was given largely for palliation of symptomatic metastases. Following several randomized trials of patients with intermediate- to high-risk prostate cancer that demonstrated improvements in biochemical control and survival with the addition of ADT to external beam radiotherapy, there was a dramatic increase in the use of hormone therapy in the definitive setting. More recently, the safety of ADT has been questioned, as some studies have suggested an association of hormone therapy with increased cardiovascular morbidity and mortality. This is particularly worrisome in light of practice patterns that show ADT use extrapolated to situations for which there has been no proven benefit. In the setting of dose escalation with modern radiotherapy, in conjunction with the latest concerns about cardiovascular morbidity with ADT, the magnitude of expected benefit along with potential risks of ADT use must be carefully considered for each patient.

Adjuvant hormonal deprivation therapy is often administered long-term to patients with hormone receptor–positive cancers for primary prevention of breast cancer and secondary prevention of a recurrence.[1,2] This treatment modality is of particular importance to the elderly for two reasons: 1) the incidence of hormone-sensitive cancers (eg, prostate cancer and breast cancer) increases with age,[3] and 2) the systemic treatment regimens for elderly patients with hormone-responsive cancers are often limited to long-term hormonal deprivation therapy (HDT), most commonly androgen deprivation therapy for prostate cancer and aromatase inhibitor therapy for breast cancer, with chemotherapy often omitted.[2,4]

The incidence of metabolic syndrome is rapidly increasing. Metabolic syndrome is associated with elevated morbidity and mortality secondary to cardiovascular disease, insulin resistance, and hepatic dysfunction. A body of evidence has already implicated metabolic syndrome as a cancer risk factor; emerging evidence now suggests that cancer survivors themselves may be at risk for developing metabolic syndrome as a result of their anti-cancer therapy. Treatment of both breast cancer and prostate cancer often involves hormone-modifying agents that have been linked to features of metabolic syndrome. Androgen suppression in men with prostate cancer is associated with dyslipidemia, increasing risk of cardiovascular disease, and insulin resistance. Anti-estrogen therapy in women with breast cancer can affect lipid profiles, cardiovascular risk, and liver function. Similar findings have been noted in men with testicular cancer treated with chemotherapy. In addition, several emerging therapies, including mammalian target of rapamycin (mTOR) inhibitors and targeted kinase inhibitors, are increasingly associated with some features of metabolic syndrome. As the number of cancer survivors continues to grow, consideration of these factors and of the risk of metabolic syndrome will become increasingly important when choosing between therapy options and managing long-term follow-up.

Androgen deprivation therapy (ADT) has been shown to be beneficial in combination with radiotherapy (RT) vs RT alone in multiple phase III randomized trials treating patients with high-risk prostate cancer. Drs. Fang, Merrick, and Wallner have concisely summarized the data in Table 1 of their article. The Radiation Therapy Oncology Group trial RTOG 86-10 has demonstrated that as little as 4 months of ADT in combination with RT can delay the time to development of metastatic disease by up to 8 years, compared with RT alone.[1] What’s more, longer durations of ADT (ie, 28 to 36 months) are superior to shorter durations (4 to 6 months), as evidenced by the results of RTOG 92-02 and the European Organisation for Research and Treatment of Cancer trial EORTC 22961. Therefore, a long-term duration of ADT (ie, 24 to 36 months) is an accepted standard of care in combination with RT for patients with high-risk disease.

The role, timing, and clinical use of androgen deprivation therapy (ADT) in prostate cancer remain a controversial topic for clinicians. Drs. Fang, Merrick, and Wallner provide a compelling review of the clinical benefits and side effects of ADT in high-risk prostate cancer. The number of patients presenting with advanced disease remains significant despite the stage migration of prostate cancer during the PSA (prostate-specific antigen) era.

Prostate cancer is the second leading cause of cancer-related death among men in the United States.[1] Androgen deprivation therapy (ADT) is a common treatment for prostate cancer. ADT includes gonadotropin-releasing hormone (GnRH) agonists (leuprolide, goserelin, triptorelin), bilateral orchiectomy, and anti-androgen receptor blockers such as flutamide and bicalutamide. Several studies have now shown conflicting evidence that anti-androgen therapy may lead to increased cardiovascular morbidity and mortality.[2-5] None of these studies has provided conclusive evidence for causality or a direct link to cardiovascular disease, but they have proposed that therapy side-effects increase parameters that are similar to those of the metabolic syndrome.

The treatment of cancer of the anal canal has changed significantly over the past several decades. Although the abdominoperineal resection (APR) was the historical standard of care, a therapeutic paradigm shift occurred with the seminal work of Nigro, who reported that anal canal cancer could be treated with definitive chemoradiation, with APR reserved for salvage therapy only. This remains an attractive approach for patients and physicians alike and the standard of care in this disease. Now, nearly four decades later, a similar approach continues to be utilized, albeit with higher radiation doses; however, this strategy remains fraught with considerable treatment-related morbidities. With the advent of intensity-modulated radiation therapy (IMRT), many oncologists are beginning to utilize this technology in the treatment of anal cancer in order to decrease these toxicities while maintaining similar treatment efficacy. This article reviews the relevant literature leading up to the modern treatment of anal canal cancer, and discusses IMRT-related toxicity and disease-related outcomes in the context of outcomes of conventionally treated anal cancer.

Each year in the United States, more than 200,000 women are diagnosed with breast cancer, and 40,000 women die of the disease.[1] Approximately two-thirds of breast cancers are hormone receptor–positive, and medications that suppress estrogen are the cornerstone of adjuvant therapy for these tumors. Tamoxifen, a selective estrogen receptor modulator, was the first agent developed for this purpose and is still used widely in premenopausal women. Aromatase inhibitors (AIs), which prevent peripheral conversion of adrenal androgens into estrogen, have largely become the agents of choice for postmenopausal women. Current guidelines recommend that all postmenopausal women with hormone receptor–positive early-stage breast cancer who do not have a contraindication to AIs be treated with one of these agents, either as primary therapy or after 2 to 5 years of tamoxifen treatment as part of a cross-over strategy.[2] These recommendations are based on five large adjuvant trials that demonstrated a 3% to 4% absolute reduction in subsequent breast cancer events in patients who received an AI as part of adjuvant breast cancer treatment compared with patients treated with 5 years of tamoxifen alone.[3-7] However, it is notable that despite the lower rates of recurrence in these trials in the patients who received AIs, most studies have not demonstrated a survival advantage for AIs.