Prostate Cancer

The prostate cancer drug Provenge (sipuleucel-T) offers a moderate survival benefit to patients, according to an analysis performed by the U.S. Centers for Medicare and Medicaid Services. The analysis was undertaken as part of a CMS review initiated in July to determine whether to cover the cost of the therapy.

The article by Rove et al represents a comprehensive review of the recent clinical advances in the treatment of metastatic, castrate-refractory prostate cancer. The therapeutic armamentarium for the treatment of prostate cancer remains limited compared to other malignancies, such as breast cancer. It took approximately 14 years after mitoxantrone data emerged for us to see the approval of another chemotherapy agent, docetaxel. The successful outcome of recent clinical trials confirms that true advancement in prostate cancer treatment can be achieved by rational and rigorous clinical testing, but participation in prostate cancer clinical trials remains low, especially participation by African-American patients. Research study enrollment should be a high priority for those health care professionals who treat this disease.

Resistance to androgen deprivation is an ominous milestone in the natural history of metastatic prostate cancer:this disease state, now referred to as castration-refractory prostate cancer (CRPC), is historically associated with a median survival of less than two years. Until recently, only docetaxel (in combination with prednisone or estramustine) demonstrated a benefit in overall survival vs comparator therapy with mitoxantrone plus prednisone.[1,2] However, in the past year, compelling data in support of several promising new treatments for CRPC have been reported. The new data offer evidence-based treatment options, but also raise many questions for patient management and future clinical research.

Prostate cancer will be diagnosed in one of six men during their lifetimes, and a small portion of these will progress after primary and salvage therapies. For many years, there were few treatment options for these patients after routine hormonal maneuvers, and standard of care since the early 2000s has consisted primarily of docetaxel, which improved survival over the previous first-line therapy mitoxantrone. In recent years, however, new therapies have begun to emerge to treat this devastating form of prostate cancer. This review examines the mechanisms behind these therapeutics and the key trials seeking to validate their clinical use.

Amidst controversy, the FDA finally approved the controversial prostate cancer therapy. Hopes are high that Provenge represents the first in a long line of effective immunotherapeutics.

Two doctors, formerly with CMS, make a case for comparative effectiveness. Their paper is sure to spark heated debate within the prostate cancer community--as always, never a dull moment in prostate cancer.

The threshold for physicians to accept worthiness of chemoprevention with 5-α reductase inhibitors remains high.

Cabazitaxel is a microtubule inhibitor in the taxane class. It is made from a yew needle precursor using a semisynthetic process. It binds to free tubulin, which is used during mitosis to form two daughter cells.

The brothers of men with prostate cancer face a higher disease risk because of increased diagnostic activity, and not necessarily because they carry a genetic mutation that increases risk of the disease, according to a Swedish study.

New studies show dramatic results in overall and progression-free survival, but not all patients will benefit from aggressive treatment.

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.

A New England Journal of Medicine editorial by Dan L. Longo, MD, called the ability of Provenge to prolong the survival in prostate cancer patients without having any measurable effect on the tumor “surprising” and “hard to understand.”

Prostate cancer is one of the leading causes of death from malignant disease among men in the developed world. The extent of benefit and harm with widespread PSA screening is under continuous debate.

This article defines the biochemical recurrence of prostate cancer, distinguish SRT from ART, outline the evidence for SRT, and makes recommendations with regard to radiotherapy volume and dose.

Despite the common use of postoperative radiotherapy (RT) in patients managed initially with radical prostatectomy (RP), a number of questions remain. Raldow and colleagues build their arguments around three randomized trials that indicated a significant benefit of immediate adjuvant radiotherapy in patients with high-risk features.

In their article, Raldow et al provide an excellent summary of the issues surrounding the use of salvage radiotherapy for a post-prostatectomy recurrence. For practicing clinicians, the pressing issue is how to appropriately select patients for treatment with salvage radiotherapy.

Cancer survival notwithstanding, patients must still be encouraged to maintain a healthy lifestyle to help avoid progression.

The European Commission (EC) has granted marketing authorization for the RANK ligand inhibitor denosumab (Prolia) for treatment of osteoporosis in postmenopausal women at increased risk of fractures, and for treatment of bone loss associated with hormone ablation in men with prostate cancer at increased risk of fractures. The European approval of Prolia marks its first approval worldwide. Amgen, the manufacturer of Prolia, announced the EC authorization on May 28, 2010.

Once PSA kinetics were thought to be a good way to predict which patients with early prostate cancer were at risk of progression. Now they're not. Even those who had the most hope for these biomarkers have evidence of their unreliability for this purpose.

Trelstar (22.5 mg triptorelin pamoate) has received FDA marketing approval as a twice-yearly intramuscular gonadotropin-releasing hormone (GnRH) agonist.

Cabazitaxel, an investigational taxane, significantly extended survival among prostate cancer patients whose disease had progressed despite hormone therapy.

The technique provides a new and continuously evolving tool in oncologic imaging for lesion detection, characterization, and therapy assessment.

ONCOLOGY board member Judd Moul, MD, told the CancerNetwork blog that there will be several controversial pro-con debates featured at this year’s Society of Urologic Oncology (SUO) meeting, May 29th in San Francisco. Dr. Moul will moderate a pro-con debate about the effectiveness of PSA screening during a session titled, Prostate Cancer I – Screening: Lessons from the PLCO and ESRPC Randomized Trials. Stand by for exclusive interviews and podcasts…

Almost 3 years after a controversial FDA denial, Provenge was approved, making it the first autologous cellular immunotherapy for prostate cancer. One pressing question about Provenge is how much its maker, the biotech company, Dendreon, would charge for its newly approved drug.

A new study supports previous findings that finasteride prevents prostate cancer. However, like much research in prostate cancer, the study leaves us with as many questions as answers.