Prostate Cancer

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.

Mismanaged therapy at one institution has dealt a blow to the field, but practitioners explain why the technique remains worthwhile.

One of the largest clinical trials classifies which patients will benefit most from androgen deprivation therapy paired with radiotherapy.

Most men who have had radical prostatectomy can look forward to at least 15 years free from prostate cancer. But which patients are likely to see their PSA levels double within nine months, and therefore have high risk of recurrence? Oncologists are calling for new ways to predic, and researchers are on the case.

Prostate cancer patients administered high doses of proton-beam therapy appear to have a markedly reduced risk of disease recurrence when compared with other low-risk patients treated with conventional radiation therapy, according to two recent studies.

In order for a new treatment modality to be considered efficacious, it needs to be evaluated by acceptable criteria and demonstrate an improvement on the natural course of the disease.

Over 40 million men and women in the United States have osteoporosis and low bone mineral density (BMD), placing them at risk for adverse skeletal events such as fractures and their sequelae. There are over 12 million cancer survivors in this country. Of these, 22% were diagnosed with breast cancer and 17% with prostate cancer.[1,2] Because cancer therapies can adversely influence bone health, these survivors are at particular risk for skeletal complications. Cancer therapies associated with bone loss include hormone deprivation therapies such as aromatase inhibitors, ablative surgical procedures that induce hypogonadal states, and premature menopause induced by chemotherapy.[3,4]

The first major study to address the cardiovascular adverse effects of endocrine therapy for prostate cancer could change attitudes toward treatment options because testosterone deprivation may have more impact on the patient’s life than it does on the androgen receptor.

Findings of a study by researchers in Italy suggest C-11 choline PET/CT could diagnose prostate cancer recurrence sooner than transrectal ultrasound, CT, MRI, or bone scintigraphy in patients who have undergone radical prostatectomy.

Astellas has partnered with Medivation to co-develop and market the oral anti-androgen, MDV3100. In September, Medivation enrolled patients in the phase III AFFIRM trial, which is evaluating MDV3100 in 1,200 men with castration-resistant prostate cancer who were previously treated with docetaxel (Doxil) chemotherapy.

Dr. Otis W. Brawley took a courageous stand late last week, one he has taken many times before, but which had until then gone all but unnoticed. Responding to a Journal of the American Medical Association article detailing the scientific and medical limitations of breast and prostate screening, the chief medical officer of the American Cancer Society acknowledged that “in the case of some screening for some cancers, modern medicine has overpromised.”

The comparison of brachytherapy and surgery may be done on several levels. This review focuses the comparison on toxicity, the “soft” endpoints of biochemical relapse-free survival and clinical relapse-free survival, and the “hard” endpoint of prostate cancer–specific mortality.