Genitourinary Cancers

As a clinician and researcher in the prostate cancer field, I have been hearing that prostate cancer is “20 years behind” breast cancer now for the last 25 years!

For many years, the results of large randomized clinical trials of cancer vaccines have not been good.

Prostate cancer is the second-leading cause of death in men in the United States; more than 217,730 new cases were expected to be diagnosed in 2010.[1] Although the majority of patients with advanced prostate cancer have an initial response to androgen deprivation, essentially all patients eventually progress to a castration-resistant state, manifested by rising levels of prostate-specific antigen (PSA),

In a study reported in Nature online on February 2, researchers describe a four-gene signature that was more accurate than the standard Gleason score test in predicting which patients would die from metastatic spread of their prostate cancer.

The GlaxoSmithKline (GSK) drug Avodart (dutasteride), already approved for treatment in men with enlarged prostate glands, has been rejected by the FDA for the additional indication of reducing the risk of prostate cancer.

Adding chemotherapy to radiation therapy for muscle invasive bladder cancer may allow up to 67% of patients to be free of disease two years post-treatment, according to a study out of the UK. In addition, this treatment combination may offer a significant number of patients a better quality of life by avoiding surgery.

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.

The review by Rampersaud and colleagues provides an excellent summary of the scientific rationale for using hyperthermia to treat cancer and of the current status of combinations of hyperthermia and chemotherapy or radiotherapy. In view of the demonstrated efficacy of the combination of intravescial hyperthermia and mitomycin C (MMC) therapy in preventing the progression and recurrence of non–muscle-invading bladder cancer (NMIBC) in several clinical trials, Rampersaud and colleagues advocate additional studies to further optimize the delivery of hyperthermia and to delineate its clinical utility in this disease.

Modern cancer care is characterized by a focus on organ-sparing multi-modal treatments. In the case of non–muscle-invasive bladder cancer this is particularly true; treatment is focused on reducing the frequency of low-risk recurrences and preventing high-risk progression. Deep regional hyperthermia is an oncologic therapeutic modality that can help achieve these two goals. The combination of hyperthermia with chemotherapy and radiotherapy has improved patient outcomes in several tumor types. In this review, we highlight the biology of therapeutic fever-range hyperthermia, discuss how hyperthermia is administered and dosed, demonstrate how heat can be added to other treatment regimens, and summarize the data supporting the role of hyperthermia in the management of bladder cancer.

Bladder cancer is the fourth most common cancer (excluding skin cancer) in the United States and ranks eighth as a cause of death from cancer among men; there will be an estimated 70,530 new cases and 14,680 cancer-related deaths in the United States in 2010.[1] Of new cases, 70% to 80% present with non–muscle-invasive bladder cancer (NMIBC). Despite endoscopic and intravesical treatments with curative intent, 50% to 70% of these cancers recur, usually within 5 years, and 10% to 30% progress to muscle-invasive disease, in the majority of cases as high-grade lesions.[2,3] Bladder cancer poses a significant economic burden due to the cost of the lifetime need for surveillance, the need to treat recurrent tumors, and the cost of complications associated with treatment. Medicare estimates have ranked bladder cancer treatment the seventh costliest among cancers, with a 5-year net cost of approximately one billion dollars.[4]

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.

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.

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 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.

A 36-year-old male with a history of cryptorchidism of the right side, treated with orchidopexy at the age of 4, presented with bilateral testicular swelling. Investigations included laboratory workup, ultrasound of both testes, as well as CT-scan of the chest, abdomen, and pelvis. Initial treatment was bilateral orchiectomy.

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.

Listen to internationally regarded oncologist and clinical investigator, Robert J. Motzer, MD, attending physician at Memorial Sloan-Kettering Cancer Center, discuss the past, present, and future trends in renal cell carcinoma.

In this exclusive ASCO podcast, Andrew J. Armstrong, MD, ScM, Assistant Professor of Medicine and Surgery Duke Comprehensive Cancer Center, Departments of Medicine and Surgery, Divisions of Medical Oncology and Urology, addressed the vexing clinical issue of chemotherapy’s limited effectiveness in advanced renal cell carcinoma.

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.

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.

Renal cell carcinoma represents 3% of all cancer cases but has a significant death rate associated with it: It’s estimated that there will be 60,000 new cases this year and 16,000 deaths from kidney cancer. The risk factors associated with kidney cancer include smoking, obesity, hypertension, and some occupational exposure.

A 56-year-old woman was referred to our institution for a left nephroureterectomy after the diagnoses of a nonfunctioning left kidney and noninvasive papillary urothelial carcinoma of the distal left ureter (Ta grade 1). Following the procedure, surveillance cystoscopy and computed tomography (CT) scan of the abdomen and pelvis demonstrated a large bladder tumor with pan-urothelial extension.

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Non-Hodgkin’s Lymphomas (NHL) have been updated to include ofatumumab (Arzerra) and romidepsin (Istodax). Ofatumumab was added to the NCCN Guidelines as a treatment option for relapsed/refractory disease in patients with chronic lymphocytic leukemia, with and without a 17p deletion. In addition, the updated guidelines include romidepsin as a systemic treatment option for patients with mycosis fungoides and Szary syndrome.

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.

GlaxoSmithKline has received FDA approval for pazopanib (Votrient) for the treatment of patients with advanced renal cell carcinoma. The FDA’s approval of the angiogenesis inhibitor was based on data from a phase III clinical trial, which demonstrated that pazopanib reduced the risk of tumor progression or death by 54% compared with placebo and regardless of prior treatment.