Genitourinary Cancers

The article by Polascik and coauthors provides a timely synopsis of modern technologic advances in prostate cryoablation and a review of the rationale for and experience with targeted prostate treatments. Prostate cryoablation has a storied past, which can be briefly summarized as high excitement followed by near-complete abandonment. Fortunately, a few practitioners improved the technique and incorporated new technologies allowing for its resurrection.

Wyeth Pharmaceuticals recently announced the initiation of the INTORACT (INvestigation of TORisel and Avastin Combination Therapy) study, a worldwide randomized, open-label, phase IIIB study comparing temsirolimus (Torisel) plus bevacizumab (Avastin) vs bevacizumab plus interferon-alfa for first-line treatment of patients with advanced renal cell carcinoma (RCC). Wyeth Research is conducting the INTORACT study with the support and assistance of Roche and Genentech

CHICAGO-The combination of custir-sen sodium (OGX-011, OncoGenex Technologies Inc), an investigational agent, with docetaxel (Taxotere) or mitoxantrone has acceptable toxicity in patients with hormone-refractory prostate cancer who have experienced a failure of first-line docetaxel-based chemotherapy, investigators reported at ASCO 2008 (abstract 5002). Efficacy outcomes were somewhat better with the custirsen/docetaxel combination.

A multicenter study has found that the experimental targeted therapy everolimus (Cetican, RAD001) delays cancer progression in patients with metastatic kidney cancer that has progressed despite treatment with other targeted therapies. Lead author Robert J. Motzer, md, attending physician at Memorial Sloan-­Kettering Cancer Center, presented the results at the ASCO meeting (abstract LBA5026).

The first randomized trial to evaluate the long-term outcome of treatment with a single dose of chemotherapy for early-stage testicular tumors has found that the approach is safe, effective, and less toxic compared to radiation therapy, the current standard of care. The study, the largest ever in testicular cancer, also showed that after 5 years, patients receiving chemotherapy had a decreased risk of developing a second tumor in the other testicle, though longer follow-up is needed. The data were presented by R.T. Oliver, md, professor emeritus of medical oncology at St. Bartholomew’s Hospital in London and the study’s lead author, at the ASCO plenary session (abstract 1).

External-beam radiation is a highly effective curative treatment option for men with localized prostate cancer.[1,2] Over the past several decades, efforts have been made to improve the “therapeutic ratio” of radiation by increasing dose to improve cure rates without causing a substantial increase in side effects. Due to its potential to create superior dose distributions, proton therapy is considered by many to be the best available form of external radiation therapy. Here we will critically examine the evidence supporting the use of protons in the treatment of prostate cancer.

MILAN-Some men with nonseminoma germ cell tumor (NSGCT) testicular cancer have a normalization of tumor markers and minimal or no residual masses in the retroperitoneum after chemotherapy. What then? Should all of them undergo retroperitoneal lymph node dissection (RPLND) to be on the safe side, or should the procedure be reserved for selected cases? Leading researchers in urology debated this topic at the 23rd Annual Congress of the European Association of Urology (plenary session 1).

Financial pressures from Medicare reimbursement changes may have caused physicians to switch from providing hormonal-induced castration to providing surgical castration for men with prostate cancer. That is the finding of a new study published in the May 15 issue of CANCER. The study suggests that factors other than evidence-based medicine may have a significant influence on treatment decisions.

NEW YORK-Antigenics Inc.’s personalized cancer vaccine Oncophage (vitespen) has received its first government approval.

A drug proven effective in a large randomized prostate cancer prevention trial is rarely used for that indication. ONI explores the economic and clinical reasons underlying the agent's lack of use.

Drs. Rini and Bukowski do an excellent job of updating and commenting on the rapidly evolving field of therapy for metastatic renal cell carcinoma (RCC).

An independent data monitoring committee stopped a phase III clinical trial of the investigational mTOR inhibitor everolimus (RAD001) after interim results showed significantly better progression-free survival in patients with advanced kidney cancer who received the drug, compared with placebo.

Researchers have reported finding a blood biomarker that enables close to 98% accuracy in predicting the spread of prostate cancer to regional lymph nodes. Their study is published in the March 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research. The new blood test measures levels of endoglin, a plasma biomarker that has been previously shown to predict the spread of colon and breast cancer.

In the November 30, 2007, issue of ­ONCOLOGY, Dr. Tony S. Quang and colleagues have raised some very important and relevant issues regarding the costs and benefits of new technology in the treatment of prostate cancer ("Technologic Evolution in the Treatment of Prostate Cancer: Clinical, Financial, and Legal Implications for Managed Care Organizations," ONCOLOGY 21[13]:1598-1604, 2007).

In a group of 2,893 Swedish men with prostate cancer, five gene variants plus family history accounted for 46% of cases

The use of high-intensity focused ultrasound (HIFU) as a method for ablation of a localized tumor growth is not new. Several attempts have been made to apply the principles of HIFU to the treatment of pelvic, brain, and gastrointestinal tumors. However, only in the past decade has our understanding of the basic principles of HIFU allowed us to further exploit its application as a radical and truly noninvasive, intent-to-treat, ablative method for treating organ-confined prostate cancer. Prostate cancer remains an elusive disease, with many questions surrounding its natural history and the selection of appropriate patients for treatment yet to be answered. HIFU may play a crucial role in our search for an efficacious and safe primary treatment for localized prostate cancer. Its noninvasive and unlimited repeatability potential is appealing and unique; however, long-term results from controlled studies are needed before we embrace this new technology. Furthermore, a better understanding of HIFU's clinical limitations is vital before this treatment modality can be recommended to patients who are not involved in well-designed clinical studies. This review summarizes current knowledge about the basic principles of HIFU and its reported efficacy and morbidity in clinical series published since 2000.

The use of high-intensity focused ultrasound (HIFU) as a method for ablation of a localized tumor growth is not new. Several attempts have been made to apply the principles of HIFU to the treatment of pelvic, brain, and gastrointestinal tumors. However, only in the past decade has our understanding of the basic principles of HIFU allowed us to further exploit its application as a radical and truly noninvasive, intent-to-treat, ablative method for treating organ-confined prostate cancer. Prostate cancer remains an elusive disease, with many questions surrounding its natural history and the selection of appropriate patients for treatment yet to be answered. HIFU may play a crucial role in our search for an efficacious and safe primary treatment for localized prostate cancer. Its noninvasive and unlimited repeatability potential is appealing and unique; however, long-term results from controlled studies are needed before we embrace this new technology. Furthermore, a better understanding of HIFU's clinical limitations is vital before this treatment modality can be recommended to patients who are not involved in well-designed clinical studies. This review summarizes current knowledge about the basic principles of HIFU and its reported efficacy and morbidity in clinical series published since 2000.

Eating a concentrated extract of freeze-dried broccoli sprouts might inhibit bladder cancer by delivering a protective factor right where the bladder is most at risk.

Occult distant micrometastasis at the time of radical cystectomy leads predominantly to distant failures in patients with locally advanced muscle-invasive transitional cell carcinoma of the bladder. Cisplatin-based combination chemotherapy enhances survival in patients with metastatic urothelial cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power. However, randomized clinical trials have demonstrated a survival benefit for neoadjvuant cisplatin-based combination chemotherapy, which should be considered a standard of care. In addition, neoadjuvant therapy may assist in the rapid development of novel systemic therapy regimens, since pathologic complete remission appears to be a powerful prognostic factor for long-term outcomes. Patients who are either unfit for or refuse radical cystectomy may benefit from neoadjuvant chemotherapy with or without radiation to enable bladder preservation.

federal Centers for Medicare and Medicaid Services (CMS) have increased their hospital outpatient and ambulatory surgical center reimbursement rates for cryoablation treatments for prostate cancer

Occult distant micrometastasis at the time of radical cystectomy leads predominantly to distant failures in patients with locally advanced muscle-invasive transitional cell carcinoma of the bladder. Cisplatin-based combination chemotherapy enhances survival in patients with metastatic urothelial cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power. However, randomized clinical trials have demonstrated a survival benefit for neoadjvuant cisplatin-based combination chemotherapy, which should be considered a standard of care. In addition, neoadjuvant therapy may assist in the rapid development of novel systemic therapy regimens, since pathologic complete remission appears to be a powerful prognostic factor for long-term outcomes. Patients who are either unfit for or refuse radical cystectomy may benefit from neoadjuvant chemotherapy with or without radiation to enable bladder preservation.

Occult distant micrometastasis at the time of radical cystectomy leads predominantly to distant failures in patients with locally advanced muscle-invasive transitional cell carcinoma of the bladder. Cisplatin-based combination chemotherapy enhances survival in patients with metastatic urothelial cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power. However, randomized clinical trials have demonstrated a survival benefit for neoadjvuant cisplatin-based combination chemotherapy, which should be considered a standard of care. In addition, neoadjuvant therapy may assist in the rapid development of novel systemic therapy regimens, since pathologic complete remission appears to be a powerful prognostic factor for long-term outcomes. Patients who are either unfit for or refuse radical cystectomy may benefit from neoadjuvant chemotherapy with or without radiation to enable bladder preservation.

past decade has witnessed a host of technologic improvements in prostate cancer therapy. The three major modalities offered in most managed care plans include radical prostatectomy, external-beam radiation therapy (EBRT), and interstitial brachytherapy (seed implant). Continued technologic advancement has led to incremental improvements in the safety and effectiveness of each modality. However, these improvements have led to a significant increase in the cost of treatment.

Preliminary phase I trial data suggest that the combination of recombinant IL-21 and sorafenib (Nexavar) is well tolerated in patients with metastatic renal cell carcinoma and has promising anti-tumor activity, lead investigator John A. Thompson, MD, and his colleagues reported

Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in two main clinical settings: (1) rising PSA to signal failed initial local therapy and (2) rising PSA in the setting of early hormone-refractory prostate cancer prior to documented clinical metastases. Most urologists and radiation oncologists are very familiar with the initial very common clinical scenario, commonly called "biochemical recurrence." In fact, up to 70,000 men each year will have a PSA-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based upon the patient's risk of progression and the likelihood of success and the risks involved with the therapy. It is unknown how many men per year progress with rising PSA while on hormonal therapy without documented metastases. This rising PSA disease state is sometimes called, "PSA-only hormone-refractory prostate cancer." As in the setting of initial biochemical recurrence, evidence-based treatment options are limited, and taking a risk-stratified approach is justified. In this article, we will explore these prostate cancer disease states with an emphasis on practical, clinically applicable approaches.

Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in two main clinical settings: (1) rising PSA to signal failed initial local therapy and (2) rising PSA in the setting of early hormone-refractory prostate cancer prior to documented clinical metastases. Most urologists and radiation oncologists are very familiar with the initial very common clinical scenario, commonly called "biochemical recurrence." In fact, up to 70,000 men each year will have a PSA-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based upon the patient's risk of progression and the likelihood of success and the risks involved with the therapy. It is unknown how many men per year progress with rising PSA while on hormonal therapy without documented metastases. This rising PSA disease state is sometimes called, "PSA-only hormone-refractory prostate cancer." As in the setting of initial biochemical recurrence, evidence-based treatment options are limited, and taking a risk-stratified approach is justified. In this article, we will explore these prostate cancer disease states with an emphasis on practical, clinically applicable approaches.

Sunitinib lowers PSA in some advanced prostate cancer pts

Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in two main clinical settings: (1) rising PSA to signal failed initial local therapy and (2) rising PSA in the setting of early hormone-refractory prostate cancer prior to documented clinical metastases. Most urologists and radiation oncologists are very familiar with the initial very common clinical scenario, commonly called "biochemical recurrence." In fact, up to 70,000 men each year will have a PSA-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based upon the patient's risk of progression and the likelihood of success and the risks involved with the therapy. It is unknown how many men per year progress with rising PSA while on hormonal therapy without documented metastases. This rising PSA disease state is sometimes called, "PSA-only hormone-refractory prostate cancer." As in the setting of initial biochemical recurrence, evidence-based treatment options are limited, and taking a risk-stratified approach is justified. In this article, we will explore these prostate cancer disease states with an emphasis on practical, clinically applicable approaches.

High-dose combination chemotherapy followed by autologous peripheral-blood stem cell transplant produced durable remissions in metastatic testicular cancer patients who relapsed or failed to respond to traditional therapy

The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.