Tuesday, May 28, 2013

New AUA Guideline for Castration-Resistant Prostate Cancer

The American Urological Association (AUA) has issued a new guideline (http://www.auanet.org/education/guidelines/castration-resistant-prostate-cancer.cfm) for the management of castration-resistant prostate cancer (CRPC) that provides a "rational basis" for treatment decisions.
Those decisions are now "complex" because a group of treatment options for metastatic disease has emerged in a short period of time, according to a press release issued at AUA 2013 Annual Scientific Meeting, held in San Diego, California.
The treatment options in metastatic CRPC (mCRPC) include 4 new therapies that have been approved since 2010: sipuleucel-T (Provenge, Dendreon), cabazitaxel (Jevtana, sanofi-aventis), abiraterone (Zytiga, Janssen), and enzalutamide (Xtandi, Astellas/Medivation). These therapies, along with docetaxel (approved in 2004), have all been shown to improve overall survival in metastatic disease.
"Prior to 2004, once patients failed primary androgen deprivation, treatments were administered solely for palliation," write the guideline authors, led by Michael S. Cookson, MD, from Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.
The guidelines are much needed, according to a clinician not involved with their writing. "There is a lack of clarity as to the best method for treating castration-resistant prostate cancer," said Willie Underwood III, MD, MPH, from the Roswell Park Cancer Institute in Buffalo, New York.
The guidance is especially important given the publicity that has accompanied the new therapies, as well as their cost, he told Medscape Medical News in an interview. "When a drug comes out with a lot of hype, every patient wants that drug."
A large part of the new guideline is recommendations for 6 different types of patients. These "index" patients represent the most common clinical scenarios in men whose prostate cancer is not responsive to traditional androgen-deprivation therapy.
The profiles of the index patients comprise symptoms, performance status, the presence or absence of metastases, and whether or not docetaxel has been administered.
The guideline authors acknowledge that treatment is rapidly changing, and advise clinicians to use it in conjunction with the "current literature" and an individual patient's treatment goals.
The following are the index patients and the associated recommendations.
Index Patient 1: Asymptomatic Nonmetastatic CRPC
The typical patient has a rising prostate-specific antigen (PSA) level and no radiologic evidence of metastatic prostate cancer. He is also required to have castrate levels of testosterone (less than 50 ng/mL).
Treatment recommendations
Observation with continued androgen deprivation
First-generation antiandrogens (flutamide, bicalutamide, and nilutamide) or first-generation androgen-synthesis inhibitors (ketoconazole plus steroid) to patients unwilling to accept observation
No treatment has been shown to improve overall survival in these men. "Since all agents have potential side effects...we must first do no harm," write the authors.

Index Patient 2: Asymptomatic or Minimally Symptomatic mCRPC Without Previous Docetaxel Chemotherapy
These patients have "a rising PSA in the setting of castrate levels of testosterone" and metastatic disease documented on radiographic imaging.
Treatment recommendations
Abiraterone plus prednisone, docetaxel, or sipuleucel-T
First-generation antiandrogen therapy or ketoconazole plus steroid or observation to patients who do not want or cannot have one of the standard therapies
The 3 standard therapies are approved by the US Food and Drug Administration for this indication and improved overall survival in randomized clinical trials. There are no direct comparison studies to inform optimal sequencing. "As a general principle, it is preferable to give the least toxic agent first," the authors note.

Index Patient 3: Symptomatic mCRPC With Good Performance Status and No Previous Chemotherapy
These patients have a rising PSA level in the setting of castrate levels of testosterone. Their symptoms should be related to prostate cancer alone (and not other conditions), and might include pain.
Treatment recommendations
Abiraterone plus prednisone
Ketoconazole plus steroid, mitoxantrone, or radionuclide therapy for patients who do not want or cannot have one of the standard therapies
Sipuleucel-T immunotherapy is not recommended in symptomatic disease, the authors note.

Index Patient 4: Symptomatic mCRPC With Poor Performance Status and No Previous Docetaxel Chemotherapy
Clinical trials have generally excluded patients with a poor performance status (ECOG 3 or 4); as a result, data guiding their management are extrapolated from randomized trials of healthier patients.
Treatment recommendations
Abiraterone plus prednisone
Ketoconazole plus steroid or radionuclide therapy to patients who are unable or unwilling to receive abiraterone plus prednisone
Docetaxel or mitoxantrone chemotherapy in select cases, specifically when performance status is directly related to the cancer

Patient 5: Symptomatic mCRPC With Good Performance Status and Previous Docetaxel Chemotherapy
A focus of therapy should be to maintain the excellent performance status without significant toxicity from additional therapy.
Treatment recommendations
Abiraterone plus prednisone, cabazitaxel, or enzalutamide
If the patient received abiraterone plus prednisone prior to docetaxel chemotherapy, offer cabazitaxel or enzalutamide
Ketoconazole plus steroid if abiraterone plus prednisone, cabazitaxel, or enzalutamide is unavailable
Retreatment with docetaxel for patients who were benefiting from but discontinued treatment with docetaxel because of reversible adverse effects
Abiraterone plus prednisone and enzalutamide appear to provide clinical benefit equivalent to (if not superior to) additional intravenous chemotherapy with an agent such as cabazitaxel. These 2 therapies have "significantly less acute toxicity and no apparent cumulative toxicity" over prolonged periods, say the authors.

Index Patient 6: Symptomatic mCRPC With Poor Performance Status and Previous Docetaxel Chemotherapy
"Treatment given in the last months of life may delay access to end-of-life care, increase costs, and add unnecessary symptom management. Patients with poor performance status (ECOG 3 or 4) should not be offered further treatment," write the authors.
Treatment recommendations
Palliative care
For selected patients, offer treatment with abiraterone plus prednisone, enzalutamide, ketoconazole plus steroid, or radionuclide therapy
There is insufficient evidence demonstrating a treatment benefit in this patient population.

Because the skeletal system is the most common site for prostate cancer metastasis, the guideline also makes recommendations regarding bone health.
Bone Health
Treatment recommendations
Offer preventative treatment (e.g., supplemental calcium, vitamin D) for fractures
Choose either denosumab or zoledronic acid as preventative treatment for skeletal-related events

"Prostate cancer deaths are typically the result of mCRPC, a painful disease," said Dr. Cookson in a press statement. "In recent years, a number of new treatments and therapeutic agents have entered the market that have been shown to minimize adverse effects and pain and prolong survival in some patients, but the fact remains that mCRPC is the terminal stage of prostate cancer."

Saturday, May 25, 2013

Marijuana May Lower Bladder Cancer Risk

SAN DIEGO, California — Smoking marijuana might decrease the smoker's risk for bladder cancer, a new study shows.
Retrospectively analyzing a large database of patients, researchers at Kaiser Permanente in California found that patients who reported cannabis use were 45% less likely to be diagnosed with bladder cancer than patients who did not smoke at all.
"It's very exciting because bladder cancer is hard to treat," said Anil Thomas, MD, a urologist at the Southern California Permanente Medical Group. But he cautioned that the study does not prove that smoking marijuana prevents bladder cancer, and more research is needed to explore the connection.
Dr. Thomas presented the study here at the American Urological Association 2013 Annual Scientific Meeting.
"We know that tobacco smoking is the best established risk factor for bladder cancer," Dr. Thomas told reporters attending a news conference. "But to date, there are no epidemiologic studies accurately characterizing the association between cannabis use and bladder cancer."
To fill that gap, Dr. Thomas and his colleagues analyzed a survey of 82,050 men from Northern and Southern California Kaiser Permanente, a health maintenance organization, conducted in 2002 and 2003.
The participants were aged 45 to 69 years.
In all, 41% reported using cannabis, 57% reported using tobacco, and 27% reported using both.
Distribution of Respondents by Extent of Cannabis Consumption
1–2 times
3–10 times
11–99 times
100–499 times
More than 499 times

Over the subsequent 11 years, more patients who reported no cannabis use than who reported use developed incident bladder tumors (0.4% vs 0.3%). The difference was statistically significant (P = .048).
However, patients who smoked only tobacco had an increased risk for bladder cancer, and those who smoked both tobacco and marijuana had about the same risk as those who smoked neither.
This might explain why previous studies have not uncovered any protective effects of marijuana, Dr. Thomas said. To see this effect, it's necessary to separate out the marijuana smokers who do not smoke tobacco.
Discussion moderator Kevin McVary, MD, chair of urology at Southern Illinois University in Springfield, asked if there were similar databases that could be used to verify these results. Dr. Thomas said he is not aware of any.
Dr. Thomas told Medscape Medical News that he first got interested in exploring this topic while doing some laboratory work in which he exposed prostate cancer cells and bladder cancer cells to cannabis.
"The prostate cancer cells did not show an effect and the bladder cancer cells were devastated," he said.
Some other research has suggested that cannabis might kill other types of cancer cells as well, he said. "I don't think the full mechanism is known."
Dr. Thomas and Dr. McVary have disclosed no relevant financial relationships.
American Urological Association (AUA) 2013 Annual Scientific Meeting. Presented May 6, 2013.

Monday, May 6, 2013

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