Wednesday, April 25, 2012

Robot Assisted Prostate Cancer Surgery Compares Favorably

Outcomes from use of a robot to assist surgeons in removal of a cancerous prostate are at least as good, if not better, than the other two techniques used for a radical prostatectomy -- open or laparoscopic surgery -- according to a large meta analysis led by researchers at NewYork-Presbyterian/Weill Cornell.

The study, published February 24 online in European Urology, should help resolve some of the controversy regarding use of the robotic option, known as robot assisted laparoscopic radical prostatectomy (RALP), says the study's lead author, Dr. Ashutosh Tewari, director of the Lefrak Center for Robotic Surgery and director of the Prostate Cancer Institute at New York-Presbyterian Hospital/Weill Cornell Medical Center.

"There is a lot of debate about the best way to remove a cancerous prostate gland," says Dr. Tewari, who is also the Ronald P. Lynch Professor of Urologic Oncology and professor of urology and public health at Weill Cornell Medical College. "Since the robotic technology is expensive, the patient benefits often get intertwined with the societal costs. It is clear, however, that robotic surgery is the most popular surgical modality today. This study represents the largest ever systematic review of patient outcomes comparing robotic-assisted, laparoscopic and open radical prostatectomy.

By analyzing 400 original research articles -- all that have been published to date on the three methods -- Dr. Tewari and his colleagues concluded that RALP is more effective than a pure laparoscopic approach and comparable to an open surgical approach in completely removing cancer from the body. Positive surgical margins, a measure of oncological efficacy, were lower in patients receiving robotic radical prostatectomy as compared to those undergoing laparoscopic prostatectomy.

The researchers also found that robot assisted surgery had fewer intraoperative and perioperative complication rates when compared to both laparoscopic and open approaches. In addition, robotic showed both less intraoperative blood loss and less blood transfusions as compared to open surgery.

The meta analysis included treatment information on 286,876 patients, representing the largest compilation of radical prostatectomy patients to date.

"Understanding the best method to remove the prostate matters," Dr. Tewari says, "because prostate cancer is the most common diagnosed cancer and the second most common cause of cancer death for men in developed countries."

But given the nature of the study, Dr. Tewari says he cannot recommend one surgical approach over another. He emphasizes that surgical approaches need to be adjusted for the technique and experience of the surgeon. Many studies have shown that surgical experience is an independent predictor for outcomes, far beyond the approach alone.

"This paper is innovative in its attempt to unpack the outcomes data, in a systematic way, surrounding the three surgical modalities for prostate cancer treatment, but the data we used were not standardized -- outcome measures differed between studies," he says. "Still I believe the results are meaningful in that it shows RALP has at least as good outcomes as the other methods."

Challenges of Randomized Studies for Prostate Surgery

The three forms of surgery studied are "open radical" in which the prostate is removed via an abdominal incision in the belly button or pubic bone; laparoscopic prostatectomy that requires several small minimally invasive "keyhole" incisions in the abdomen, and robotic surgery, which is a form of laparoscopic surgery. RALP is done through keyholes with the aid of robotic arms that eliminate hand tremor as well as advanced optics that magnify the prostate and surrounding nerves in three-dimensions.

"It is hard to accrue patients for randomized studies. We have an ongoing study open at our institution, investigating the quality of life differences between robotic and open radical prostatectomy. This is designed as a randomized controlled study," he says. "But no one has enrolled because they did not want to be randomized to a treatment they don't prefer. Patients often come, especially to prostate cancer specialists, self-selecting for a particular treatment modality."

So Dr. Tewari and Peter Wiklund, M.D., of Sweden's Karolinska University Hospital, developed a study that examined all of the peer-reviewed studies published on any of the three techniques.

This ambitious effort was aimed at understanding the short-term (30 day) outcomes of the three surgical techniques. Given the short time frame, the meta analysis did not compare outcomes for urinary continence or sexual potency.

The researchers determined that complications and mortality were low for all three methods, suggesting that radical prostatectomy is a safe procedure.

Significant differences found were in the lower positive surgical margin (PSM) rates for RALP compared with laparoscopic surgery and lower intra operative and perioperative complications for RALP in comparison to other modalities. "PSM rates are important because they represent the effectiveness by which cancer is removed," Dr. Tewari says. "The RALP PSM rate was as good as open surgery," he adds.

The researchers also found that both laparoscopic and robotic surgery patients experienced lower rates of blood loss and transfusions and a shorter hospital stay compared with patients who had traditional surgery. Other measures, such as rates of readmission, reoperation, and complications, seemed to favor RALP, the researchers say.

"We would love to be able to directly compare the three prostatectomy surgical techniques, but that may not happen," Dr. Tewari says. "This study is the first to provide an important -- and much needed -- analysis of the short term benefits and risks between curative surgeries that many men rely on."

Oregano Kills Prostate Cancer Cells

Oregano, the common pizza and pasta seasoning herb, has long been known to possess a variety of beneficial health effects, but a new study by researchers at Long Island University (LIU) indicates that an ingredient of this spice could potentially be used to treat prostate cancer, the second leading cause of cancer death in American men.

Prostate cancer is a type of cancer that starts in the prostate gland and usually occurs in older men. Recent data shows that about 1 in 36 men will die of prostate cancer. Estimated new cases and deaths from this disease condition in the US in 2012 alone are 241,740 and 28,170, respectively. Current treatment options for patients include surgery, radiation therapy, hormone therapy, chemotherapy, and immune therapy. Unfortunately, these are associated with considerable complications and/or severe side effects.

Dr. Supriya Bavadekar, PhD, RPh, Assistant Professor of Pharmacology at LIU's Arnold & Marie Schwartz College of Pharmacy and Health Sciences, is currently testing carvacrol, a constituent of oregano, on prostate cancer cells. The results of her study demonstrate that the compound induces apoptosis in these cells. Apoptosis, Dr. Bavadekar explains, is programmed cell death, or simply "cell suicide." Dr. Bavadekar and her group are presently trying to determine the signaling pathways that the compound employs to bring about cancer cell suicide.

"We know that oregano possesses anti-bacterial as well as anti-inflammatory properties, but its effects on cancer cells really elevate the spice to the level of a super-spice like turmeric," said Dr. Bavadekar. Though the study is at its preliminary stage, she believes that the initial data indicates a huge potential in terms of carvacrol's use as an anti-cancer agent. "A significant advantage is that oregano is commonly used in food and has a 'Generally Recognized As Safe' status in the US. We expect this to translate into a decreased risk of severe toxic effects."

"Some researchers have previously shown that eating pizza may cut down cancer risk. This effect has been mostly attributed to lycopene, a substance found in tomato sauce, but we now feel that even the oregano seasoning may play a role," stated Dr. Bavadekar. "If the study continues to yield positive results, this super-spice may represent a very promising therapy for patients with prostate cancer."

Tuesday, April 17, 2012

Kidney cancer patients do better when whole kidney is not removed

Surgery to remove only the tumor preferable to removing entire kidney

Kidney cancer patients who had only their tumor removed had better survival than patients who had their entire kidney removed, according to a new study from researchers at the University of Michigan Comprehensive Cancer Center.

After an average of five years, 25 percent of patients who had a so-called partial nephrectomy, in which only the tumor and a small margin of healthy tissue is removed, had died, while 42 percent of patients who had radical nephrectomy, in which the entire kidney is removed, had died, the study found. Results appear in the April 18 Journal of the American Medical Association.

"For patients who are candidates for partial nephrectomy, it should be the preferred treatment option. We found that patients who were younger or had pre-existing medical conditions benefited most from partial nephrectomy," said lead study author Hung-Jui Tan, M.D., a urology resident at the U-M Medical School.

The researchers looked at 7,138 Medicare beneficiaries with early stage kidney cancer up to eight years after treatment. Patients were equally likely to die of kidney cancer, regardless of the type of surgery they received, suggesting that each procedure was equally likely to cure the cancer. The survival discrepancy was found in the number of patients who died from any cause.

The study showed that if only seven patients chose partial nephrectomy over radical nephrectomy, it would save one extra life.

Early stage kidney cancers have become more common recently. These are often discovered by chance when patients receive an X-ray or CT scan for something unrelated.

"As more and more people are identified with these small, early stage cancers, there's more interest in understanding how best to treat these patients," says senior study author David C. Miller, M.D., M.P.H., assistant professor of urology at the U-M Medical School and member of U-M's Institute for Health Care Policy and Innovation.

The question, though, is whether partial nephrectomy – which is a more technically challenging procedure and potentially associated with more short-term complications – is preferable to radical nephrectomy. Removing a kidney can increase the risk of chronic kidney disease, which is associated with lipid disorders, cardiovascular disease and renal failure.

The debate is similar to breast cancer surgery, in which studies have found that lumpectomy plus radiation is comparable to mastectomy. While that choice often comes down to a cosmetic trade-off, the trade-off with kidney cancer is a potential higher risk of short-term complications with partial nephrectomy vs. avoiding chronic kidney disease in the long term.

"This study does not suggest every patient with early stage kidney cancer should get a partial nephrectomy. It supports the notion that we need to expand the use of partial nephrectomy and make it a preferred treatment choice for patients with small tumors as much as possible, to optimize long term survival," Miller says.

Intensity Modulated Radiation Therapy optimal for localized prostate cancer

A treatment for localized prostate cancer known as Intensity Modulated Radiation Therapy (IMRT) is better than conventional conformal radiation therapy (CRT) for reducing certain side effects and preventing cancer recurrence, according to a study published in the April 18, 2012 issue of the Journal of the American Medical Association. In 2012, approximately 241,740 American men will be diagnosed with prostate cancer.

The study also showed IMRT to be as effective as proton therapy, a newer technique that has grown in popularity in recent years.

Ronald Chen, MD, MPH, senior author, says, "Patients and doctors are often drawn to new treatments, but there have not been many studies that directly compare new radiation therapy options to older ones."

Chen is assistant professor of radiation oncology and a research fellow at the Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill. He is a member of UNC Lineberger Comprehensive Cancer Center.

He explains, "In the past 10 years, IMRT has largely replaced conventional CRT as the main radiation technique for prostate cancer, without much data to support it. This study validated our change in practice, showing that IMRT better controls prostate cancer and results in fewer side effects.

"Our data show that in comparing IMRT to proton therapy, IMRT patients had a lower rate of gastrointestinal side effects, but there were no significant differences in rates of other side effects or additional therapies."

Study scientists report that compared to CRT, IMRT was associated with fewer diagnoses of gastrointestinal (GI) symptoms, such as rectal bleeding or diarrhea, hip fractures and additional cancer therapy, but more difficulty with sexual function. Proton therapy was associated with more GI problems than IMRT.

The UNC team used Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2000-2009 for approximately 13,000 patients with non-metastatic prostate cancer. SEER is composed of 16 population-based cancer registries representing approximately 26 percent of the US population.

This study is an example of comparative effectiveness research, which seeks to inform health care decisions by providing new research-based evidence about the benefits and harms of different health care interventions.

Tim Carey, MD, director of the Sheps Center at UNC, said, "This type of research is critical, comparing one type of treatment with alternatives, so that patients and their providers can arrive at the best decisions for each individual."

CRT, IMRT and Proton therapy represent three types of radiation, each attempting to deliver radiation treatment to a tumor while minimizing radiation dose to surrounding organs. Use of proton therapy use in prostate cancer is controversial because of its high cost and unproven benefit compared to other standard forms of radiation like IMRT.

Adverse effects among different radiation therapies for prostate cancer

In an analysis of three different types of radiation therapy used to treat localized prostate cancer, compared with conformal radiation therapy, intensity-modulated radiation therapy (IMRT) was associated with fewer diagnoses of gastrointestinal adverse effects, hip fractures, and receipt of additional cancer treatments but more erectile dysfunction, while proton therapy was associated with more gastrointestinal adverse effects than IMRT, according to a study in the April 18 issue of JAMA, a theme issue on comparative effectiveness research.

Ronald C. Chen, M.D., M.P.H., of the University of North Carolina at Chapel Hill, presented the findings of the study at a JAMA media briefing at the National Press Club.

"Prostate cancer is the most common malignancy in men, with more than 200,000 diagnoses and 30,000 deaths per year. Recent advances in technology have led to costlier treatments such as minimally invasive radical prostatectomy, intensity-modulated radiation therapy, and proton therapy. The adoption of these technologies resulted in a $350 million increase in health care expenditures in 2005 alone," according to background information in the article. Various organizations have called for comparative effectiveness research of localized prostate cancer treatments. "The clinical benefit from these newer treatments is unproven, and comparative effectiveness research examining different radiation techniques is lacking," the authors write.

Dr. Chen and colleagues conducted a study to examine the comparative adverse effects and disease control outcomes after different radiation techniques in a recent cohort of prostate cancer patients. Specifically, the researchers compared IMRT, which has been rapidly adopted and is currently the most commonly used technique, with the older conformal radiation therapy; and compared proton therapy, the use of which also has increased, with IMRT. The population-based study used Surveillance, Epidemiology, and End Results-Medicare-linked data from 2000 through 2009 for patients with localized prostate cancer. The primary outcomes measured were rates of gastrointestinal adverse effects (such as rectal bleeding or diarrhea) and urinary adverse effects, erectile dysfunction, hip fractures, and receipt of additional cancer therapy – as an indicator for disease recurrence.

The use of IMRT vs. conformal radiation therapy increased from 0.15 percent in 2000 to 95.9 percent in 2008. In the propensity-score adjusted analysis (n = 12,976), the researchers found that men treated with IMRT were less likely to receive a diagnosis of gastrointestinal adverse effects and hip fracture but more likely to receive a diagnosis of erectile dysfunction. Also, IMRT patients were nearly 20 percent less likely to receive additional cancer therapy.

In a propensity score-matched comparison between IMRT and proton therapy (n = 1,368), IMRT patients had a 34 percent lower risk of gastrointestinal adverse effects. There were no significant differences in rates of other adverse effects or additional therapies between IMRT and proton therapy.

"Proton therapy is a high-profile, high-cost prostate cancer treatment. Since 2007, multiple proton facilities have been built, and direct-to-consumer advertising is likely to lead to a substantial increase in use," the authors write. "Overall, our results do not clearly demonstrate a clinical benefit to support the recent increase in proton therapy use for prostate cancer."

The researchers add that the findings that patients receiving IMRT were less likely than those receiving conformal radiation therapy to undergo additional cancer treatments is consistent with the use of IMRT to deliver dose-escalated treatment, resulting in improved cancer control, as demonstrated by randomized trials. "Taken together, these results suggest that IMRT facilitated radiation dose escalation without compromising acceptable long-term morbidity."

"Comparative effectiveness research in localized prostate cancer treatments is needed because of the large number of men with this disease and the continued trend of a rapid increase in use of newer and costlier treatments with unproven clinical benefit," the authors write.