Kosj Yamoah, M.D., Ph.D.

A new study published in January in the journal BMC Cancer, led by Kosj Yamoah, M.D., Ph.D., a resident in the Department of Radiation Oncology at Thomas Jefferson University and Hospital, takes aim at the issue by investigating prostate cancer diagnoses and treatment delivery in black men living in the West African region, in order to devise research strategies to help improve health outcomes.

Overall, many men are diagnosed at a later stage, with more than half opting out of treatment, they found. The researchers point to stigmas about cancer as a root of the problem.

“Cancer could eclipse infectious diseases as an epidemic if more awareness and intervention doesn’t come about,” said Dr. Yamoah, who grew up in Ghana until age 20, when he came to the United States. “Cancer can be very hush-hush because of cultural and financial issues and social stigmas associated with the disease. We need to bring awareness and address the needs of the population and barriers to care.”

“Cancer is still perceived as a death sentence,” he added. “People are scared to go to their doctor to find out if they have it, let alone to follow through with treatment.”

In a retrospective analysis of 379 patients referred for treatment at the National Center for Radiotherapy and Nuclear Medicine at the Korle Bu Teaching Hospital (KBTH) from 2003 to 2009, the team found that 33 percent were diagnosed with metastatic disease and 70 percent had a prostate-specific antigen (PSA) score four times higher than men in the United States or Europe at time of diagnosis.

PSA screening rates in Ghana are low, the authors explain, and many men opt out of radiation therapy and other therapies after diagnosis. Out of the 251 patients eligible for radiation therapy, only 141 patients actually received external beam radiation therapy.

Among patients with at least two years of follow up after external beam radiation therapy, three- and five-year PSA-failure free survival was 73.8 percent and 65.1 percent respectively. In the U.S., those percentages are 90 percent and 85 percent, respectively.

Reasons recognized by KBTH clinicians for patients declining radiation therapy included: the prohibitive cost of treatment, fear of radiation, and a state of denial based on their perception of disease originating solely from spiritual causes rather than biologic processes.

The data, which to date provides the largest source of published information on outcomes for prostate cancer treatment in the West African region, is a call to action, according to the authors.

The research team plans to develop treatment regimens tailored to the needs of Ghanaian men, which may differ from guidelines currently utilized in the Unites States and Europe in order to better address the disease burden and improve mortality rates in Ghana. That could mean more frequent PSA screening.

“There is controversy in the United States with PSA testing, but in a country like Ghana, there may be a role for PSA screening, even infrequent screening, because of all the late stage cancers we are finding,” said Dr. Yamoah.

The team has established collaboration between two institutions with the hope of improving prostate cancer treatment and plan to start more clinical trials to develop novel, shorter course treatments for locally-advanced prostate cancer.

“Based on these results, our group has proposed a plan for future research aimed at identifying an appropriate role for PSA screening in this population, developing radiation therapy treatment schedules that better fulfill the needs of Ghanaian prostate cancer patients, and contributing to understanding genetic factors associated with prostate cancer risk and treatment response,” the authors write.

Sarah E. Hegarty, a statistical analyst in the Department Pharmacology & Experimental Therapeutics at Jefferson, and Terry Hyslop, Ph.D., also of the Department Pharmacology & Experimental Therapeutics at Jefferson, were also part of the study.

Richard Pestell, M.D., Ph.D.

Researchers at the Kimmel Cancer Center at Jefferson (KCC) have developed potentially game-changing diagnostic and prognostic genetic tests shown to better predict prostate cancer survival outcomes and distinguish clinically-relevant cancers.

The team, led by Richard G. Pestell, M.D., Ph.D., Director of the KCC and the Chair of the Department of Cancer Biology at Thomas Jefferson University, report their preclinical findings from a blinded, retrospective analysis of over 350 patients and mouse study in a recent issue of the journal of Cancer Research.

Using an oncogene-specific prostate cancer molecular signature, the researchers were able to separate out men who died of prostate cancer versus those who lived, and more specifically, identifying men who died on average after 30 months (recurrence free survival). The diagnostic test distinguished patients with clinically relevant prostate cancer from normal prostate in men with elevated prostate-specific antigen (PSA) levels.

The researchers worked with three oncogenes previously associated with poorer outcomes in prostate cancer: c-Myc , Ha-Ras, and v-Src.

The test, the researchers say, is superior to several previously published gene tests and to the Gleason scale, which is a rating given to prostate cancer based upon its microscopic appearance and currently used to help evaluate the prognosis of men with the disease.

Given the diversity of prostate cancer outcomes—some men live two years after diagnosis, others live for more than 20 more years— a new oncogene-specific signature like this could not only help better identify prostate cancer risk but also test targeted therapies—by way of a new prostate cancer cell line.

These studies describe the first isogenic prostate cancer cell lines that metastasize reliably in immune competent mice. Previous studies were in immune deficient mice.

“This oncogene signature shows further value over current biomarkers of prediction and outcomes,” said Dr. Pestell. “Such a signature and cell line may also enable the identification of targets for therapies to better treat prostate cancer, which takes the lives of over 27,000 men a year.”

In breast cancer, the identification of tumor subsets with various gene signatures has improved clinical care for patients because of targeted therapies.

The work here by the KCC aims to identify gene patterns and subsequent tests in prostate cancer that could serve similar purposes. But to help develop such therapies, model systems that closely resemble human disease are required. To date, there have been several limitations with currently available cell lines.

Although important transplantation experiments have been conducted using human prostate cancer cell lines in immune deficient animals, the immune system plays an important role in prostate cancer onset and progression making it imperative to develop prostate cancer cell lines that can be studied in immune competent animals.

Also, although the transgenic mouse has been an effective model to study the molecular basis of human cancers, the prostate cancer mouse models have long latency and often unpredictable metastasis.

Here, the researchers succeeded in overcoming these issues.

The oncogene-specific prostate cancer molecular signatures were recapitulated in human prostate cancer and validated in distinct populations of patients as a prognostic and diagnostic test.

What’s more, the researchers demonstrated how the isogenic prostate cancer cell lines metastasized in immune-competent mice.

“Identification of gene signatures in breast cancer has allowed for a deeper understanding of the disease, and this paper moves us steps closer to being able to follow a similar trajectory with prostate cancer. Today, such an understanding and a formidable testing ground for new therapies is lacking for this disease,” Dr. Pestell said. “With this new oncogene-specific prostate cancer molecular signature, we have a valuable prognostic and diagnostic resource that could help change the way we manage and treat prostate cancer.”

Other researchers in the study include Xiaoming Ju, Adam Ertel, Mathew Casimiro, Zuoren Yu, Hui Meng, Peter A. McCue, Rhonda Walters, and Paolo Fortina.

Karen Knudsen, Ph.D.

Elevated levels of Cyclin D1b could function as a novel biomarker of lethal metastatic disease in prostate cancer patients, according to a pre-clinical study published ahead of print on December 21 in the Journal of Clinical Investigation by researchers at the Kimmel Cancer Center at Jefferson.

The group, headed by Karen E. Knudsen, Ph.D., Professor and Hilary Koprowski Chair, Departments of Cancer Biology, Urology, and Radiation Oncology at Thomas Jefferson University and Deputy Director for Basic Science at the KCC, found that Cyclin D1b, a variant of the cell cycle regulator Cyclin D1a, functions independently of the cell cycle to promote metastasis in both early and late stage prostate cancer.

Rather, Cyclin D1b, but not Cyclin D1a, regulates a large gene network, the researchers found, which was shown to cooperate with androgen receptor (AR) signaling to fuel metastatic progression in multiple models of prostate cancer.

Studies have shown that Cyclin D1b expression is elevated in early stages of prostate cancer (in up to 30% of primary disease), and researchers have now demonstrated that this occurs more frequently in late stage castration-resistant prostate cancer: up to 80%.

Cyclin D1b expression is also highly correlated with that of the pro-metastatic gene SNAI2 (Slug), which the group identified as regulated by cooperative signaling between Cyclin D1b and AR.

“Numerous clinical and pre-clinical studies have effectively demonstrated that AR signaling is critical for progression to metastatic disease, but our knowledge of AR targets which can induce metastatic phenotypes is limited,” said Dr. Knudsen. “Our data describe how cross talk between the cell cycle and AR can rewire the AR signaling axis to enhance the expression of genes which elicit metastasis in both early and castration resistant prostate cancer models.”

“We found that Cyclin D1b can directly promote AR dependent expression of the gene SNAI2 (Slug), which dramatically increased metastatic events to soft tissues in animal models,” she added.

Metastatic castration resistant prostate cancer represents the most lethal form of the disease, which arises when AR is reactivated despite continued hormone therapy.

Soft tissue metastasis to the liver and lung represents a particularly aggressive form of prostate cancer, whose presence predicts for decreased survival time in prostate cancer patients.

Currently, there is little knowledge as to how these metastatic events occur, and identification of pathways and biomarkers of this lethal event could greatly benefit prostate cancer patients.

Using various in vitro and in vivo models, researchers found that Slug enhances the ability of cells to colonize soft tissues, which resulted in a higher incidence of metastasis in the liver and lung.

Given the inability to manage AR signaling in metastatic castration resistant prostate cancer, Slug driven pathways could be leveraged to dramatically limit the incidence of soft tissue metastasis and improve patient morbidity and mortality, researchers believe.

“Identification of AR driven pathways which mediate metastatic progression represents a significant leap forward in our attempts to effectively manage prostate cancer progression,” said Dr. Knudsen. “Cyclin D1b and Slug can likely be used as biomarkers to identify patients with an increased risk of metastasis, and will eventually provide us with novel “druggable” targets downstream of AR and Slug which can be exploited to dramatically reduce the incidence of these lethal metastatic tumors.”

This study was completed as a result of an inter-institutional team effort, including the contributions of the lead author and graduate student Michael A. Augello of the Department of Cancer Biology at Thomas Jefferson University, as well as key collaborators: Dr. Felix Feng (University of Michigan), Dr. Alessandro Fatatis (Drexel University), Dr. Tapio Visakorpi (University of Tampere), Dr. Donald McDonnell (Duke University), Dr. C. Burd (University of Ohio), Dr. D E. Frigo (University of Houston) and Dr. Ruth Birbe of Thomas Jefferson University.

Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology, Medical Oncology and Urology at Jefferson Medical College of Thomas Jefferson University and Jefferson’s Kimmel Cancer Center

Men who had high levels of the activated Stat5 protein in their prostate cancer after a radical prostatectomy were more likely to have a recurrence or die from the disease compared to men who had little to no presence of the growth protein, according to a recent study published in Human Pathology by Jefferson’s Kimmel Cancer Center researchers.

This suggests, Stat5, a protein that when activated signals cancer cells to grow and survive, could be an ideal biomarker to help guide patients and physicians for future treatment.

The research team, led by Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology, Medical Oncology and Urology at Jefferson Medical College of Thomas Jefferson University and Jefferson’s Kimmel Cancer Center, examined prostate cancer biopsies and tumor tissues obtained from 562 men who underwent a radical prostatectomy, comparing Stat5 levels with outcome.

They also looked at prostate tumor tissue in 106 patients who were under a “watchful waiting” or active surveillance treatment plan and had no neoadjuvant therapy. Samples were taken at the time of diagnosis.

“In both cohorts, if the patient had increased Stat5 in their prostate cancer, that patient was more likely to experience prostate recurrence or die from his disease compared to patients who had very low levels of Stat5,” said Dr. Nevalainen.

More specifically, patients without detectable nuclear Stat5a/b expression had recurrence-free survival of 72 percent at eight years. In contrast, patients with high nuclear Stat5a/b score had a recurrence-free survival rate of 42 percent at eight years. This indicates an approximately 30 percent benefit in recurrence-free survival at eight years associated with negative status for nuclear Stat5a/b expression in prostate cancer.

For those on active surveillance, patients with low nuclear Stat5a/b scores had a lower probability of prostate cancer specific death. There was an approximate 50 percent benefit in prostate cancer specific survival at 10 years associated with a negative status for Stat5.

The findings support a series of past and ongoing studies investigating Stat5 and its predictive capabilities led by Dr. Nevalainen.

A study from 2005, published in the journal Clinical Cancer Research, showed similar findings to this current study. Activated Stat5 in prostate cancer predicted outcome; however, there were differences in the cohorts. The key limitation of the previous study was the heterogeneous cohort of the patients, who received different adjuvant therapies at the time / after radical prostatectomy.  In the present study, the patients received a single mode of surgical intervention with no neoadjuvant therapies.

In 2008, in a another study published in Clinical Cancer Research, researchers showed that they can effectively kill prostate cancer cells in both the laboratory and in experimental animal models by blocking Stat5. That provided a proof of principle that Stat5 is a therapeutic target protein for prostate cancer.

Next, the group will be investigating Stat5’s predictive response after radiation therapy.

“There is an urgent need for reliable biomarkers to identify prostate cancer patients whose cancer is most likely to recur after the initial therapy and progress to advanced disease,” said Dr. Nevalainen. “The data presented here supports the initiation of prospective studies to determine the clinical utility of Stat5 as a prognostic and predictive marker in prostate cancer.”

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number R01CA113580.

Several media outlets covered the study, including Urology Times and Prostate Cancer Foundation news section. Links to those article are below.

“Protein predicts post-RP cancer recurrence, death”

“Stat5 Predicts Early Disease Recurrence and Prostate Cancer Specific Deaths in Patients After Radical Prostatectomy”

The release was picked up by  Science Daily, Medical News Today, and Yahoo! News.

A newly discovered function of PARP-1 could be the key to more effective therapeutics to treat advanced prostate cancer patients, a recent preclinical study published in Cancer Discovery by Jefferson’s Kimmel Cancer Center researchers suggests.

Karen E. Knudsen, Ph.D., Professor in the Departments of Cancer Biology, Urology, & Radiation Oncology

The team, led by Karen E. Knudsen, Ph.D., Professor in the Departments of Cancer Biology, Urology, & Radiation Oncology at Thomas Jefferson University, found that functions of PARP-1 not only include DNA damage repair but also androgen receptor (AR) regulation in advanced prostate cancer growth and progression.  PARP inhibition in various models was found to suppress AR activity, which fuels prostate growth.

Researchers believe that the dual functions of PARP-1—as both a regulator of AR as well as critical for DNA damage repair—could be leveraged for therapeutic benefit.  PARP inhibitors could slow down advanced-stage prostate cancer and shrink tumors, the team surmises.

“We hope to capitalize on this previously unknown function in PARP-1 in prostate cancer,” said Dr. Knudsen. “Our data show that PARP-1 plays a major role in controlling AR function and that, when suppressed with inhibitors, enhanced anti-tumor effects of castration and delayed onset to castration resistance. “

“This is the basis to support a clinical trial investigating PARP-1 inhibitors in patients with advanced disease,” she added.

Today, PARP-1 is seen as a valuable target because of its involvement in DNA damage repair for cancer cells. The therapy has been successful when combined with DNA-damaging drugs because it heightens the apoptotic activity of these drugs. In other words, it helps halt tumor growth by stopping DNA repair in various cancers.

Prostate cancer is dependent on AR activity for growth and survival, and is largely resistant to standard chemotherapy. AR-directed therapies are the first-line intervention for patients with advanced disease; however, recurrent tumors arise when AR is reactivated, a common occurrence in the castrate-resistant stage of the disease.

Therefore, there is a dire need to develop means to suppress the AR function in these patients. With this new role defined, PARP inhibitors targeting both functions could sensitize prostate cancer cells to DNA damage, and potentially improve the efficacy of AR-directed therapies in these patients, the researchers suggest in the paper.

Almost 40 percent of men with prostate cancer progress into an advanced stage, termed castrate-resistant prostate cancer, where chemotherapy and other therapies have little to no effect.

Using various in vitro and in vivo model systems, the researchers found that PARP-1 activity is required for AR function and is increased in castrate-resistant prostate cancer.  Additionally, inhibiting PARP-1 suppressed proliferation of cultured, primary human tumor specimens in a state-of-the-art system.

“These findings introduce a paradigm shift with regard to PARP-1 in prostate cancer,” said Dr. Knudsen, “and provide the basis for new therapies that could help a whole population of cancer patients who have little options.”

Dr. Knudsen recently received a two-year Challenge Award worth $1 million from the Prostate Cancer Foundation (PCF) for her work with PARP-1 and prostate cancer, and attended PCF’s 10^th annual fundraiser in Philadelphia.

The study from Dr. Knudsen’s laboratory was a result of an inter-institutional team effort, including the contributions of lead author and postdoctoral fellow Dr. Matthew Schiewer, of the Department of Cancer Biology at Thomas Jefferson University, as well as key collaborators: Dr. Felix Feng (University of Michigan), Drs. Wayne Tilley and Lisa Butler (University of Adelaide), Dr. Ganesh Raj (UT Southwestern), Dr. Peter McCue, Dr. Leonard Gomella, Dr. Adam Dicker, Dr. Jonathan Brody, and Dr. John Pascal of Thomas Jefferson University.

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This work was supported by NIH grants (R01 CA099996-09, and R01 ES016675-11), the Commonwealth of Pennsylvania grant, a Prostate Cancer Foundation Creativity award, a Prostate Cancer Foundation Young Investigator Award grants from the National Health and Medical Research Council of Australia, a Cancer Council of South Australia Senior Research Fellowship, and Pre-doctoral Fellowships from the DOD.

Eagles player Jason Avant and Dr. Leonard Gomella, Chair of Urology at Jefferson

September is Prostate Cancer Awareness month, and Thomas Jefferson University Hospitals has again teamed up with the Philadelphia Eagles to educate fans and others about prostate health and to raise cancer awareness.

To help kick off the campaign, Jefferson will serve as the presenting partner at the Sunday, September 16 game versus the Baltimore Ravens, with Edouard Trabulsi, M.D., Director of Multidisciplinary Genitourinary Oncology Center of the Kimmel Cancer Center at Jefferson (KCC),  and David P. McQuaid, FACHE, President, Thomas Jefferson University Hospitals, Inc., receiving Eagles jerseys on the field before kickoff.

“The KCC and our Departments of Urology, Medical Oncology and Radiation Oncology are deeply honored and grateful to once again have the Eagles as our partners,” said Leonard Gomella, MD, chair of the Department of Urology at Thomas Jefferson University Hospitals and director of clinical affairs at the KCC. “Prostate cancer is the second leading cause of cancer death among men, and over 200,000 will be diagnosed this year alone.  That’s why it’s so important for men to take their prostate health seriously.”

Prostate cancer is the most common type of cancer among men, with one in six men being diagnosed in his lifetime, and most treatable if caught early.

“In the months ahead, Jefferson and the Eagles look forward to more victories on the field and in raising prostate cancer awareness,” Dr. Gomella said.

Eagles wide receiver Jason Avant is also joining forces with Jefferson to help spread prostate health awareness, participating in several community events and a public service announcement with Dr. Gomella on the importance of prostate health and screening.

For the 23^rd consecutive year, Jefferson Hospitals will also offer free prostate health and cancer screenings on September 19 and 25 from 9 a.m. to 3 p.m. (registration required). Call 1-800-JEFF-NOW to make an appointment.

Karen Knudsen, Ph.D.

A group of investigators led by Dr. Karen Knudsen was awarded a 2-year challenge grant of one million dollars by the Prostate Cancer Foundation.  The details of this award (from the PCF web site) are:

2012 Movember-PCF Challenge Award

Lead Investigator:
Karen Knudsen, PhD
Thomas Jefferson University

Title
Interrogation of Aberrant DNA Repair in Sporadic Prostate Cancer

Co-investigators: Johann De Bono, MD, PhD, Royal Marsden Hospital; Felix Feng, MD, University of Michigan; Mark Rubin, MD, Weill Cornell Medical College.

What this means to patients: Understanding the extent and impact of alterations in DNA Damage Response pathways in prostate cancer patients will target specific DNA repair problems and allow effective Precision Medicine (tailored treatment regimens) based on molecular subtyping of patient DDR alterations matched to drug therapy.

Synopsis: DNA Damage Response (DDR) pathway alterations are changes in DNA repair mechanisms that promote genomic instability and have been associated with local and advanced prostate cancer. Dr. Knudsen and team will identify and comprehensively determine the frequency of abiraterone in DDR pathways at different stages of prostate cancer progression. They will determine the clinical relevance of these DNA repair defects in prostate cancer patients and their role in the development and progression of treatment-resistant prostate cancer. Previous studies showed that the DNA repair protein PARP1 is elevated in tumors of advanced prostate cancer patients. PARP1 is recruited to sites of androgen receptor function and is required for AR activity in both hormone-dependent and treatment refractory disease. PARP inhibition therefore has dual effects on cancerous cells; 1) impairs DNA repair in tumors and, 2) suppresses AR signaling—halting cancer progression. Dr. Knudsen and colleagues will evaluate effects of combination therapy with PARP inhibitors and next generation anti-androgens in treatment-resistant prostate cancer patients.

Liver metastases predicts shorter overall survival in men with metastatic castration-refractory prostate cancer (mCRPC), according to data being presented at the 2012 American Society of Clinical Oncology Annual Meeting in Chicago. (Abstract # 4655, Sunday, June 3, 8:00 AM – 12:00 PM CST, S Hall A2).

In a phase III trial, lead study author William Kevin Kelly, DO, Thomas Jefferson University Hospital and the Kimmel Cancer Center at Jefferson, and colleagues from the Alliance for Clinical Trials in Oncology, found that men without liver metastases lived 8.2 months longer compared to men whose cancer did metastasize, despite both groups having similar progression free survival and response to docetaxel based chemotherapy.

The multi-institutional study included 1,050 patients from the CALGB 90401 trial, a randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with mCRPC.

For the investigation, researchers assessed the prognostic significance of liver metastases in predicting overall survival and progression free survival, adjusting for stratification factors.

Fifty-nine (5.6%) of those patients had documented liver metastases.  Patients with liver metastases had higher baseline alkaline phosphatase (ALK) and lactate dehydrogenase (ADH) levels compared to patients without liver metastases. The median overall survival time in patients with liver metastases was 14.4 compared to 22.6 months for patients without liver metastasis(hazard ratio (HR) 1.4) . The HR for treatment effect (docetaxel and prednisone with either bevacizumab or placebo) for liver metastases was not statistically significant for either group.

The full abstract can be found here. http://abstract.asco.org/AbstView_114_96038.html

This article was adapted from an OncLive story posted on May 21, 2012.

Leonard G. Gomella, M.D, chair of the Department of Urology at Thomas Jefferson University Hospital and director of Clinical Affairs, Jefferson’s Kimmel Cancer Center, was part of the team to present new findings from the IMPACT trial looking at the immunotherapy sipuleucel-T (Provenge) in men with advanced prostate cancer.

The abstract was presented at the American Urological Association (AUA) Annual Meeting in Atlanta.

Results from the exploratory, multi-institutional analysis provides important insight into how the cross-over design of the IMPACT trial may have affected the overall survival findings, and supports a greater treatment effect of sipuleucel-T than previously reported.

In the study,  researchers administered the vaccine APC8015F to a group of patients from the control arm of three randomized, Phase 3 clinical trials evaluating sipuleucel-T, a similar, FDA-approved cancer vaccine for metastatic castrate resistant prostate cancer.

APC8015F is made from immune system cells taken from a patient with prostate cancer; however, unlike sipuleucel-T, which is never frozen, APC8015F is cryopreserved at a time before the disease progressed.

Of the 249 men in the control arm, 155 received APC8015F. Those receiving APC8015F demonstrated similar benefits to those receiving sipuleucel-T. However, these patients were grouped with the placebo arm, when the benefits were calculated.

Removing the patients that received APC8015F and comparing just the patients that received placebo alone to those receiving sipuleucel-T alone more than doubles the 4.1-month median survival benefit found in the IMPACT trial.

“From my viewpoint, the benefit of sipuleucel-T has been understated because many of the patients who received the frozen product on the control actually enjoyed a longer survival, decreasing the difference between the control arm and the treatment arm,” Dr. Gomella tells OncLive.

“In fact, if you look at our analysis of the patients who received the frozen product on the control arm and those that did not receive it, there was a significant survival advantage to those patients who did receive the frozen product. So it actually made a difference between the control arm and treatment arm much closer. And if you actually take those patients out who did not receive the frozen product on the control arm, that survival difference actually approaches 10 to 11 months.”

Watch the full interview here: http://www.onclive.com/onclive-tv/Dr-Gomella-on-the-IMPACT-Trial-Survival-Benefit

Source: OncLive

Mathew Thakur, PhD, professor of Radiology at Jefferson Medical College of Thomas Jefferson University and the Director of the Laboratories of Radiopharmaceutical Research and Molecular Imaging

Jefferson’s Kimmel Cancer Center and the Department of Radiology at Thomas Jefferson University received a five-year, $2.6 million grant from the National Institutes of Health (NIH) to investigate a potentially revolutionary method that can stage prostate cancers and detect recurrent disease so accurately, it would significantly reduce the number of confirmation biopsies. Such biopsies can be invasive, costly, and often lead to false-positive readings.

The new technique involves the use of a positron emission tomography (PET) scan and a novel imaging agent.

The study is being led by Mathew Thakur, PhD, professor of Radiology at Jefferson Medical College of Thomas Jefferson University and the Director of the Laboratories of Radiopharmaceutical Research and Molecular Imaging.

Prostate specific antigen (PSA) measurements, ultrasonography and magnetic resonance imaging (MRI) remain standard tools for diagnosis and management of prostate cancer; however, each requires an invasive biopsy for histologic confirmation.

Biopsies are associated with morbidity and high costs, and more than 65 percent of the 1.5 million biopsies performed each year in the U.S. show benign pathology, indicating a high false-positive rate for these standard diagnostic tools.

These limitations, the researchers say, demonstrate a dire need for noninvasive methods that can accurately stage prostate cancer, detect recurrent disease and image metastatic lesions with improved reliability.

Dr. Thakur and colleagues are studying Cu-64 peptide biomolecules to evaluate prostate cancer tumors via PET imaging. These agents detect prostate cancer by finding a biomarker called VPAC1, which is overexpressed as the tumor develops.

“The challenge has been to develop an imaging agent that will target a specific, fingerprint biomarker that visualizes prostate cancer early and reliably,” said Dr. Thakur, who is also a member of Jefferson’s Kimmel Cancer Center.

Previous studies with Cu-64 peptides from Dr. Thakur yielded promising results in stratifying breast cancer.  A preclinical study published in the Journal of Nuclear Medicine in late 2009 found that ⁶⁴Cu-TP3805 detected tumors overexpressing the VPAC1 oncogene more accurately in mice than ¹⁸F-FDG, a commonly used agent for imaging tumors.

With this NIH grant, the researchers will test the hypothesis in both mice and humans.  They will evaluate two Cu-64 peptides specific for VPAC1 in mice and perform a feasibility study in 25 pre-operative prostate cancer patients, using the best suited Cu-64 peptide determined from the mouse studies.

“This noninvasive method could significantly contribute to the management of prostate cancer,” said Dr. Thakur. “It would result in a reduction of unnecessary biopsy procedures and under treatment or over treatment that yield minimal benefits, incontinence, or impotence.”

Other researchers include Ethan Halpern, MD, Charles Intenzo, MD, and Sung Kim, MD of the Department of Radiology, Edouard Trabulsi, MD of the Department of Urology and Eric Wickstrom, PhD, of the Department of Biochemistry and Molecular Biology. The team will partner with NuView, a molecular imaging technology firm, on the study.

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This study was funded by NIH’s National Cancer Institute (Grant No. 1R01CA157372-01A)

Dr. Leonard Gomella, Program Director of 2012's IPCC

Leonard G. Gomella, M.D., FACS, Chair of Urology at Thomas Jefferson University Hospital and Director of Clinical Affairs at the Kimmel Cancer Center at Jefferson, will serve as the Program Director for the Fifth Annual Interdisciplinary Prostate Cancer Congress (IPCC) at the New York Marriott East Side in New York City on March 31.

This full-day continuing medical education (CME) activity entitled Novel Perspectives – Evolving Therapies and Advances In Standard of Care will address the differences that currently exist between urologists’, medical oncologists’, and radiation oncologists’ approaches to treating prostate cancer.

World-renowned thought leaders have been brought together to foster consensus about the best management of prostate cancer from the vantage point of interdisciplinary care teams. Topics of vital interest that will be include: hormonal therapies; imaging and staging; surgical advances; radiation therapies; and emerging multimodal therapies.

The IPCC will include interactive cases designed to highlight multidisciplinary approaches for the management of prostate cancer with the overall goal of improving patient outcomes.

Topics include  prostate-specific antigen testing in diagnosing patients with prostate cancer, and emerging bone-related therapies for treating prostate cancer.

Dr. Gomella told OncLive that the value of the conference for attendees is its focus on practical applications of these new developments. “When they go back to the patient setting, they can actually use [this information] in their daily patient care,” he said.

For more information, please visit, http://cancerlearning.onclive.com/index.cfm/fuseaction/conference.showOverview/id/5/conference_id/702/index.php

http://www.onclive.com/publications/Oncology-live/2012/january-2012/IPCC-Conference-to-Focus-on-Issues-Facing-Clinicians

Heather Montie, Ph.D., a post-doctoral research fellow in the Department of Biochemistry and Molecular Biology, has received a Prostate Cancer Foundation Young Investigator Award for her work with androgen receptor (AR) acetylation and its role in castration-resistant prostate cancer.

Young Investigator awards are designed to promote long-term careers in the field of prostate cancer by providing three year grants for transformational research focused on prostate cancer treatments to improve patient outcomes. Since 2007, PCF has invested more than $20 million in Young Investigator grants.

“PCF-supported young investigators have changed the scope of prostate cancer research, advancing treatment sciences and improving the lives of patients worldwide,” said Howard Soule, PhD, chief science officer and executive vice president of PCF. “It is with great pride and appreciation that PCF can now announce our young investigator program spans across six countries and 42 research institutes.”

Prostate cancer is driven by the male hormones, androgens which mediate their activity through the androgen receptor. Unfortunately most prostate cancerous tumors progressively become resistant to the preferred treatment modality, androgen deprivation therapy. One of the mechanisms proposed to enhance the activity of androgen receptors in castration-resistant prostate cancer, even in the absence of androgens, is the addition of a small chemical group/moiety to the AR protein. This modification of AR is termed ‘acetylation’ and is proposed to convert the protein to a ‘super AR.’

However, there is currently no experimental data to show that AR acetylation directly enhances AR-dependent prostate cancer cell viability.

Dr. Montie proposes to evaluate the role of AR acetylation in the enhanced AR functional activity central to CRPC. She will study the precise mechanisms by which this modification of AR enhances its cancer-promoting activity. Dr. Montie will also validate the potential of AR acetylation as a therapeutic target for castrate-resistant prostate cancer.

A total of 15 competitive research grants have been awarded to-date in 2012, bringing the total of young investigators awarded to 89.

Each Young Investigator recipient is awarded $225,000 over a three-year period.

Dr. Montie received the 2012 John A. Moran PCF Young Investigator Award. 

Visit here for more on the Young Investigator awards.

Karen Knudsen, PhD, a Professor of Cancer Biology, Urology and Radiation Oncology

Curcumin, an active component of the Indian curry spice turmeric, may help slow down tumor growth in castration-resistant prostate cancer patients on androgen deprivation therapy (ADT), a study from researchers at Jefferson’s Kimmel Cancer Center suggests.

Reporting in a recent issue of Cancer Research, Karen Knudsen, Ph.D., a Professor of Cancer Biology, Urology and Radiation Oncology at Thomas Jefferson University, Supriya Shah, a Jefferson graduate student in Cancer Biology, and colleagues observed in a pre-clinical study that curcumin suppresses two known nuclear receptor activators, p300 and CBP (or CREB1-binding protein), which have been shown to work against ADT.

ADT aims to inhibit the androgen receptor—an important male hormone in the development and progression of prostate cancer—in patients. But a major mechanism of therapeutic failure and progression to advanced disease is inappropriate reactivation of this receptor. Sophisticated tumor cells, with the help of p300 and CBP, sometimes bypass the therapy.

Thus, development of novel targets that act in concert with the therapy would be of benefit to patients with castration-resistant prostate cancer.

For the study, prostate cancer cells were subjected to hormone deprivation in the presence and absence of curcumin with “physiologically attainable’ doses. (Previous studies, which found similar results, included doses that were not realistic.)

Curcumin augments the results of ADT, and reduced cell number compared to ADT alone, the researchers found. Moreover, the spice was found to be a potent inhibitor of both cell cycle and survival in prostate cancer cells.

To help support their findings, the researchers also investigated curcumin in mice, which were castrated to mimic ADT. They were randomized into two cohorts: curcumin and control. Tumor growth and mass were significantly reduced in the mice with curcumin, the researchers report.

These data demonstrate for the first time that curcumin not only hampers the transition of ADT-sensitive disease to castration-resistance, but is also effective in blocking the growth of established castrate-resistant prostate tumors.

“This study sets the stage for further development of curcumin as a novel agent to target androgen receptor signaling,” said Dr. Knudsen. “It also has implications beyond prostate cancer since p300 and CBP are important in other malignancies, like breast cancer. In tumors where these play an important function, curcumin may prove to be a promising therapeutic agent.”

On Tuesday, November, 17th 2011, the Kimmel Cancer Center at Jefferson held the Third Annual Men’s Event benefiting prostate cancer research and patient care at the Prime Rib Restaurant in Philadelphia. The Men’s Event was emceed by Philadelphia Eagles Longsnapper, motivational speaker and magician, Jon Dorenbos.

Receiving the Symbol of Courage was John Beuhler, prostate cancer survivor and grateful patient of Thomas Jefferson University Hospital.  The Symbol of Caring was presented to Kenneth Boone, board member of Thomas Jefferson University Hospital.

Special guests included Amber-Joi Watkins, Miss USA Pennsylvania and Julianna White, Miss USA New Jersey. Guests enjoyed a dinner, silent and live auction, and casino.

The Lead Sponsor was Bill Frankel of Frankel Enterprises. Kimmel Cancer Center would also like to thank the following sponsors:

The Third Annual Men’s Event would not have been possible without the tremendous work and support of our Committee members:

Special thanks to Gerard Tomko Wedding Photography for donating his services in-kind.

Xinglei Shen, M.D., a resident in Jefferson’s Department of Radiation Oncology and a part-time master’s degree student in the Jefferson School of Population Health

Brachytherapy for high-risk prostate cancers patients has historically been considered a less effective modality, but a new study from radiation oncologists at the Kimmel Cancer Center at Jefferson suggests otherwise. A population-based analysis looking at almost 13,000 cases revealed that men who received brachytherapy alone or in combination with external beam radiation therapy (EBRT) had significantly reduced mortality rates.

Their findings are reported online January 23 in the International Journal of Radiation Oncology,Biology,Physics.

Brachytherapy involves the precise placement of radiation sources directly at the site of a tumor and is typically used to treat low and intermediate risk prostate cancers. However, brachytherapy treatment for high-risk patients is less common and controversial, given in part to early retrospective studies that found it to be associated with lower cure rates compared to EBRT.

Many experts believe that these early series were limited by poor brachytherapy technique, and that high-quality contemporary brachytherapy may be an effective tool against high-risk prostate cancer.

“The study contradicts traditional policies of using brachytherapy in just low and intermediate risk patients by suggesting there may instead be an improvement in prostate cancer survival for high-risk patients,” said co-author Timothy Showalter, M.D., assistant professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital, and associate research member of Jefferson’s Kimmel Cancer Center. “Although studies like this cannot prove an advantage for brachytherapy, our report does suggest that brachytherapy is no less effective than EBRT and should be considered for some men with high-risk prostate cancer.”

Researchers identified 12,745 Surveillance, Epidemiology and End Results database patients diagnosed from 1988 to 2002 with high-grade prostate cancer of poorly differentiated grade and treated with brachytherapy (7.1 percent), EBRT alone (73.5 percent) or brachytherapy plus EBRT (19.1 percent). The team used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on prostate cancer-specific mortality.

Treatment with brachytherapy alone or brachytherapy in combination with EBRT, the researchers found, was associated with significant reduction in prostate cancer-specific mortality rates compared to EBRT alone.

Significant predictors of use of brachytherapy or brachytherapy plus EBRT were younger age, later year of diagnosis, urban residence and earlier T-stage.

According to the researchers, including lead author Xinglei Shen, M.D., a resident in Jefferson’s Department of Radiation Oncology and a part-time master’s degree student in the Jefferson School of Population Health, the study’s findings provide ample evidence to further study brachytherapy as part of an effective treatment strategy for men with high-grade prostate cancer.

“Today, for the most part, brachytherapy is not being used for these high-risk patients or even recommended,” Dr. Shen said. “But if you look at the biology and theory behind it, it makes sense: you can really give a lot more dose with brachytherapy than with EBRT alone to the prostate. And this presents an opportunity for high-risk patients.”

Jefferson’s Kimmel Cancer Center has started a Phase I clinical trial investigating the latest prostate cancer chemotherapy drug to extend survival, Cabazitaxel, in combination with radiation and hormone therapy. This first-of-its-kind multimodality approach could improve disease control and eventually survival for locally advanced prostate cancer patients.

The single-center, open-label, non-randomized Phase I study of weekly Cabazitaxel with concurrent intensity modulated radiation therapy (IMRT) and androgen deprivation therapy will test its safety and the tolerable maximum dosing.

Cabazitaxel was approved in the U.S. for second-line use in advanced hormone-refractory prostate cancer in men in 2010, and has been described as a major advance in chemotherapy for advanced prostate cancer. It extended overall survival by 2.4 months when compared with mitoxantrone in patients who were previously treated with docetaxel. However, a multimodality approach with the drug has never been studied.

“We know the drug is effective in prostate cancer, but there is no study with radiation and hormone therapy yet,” said principal investigator Jianqing Lin, M.D., an assistant professor of medical oncology at Thomas Jefferson University Hospital. “Concurrent radiation may have a better control for localized disease, and better long-term survival for these high-risk patients.”

IMRT is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor; androgen deprivation therapy is a treatment to suppress or block the production or action of male hormones. Enrolled men will receive weekly treatments of the chemotherapy drug and hormone therapy and then every three months until two years after completion of IMRT.

For the clinical trial, Dr. Lin is partnering with co-investigator Timothy Showalter, M.D., an assistant professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital.

For further information, please contact the Kimmel Cancer Center at Jefferson’s Clinical Research Management Office at 215-955-1661.

Ulrich Rodeck, M.D., Ph.D.

Ulrich Rodeck, M.D., Ph.D., a professor in the Department of Dermatology and Cutaneous Biology, at Jefferson Medical College, Thomas Jefferson University, received the Ben Franklin-Prostate Cancer Foundation Creativity award for his work in improving the therapeutic window of radiation therapy for prostate cancer.

Radiation therapy of locally advanced prostate cancer is associated with severe toxicity limits. Dr. Rodeck will test the hypothesis that modulators of inflammation will preferentially protect normal tissues, but not tumor tissues against radiation-associated toxicity. A series of novel radioprotective compounds have been selected to test this hypothesis in models of prostate cancer and in patients.

This radiobiology proposal will allow higher doses of external beam radiation to be administered, resulting in improved cancer control with reduced side effects to normal adjacent tissue.

Dr. Rodeck received the award on October 4 during the Prostate Cancer Foundation award ceremony and auction at the Union League.

Philadelphia Magazine also featured photos from the Prostate Cancer Foundation event on October 11.

October 2011 marks 20 years of exceptional cancer care and research at KCC

From October forward, the Kimmel Cancer Center at Jefferson (KCC), a National Cancer Institute-designated cancer center, is celebrating 20 years of service to the community and the groundbreaking cancer research from the scientists and physicians who’ve provided an invaluable contribution to medical science and healthcare.

“This is truly a milestone for the Kimmel Cancer Center—it’s two decades of caring and collaborating to beat cancer,” says Richard Pestell, M.D., Ph.D., director of the KCC and Chair of the Department of Cancer Biology at Thomas Jefferson University.

“With our multidisciplinary approach, KCC’s team of clinicians and researchers has continued to put their best feet forward to provide excellent, stand-out personalized care for cancer patients in the Philadelphia region and beyond and uncover new pathways to better prevent, diagnose and treat the disease,” he added.

Today, the KCC offers up an experienced team of medical and radiation oncologists, surgeons, pathologists, urologists, neurosurgeons, nurses and other specialists for patients as they fight against cancer. With the Jefferson Breast Care Center, the Bodine Center for Radiation Therapy, the Myrna Brind Center of Integrative Medicine, and Jefferson Pancreatic, Biliary Tract and Related Cancer Center, to name a few, patients have access to the best facilities, providers and technologies for cancer screening and treatment.

It was October 1991 when the Jefferson Cancer Institute opened, with the dedication of the Bluemle Life Science Building on the Thomas Jefferson University campus. Four years later, with the awarding of a Cancer Center Support Grant, the National Institutes of Health National Cancer Institute (NCI) officially recognized it as one of only 54 NCI-designated cancer centers in the U.S. at the time. The institute took its current name in 1996 when businessman and philanthropist Sidney Kimmel made a generous donation to the institute to expand its research activities.

The donation to Jefferson is not a “gift,” but “an investment for humanity,” Mr. Kimmel told the Philadelphia Inquirer in 1996. “I really believe we’re going to have a breakthrough” in cancer research.

Living up to his expectations, KCC cancer researchers have made significant contributions over the last two decades, including better care in prostate cancer (Leonard Gomella, M.D.); new targets and diagnostics for prostate and breast cancer (Hallgeir Rui, M.D., Ph.D., Dr. Pestell); discoveries in colon cancer (Scott Waldman, M.D., Ph.D); pioneering discoveries in cancer metabolism and stem cells (Michael Lisanti, M.D. Ph.D., Dr. Pestell); better bone marrow transplants (Neal Flomenberg, M.D.); more selective radiation treatment (Adam Dicker, M.D.); and new areas of the human genome to treat (Isidore Rigoutsos, Ph.D., and  Paolo M. Fortina, M.D., Ph.D.).

Dr. Pestell, who became director in 2005, has made significant contributions to understanding cell cycle regulation and the aberrations that can lead to cells turning cancerous. His work identified new molecular markers, and new targets for cancer treatment. An internationally renowned expert in oncology and endocrinology, Dr. Pestell’s record of research funding is outstanding, securing substantial National Institutes of Health grants for the KCC.

Today, KCC’s well-funded basic science programs include cell biology, immunology and structural biology, developmental therapeutics, melanoma, leukemia/lymphoma, prostate and breast cancers, and gastrointestinal and genitourinary cancers. KCC also conducts numerous cancer clinical trials each year aimed at prevention and treatment of cancer.

Two recent clinical trials have resulted in the addition of new procedures at Thomas Jefferson University Hospital.  For example, in the Department of Urology, under chairman Leonard Gomella, M.D, a bladder cancer diagnostic tool using an imaging agent and blue light technology is now helping physicians better detect tumors along the bladder lining. Also, a new, two-step approach to half-match bone marrow transplants (where a patient can use a sibling or parent as a donor) developed by Chair of Medical Oncology Neal Flomenberg, M.D., is proving to be a success for blood cancer patients whose options were otherwise limited.  Jefferson is the only hospital in the region performing half-match procedures.

Since being appointed as chair of the Department of Radiation Oncology in 2010, Adam Dicker, M.D., Ph.D., has led extensive clinic renovations and the ongoing addition of new technologies. That includes Bodine’s recently acquired radiation therapy equipment for head and neck and prostate cancer patients and an upcoming radiosurgey instrument designed to deliver higher doses of radiation to smaller areas. Bodine’s state-of-the-art brachytherapy suite is also set to open in early 2012.

Last year, Charles J. Yeo, M.D., Chair of Surgery, performed his 1,000^th Whipple procedure.  The Whipple procedure is a major surgical operation involving removal of portions of the pancreas, bile duct and duodenum, and is typically performed to treat malignant tumors involving the pancreas, common bile duct or duodenum.  Jefferson’s surgery department treats more pancreatic cases than anywhere in the region.

Thomas Jefferson University Hospital is consistently ranked in the top 50 best hospitals for treating cancer in America (#31 in 2011) in U.S. News and World Report. What’s more, the hospital has moved up more than 20 places in the past five years for cancer.

Robert M. Den, M.D., Department of Radiation Oncology

Radiation oncologist Robert B. Den, M.D., recently joined Thomas Jefferson University Hospital as an attending physician, and was also named an assistant professor at Jefferson Medical College of Thomas Jefferson University in the Department of Radiation Oncology.

Dr. Den is a clinical scientist who specializes in the treatment of prostate cancer, combining his laboratory research that investigates novel anticancer agents in combination with radiation and hormonal therapy for locally advanced and high risk prostate cancer.

A graduate of Yale University with a B.S. in chemistry, Dr. Den received his medical degree from Harvard University in 2006. Dr. Den’s postgraduate training began at Massachusetts General Hospital in Boston as an intern of medicine before becoming a resident in radiation oncology at Thomas Jefferson University Hospital from 2007 to 2010, and ultimately serving as chief resident (2010-2011).

Dr. Den will serve as a radiation oncologist in the Bodine Center for Radiation Therapy at the Kimmel Cancer Center at Jefferson.

“I’m looking forward to continuing my prostate cancer research with my colleagues here at Jefferson, including the department’s chair, Dr. Adam Dicker, and Dr. Karen Knudsen,” said Dr. Den. “What’s equally important is taking that research to bedside so patients may benefit.”

“Our goal is to personalize the care for each man with prostate cancer, to effectively eradicate the disease,” he added.

Dr. Den is the 2010 recipient of the prestigious Prostate Cancer Foundation Ben Franklin Young Investigator Award. That work is examining the importance of the retinoblastoma tumor suppressor gene, RB, in the response of prostate cancer cells to radiation and hormonal therapy. The research begins to address the ability to personalize therapy based on RB status.

Expanding on that research, Dr. Den is also the principal investigator for a Department of Defense Physician Research Training Award to study whether RB can be used to determine which therapeutic modalities should be administered to patients with locally advanced prostate cancer.  He is also working towards opening a clinical trial to study preoperative radiation for high risk prostate cancer patients.

Dr. Den is member of several professional societies including the American Society for Therapeutic Radiology and Oncology and the American Society of Clinical Oncology, and has co-authored over 25 scientific papers, abstracts and book chapters.

Timothy Showalter, MD, Department of Radiation Oncology

Receiving radiation therapy immediately after a radical prostatectomy is a cost-effective treatment for prostate cancer patients when compared with waiting and acting on elevated prostate-specific antigen (PSA) levels, according to a new study by researchers at Thomas Jefferson University and Hospital.

What’s more, a separate, but related study, found that urologists were less likely than radiation oncologists to recommend adjuvant radiation therapy or to believe it improves overall survival.

There has been question over whether administering adjuvant radiation therapy after removing the prostate is an appropriate course of action because of associated toxicities, risk of overtreatment and costs, even with data supporting its benefits to overall survival, but a new decision analysis published online in the Annals of Oncology on June 9 found that the procedure is a practical option for patients.

“This work demonstrates that adjuvant radiation therapy is a cost-effective strategy for selected patients after prostatectomy,” said Laura Pizzi, PharmD, associate professor at the Jefferson School of Pharmacy, and senior author of the study. “It is typical for cancer treatments to provide clinical be

nefit at a cost; however, the cost per success that we reported for adjuvant radiation therapy is on the low end when one broadly considers the cost per success reported for other cancer treatments.”

The objective of the study was to construct a decision analytic model to estimate the real world cost of adjuvant radiation therapy versus observation from the payers’ perspective, using peer-reviewed, published data from a Southwest Oncology Group prospective, randomized trial. Side effects, overtreatment and the price tag were taken into account.

Nearly one-third of newly diagnosed men with prostate cancer—almost 220,000 men were diagnosed in 2010—undergo radical prostatectomy. Previous studies have shown that adjuvant radiation therapy improves biochemical progression-free survival and overall survival for these patients; however, most do not receive the treatment.

“Despite being shown to be effective, less than 20 percent of qualifying patients receive it,” said Timothy Showalter, M.D., assistant professor of Radiation Oncology at Thomas Jefferson University, associate research member of the Kimmel Cancer Center at Jefferson, and lead author of the study. “Although not all patients will benefit from adjuvant radiation therapy, the level of utilization is low

er than expected based on the positive, published results of randomized clinical trials.”

“Studies like this one are an important step toward establishing the value of this treatment and suggest that adjuvant radiation therapy should have a role in the treatment of selected patients. Our group has embarked on a large-scale research program to evaluate and improve treatments after prostatectomy for patients with high-risk prostate cancer, and these studies are critical foundational accomplishments,” he added.

Side effects, risk of overtreatment (the subset of patients who may not have failed PSA tests after radiation therapy despite adverse pathologic factors) and the high price have cast some doubts for patients and physicians alike. In many cases, physicians choose to observe patients closely with serial PSA tests and offer radiation therapy only as a salvage treatment after a rise in the PSA levels.

But this new analysis, Dr. Showalter says, “substantiates the benefit of adjuvant radiation therapy,” taking these factors into consideration, including toxicity and overtreatment.

Another study by Dr. Showalter and colleagues, published online in the International Journal of Radiation Oncology, Biology and Physics on May 25, attempted to gauge physician beliefs and practices for adjuvant radiation therapy after a radical prostatectomy.

Leonard Gomella, MD, Department of Urology

Significant discordance was identified. An online survey found that urologists were less likely to recommend radiation therapy immediately after a radical prostatectomy than radiation oncologists. Instead, those clinicians most likely opt to perform frequent PSA tests to monitor cancer, recommending salvage therapy if levels become elevated.

The investigators designed a Web-based survey of post-radiation prostatectomy radiation therapy beliefs and policies. A total of 218 radiation oncologists and 92 urologists completed the survey instrument. Adjuvant radiation therapy after a radical prostatectomy was recommended for qualifying patients by 78 percent of radiation oncologists and only 44 percent of urologists.

Urologists were also less likely to believe that adjuvant radiation therapy improves overall survival (71 percent of radiation oncologists vs. 63 percent of urologists), and perceived higher rates of radiation-related toxicities than radiation oncologists. Physicians’ estimates of radiation-induced urinary problems affected their likelihood of recommending radiation therapy.

The fact that adjuvant radiation therapy use has not increased since the publication of randomized trials supporting the therapy suggests that clinicians have not embraced it, according to the researchers.

“These two studies provide important insights into decision-making regarding radiation therapy after prostatectomy,” said Leonard Gomella, M.D., the Bernard W. Godwin, Jr. Professor of Prostate Cancer and Chairman of the Department of Urology at Thomas Jefferson University. “The disagreement between urologists and radiation oncologists highlights the need for additional research to determine the role of adjuvant therapy in selected patients, and is another example of the importance of multidisciplinary prostate cancer care for our patients to make informed medical decisions.”