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SCCA Network News, Issue 16 Fall 2012

In this issue:

  • Understanding PSA Screening— Pros and Cons for Patients
  • Phase I/II Study for Renal Cell Carcinoma
  • Proton Therapy: Available to Patients in March 2013
  • New SCCA/UWMC Colorectal Cancer Providers
    Bozeman Deaconess Cancer Center
  • Kenneth J. May, Jr., MD, PhD
  • Group Health
  • Amanda Sun, MD, PhD
  • Celebrating a Decade with Olympic Medical Center

Understanding PSA Screening— Pros and Cons for Patients

By Ruth B. Etzioni, PhD
The U.S. Preventive Services Task Force recently recommended against routine prostate-specific antigen (PSA) screening for prostate cancer. The recommendation was based on evidence from two large screening trials conducted in the United States and Europe. The task force concluded that the benefits of PSA screening were likely to be very modest and that there was moderate certainty that they did not outweigh the harms.

What are the harms and benefits of PSA screening? Can these be adequately estimated from screening trials? These are questions that the statistical modeling group within Dr. Ruth B. Etzioni’s lab at Fred Hutchinson Cancer Research Center have been grappling with for at least 10 years.

Since PSA screening has been around in the population for more than 20 years, we have had an opportunity to learn from the population experience about its impacts — both positive and negative. Combining what we have learned from trials and population studies yields a far more nuanced picture than that provided by the task force. We would argue that the evidence is consistent with a significant long-term benefit of PSA screening and that we need to screen — and treat — smarter to reduce harms while preserving benefit.

History and results

The PSA test was introduced in the late 1980s for monitoring existing prostate tumors but became rapidly adopted for screening purposes. Since the early 1990s, prostate cancer deaths have dropped by 44 percent among men over 50, and by almost half among men aged 50 to 74. It is tempting to attribute the drop to changes in screening, but changes in treatment have also occurred. Radical prostatectomy rates increased through the 1980s and into the 1990s. Radiation therapy has evolved enormously, and hormonal therapies are now routinely being used as part of a primary treatment regimen for localized cases. We have concluded that screening and primary treatment changes together plausibly explain about two-thirds of the drop in prostate cancer deaths in this country. Screening alone, without treatment changes, explains one-third, accounting for about 10,000 lives saved in 2010.

At first glance, the task force’s conclusion that the benefits of screening are at most very modest would seem to be at odds with this finding. However, the task force based its conclusion on the absolute numbers of lives saved in the two trials. Although prostate cancer is the most common cancer in men, about three percent of men will actually die from the disease over their lifetimes in the absence of screening. In the trials which had limited follow-up, the number of deaths was considerably lower. In the trial in Europe, only five per 1,000 men enrolled died of prostate cancer in the control group. There was a significant, 20 percent reduction in the risk of dying of prostate cancer in the screened group, but with the low frequency of prostate cancer deaths, this only amounted to about one life saved per 1,000 men screened.

In the U.S. trial, the situation was similar in terms of the low frequency of deaths, but this was compounded by extensive screening in the control group, resulting in no difference in prostate cancer deaths between the two groups (in fact, the number of deaths was slightly higher in the screened group). So the U.S. trial was not able to inform about the benefits of screening versus no screening and the results from Europe almost certainly understated the lives saved over the long term. Taking these results at face value therefore produces an overly negative assessment of screening benefit.

Screening leads to over diagnosing

The relatively short-term results from the trials also produce a skewed assessment of screening harms, particularly over-diagnosis. This is the detection of tumors that would never have been diagnosed without screening. Most of these cases are low risk and can only be harmed by treatment. Prostate cancer treatments can lead to impotence, incontinence, and bowel problems. Different treatments have different side effects and rates of these side effects have been closely studied and are well-understood.

There is no question that any screening benefits that are seen in terms of reduced prostate cancer mortality have come at the cost of over-diagnosis and over-treatment of low-risk tumors, which now form the majority of prostate cancer diagnoses.

However, estimates of over-diagnosis used by the task force — primarily from the European trial — amount to at least 50 percent of screen-detected cases and the corresponding number of cases over diagnosed per life saved is 37. We have estimated that approximately one-fourth of screen-detected cases are over-diagnosed in the U.S. and, over the long term, the number over-diagnosed per life saved is seven. Both of these figures, which are based on U.S. population studies, are dramatically lower than the short-term, trial-based estimates from Europe.

SCCA’s conclusion

In conclusion, we are concerned that a critically important policy decision may have been made by the U.S. Preventive Services Task Force on the basis of an incomplete picture of harms and benefits of PSA screening. We find ourselves in a situation in which we have a beneficial screening test that has likely saved many lives, but it uncovers many more cases that do not need to be treated. The realization that this is the case in contemporary practice has spurred a movement towards active surveillance — intensive monitoring of low-risk tumors — rather than immediate treatment of all newly-diagnosed cancers. We believe that we can also improve the harm/benefit profile of prostate screening by being more selective in referral to biopsy, particularly among older men who are at highest risk of over-diagnosis. The future of prostate screening will rest on our ability to successfully implement screening and treatment policies that are less invasive and less costly than our current practices which are undoubtedly causing a great deal of harm even while reducing prostate cancer morbidity and mortality.

Ruth B. Etzioni, PhD; Member, Public Health Sciences Division, Fred Hutchinson Cancer Research Center.

Dr. Etzioni is involved in the development and implementation of statistical methods for prostate cancer studies at the Hutchinson Center. She currently leads the biostatistics core for the Northwest Prostate Cancer Specialized Program of Research Excellence (SPORE) and is an active member of three national guidelines panels on early detection of prostate cancer.

Phase I/II Study for Renal Cell Carcinoma

Shailender Bhatia, MD, medical oncologist in the Genitourinary Program at Seattle Cancer Care Alliance (SCCA), directs Network participation in Hoosier Oncology Group Protocol GU09-145 (study name: Phase I/II Study of BNC105P in Combination with Everolimus or Following Everolimus for Progressive Metastatic Clear Cell Renal Cell Carcinoma Following Prior Tyrosine Kinase Inhibitors) which is sponsored by Bionomics Limited.

Renal tumors recover from the hypoxic stress caused by the vascular disruption effect of BNC105 through the dysregulated PI3K-mTOR-HIF-VEGF pathway. There is evidence that concurrent blockades of mTOR signaling by pairing Everolimus with BNC105 reduces the ability of renal tumors to recover from BNC105-induced hypoxic stress. Bionomics Limited designed this Phase I/II study to evaluate the combination of Everolimus given by mouth at 10 mg daily and the vascular disrupting agent, BNC105.

The study enrolls patients with metastatic or locally advanced unresectable renal cell carcinoma. Histologic or cytologic proof that the tumor contains a component (any percent) of clear cell renal cell carcinoma and no component of collecting duct or medullary histology is required. Up to 30 percent sarcomatoid histology is permitted.

To be eligible, patients must have progressive disease after receiving one or two prior VEGF-directed tyrosine kinase inhibitors and have measurable disease with no active brain metastases. Prior radiation or bevacizumab and other cancer treatment must have been completed at least 30 days or 14 days, respectively, prior to registration.

During the Phase I portion of the study there were no protocol-defined dose-limiting toxicities observed and no drug-to-drug interactions were demonstrated by plasma PK analysis.

The Phase II dose of BNC105 was determined to be 16 mg/m2 by 10-minute IV infusion on Days 1 and 8 of each 21-day cycle. During Phase II, 134 patients will be randomized 1:1 into Arm A or Arm B.

The primary objective of the Phase II portion of this trial is the improvement in the six-month progression-free survival (PFS) period with the addition of BNC105 to Everolimus. The study is powered to detect improvement from 36 to 60 percent in six-month PFS. Secondary objectives are to determine the response rate of the combination compared to Everolimus alone, determine the PFS with BNC105 alone in patients who progress on Everolimus, evaluate the toxicity of the combination, and determine the overall survival for protocol therapy.

SCCA Network members participating are: Bozeman Deaconess Cancer Center, Cascade Cancer Center, Columbia Basin Hematology and Oncology, Group Health Cooperative, MultiCare Health System, and Olympic Medical Center. SCCA Network staff are actively screening for patients at each institution that has provided access to its electronic medical record system and patient list. Bionomics Limited and Hoosier Oncology Group are willing to add additional performance sites. Contact us at (888) 201-0060 if you have patients for us to screen or if you would like to be added as a performance site.

More information and patient enrollment criteria is on the SCCA website at www.seattlecca.org/clinical-trials/kidneycancer-NCT01034631.cfm.

Proton Therapy: Available to Patients in March 2013

Proton technology has been around since the 1950s and proton therapy, an advanced form of radiation therapy, has been FDA-approved to treat cancer since 1988. In 2009, SCCA formed a joint venture with ProCure Treatment Centers, Inc. (ProCure) breaking ground in 2011 on the campus of Northwest Hospital & Medical Center to build SCCA Proton Therapy, a ProCure Center. In March 2013, less than two years after breaking ground, this new center will treat its first patients.

The first treatment room will host an inclined beam configuration, which is a ProCure and Ion Beam Applications S.A.(IBA) innovation. The inclined beam uses about half the space of a gantry room and is a hybrid of the gantry and fixed beam, and can be used horizontally and at 60 degrees inclined from horizontal to treat most cancers. All of the treatment rooms in the new center will include a robotic Patient Positioning System (PPS) (a ProCure and IBA innovation in collaboration with Forte Automation Systems, Inc.). The PPS has six axes of rotation to provide more exact positioning options. A second treatment room will feature a gantry that can rotate 360 degrees and treat all cancers, opening in July 2013. By the end of 2013, all the treatment rooms will be open and accepting patients.

For more information on treatment services at the SCCA Proton Therapy Center, contact (888) 897-7628 or visit www.procure.com/sea.

New SCCA/UWMC Colorectal Cancer Providers

Gabriela Chiorean, MD

Gabriela Chiorean, MD, joins the faculty at the University of Washington School of Medicine in September as an associate professor of medicine, and the care team at SCCA as an expert in colorectal, gastrointestinal, hepatobiliary, and pancreatic cancers.

Her research is focused on novel therapeutics and biomarker discovery. She conducts Phase I clinical studies, searching for the best treatments for hard-to-treat diseases. For the last 10 years, she has been involved in many clinical and translational research projects, most collaborative and multi-disciplinary. “I believe that a team effort, and sharing ideas and knowledge, leads to the most fulfilling results and forms the most creative environment for novel discoveries,” she says.

Looking toward the future, Chiorean hopes to see the development of easy and intelligent tests that will predict what the best treatments for patients will be, and how to make those with incurable cancers live longer lives.

Alessandro Fichera, MD

Alessandro Fichera, MD, a nationally renowned, board certified colorectal surgeon specializing in the latest surgical techniques and research, joined University of Washington Medicine in July to lead and further develop the colorectal surgery and surgical oncology programs. He spent the last 10 years at the University of Chicago Medical Center where he started and then directed the Colon and Rectal Surgery Residency Training Program.

Trained at the Catholic University of Rome in Italy, Fichera received his doctorate degree with academic honors. He completed his internship and residency in general surgery at the 2nd University of Rome and at the University of Chicago, followed by fellowship training in colorectal surgery at Mt. Sinai in New York.

In addition to his surgical expertise in all types of colorectal disorders, Fichera has a strong interest in inflammatory bowel disease (IBD) and pelvic floor disorders. His research interests focus on IBD, minimally invasive and robotic surgery, prevention, and treatment of colorectal cancers, and the management of a wide variety of digestive diseases. He joins the SCCA/UW Medicine team as a professor of surgery and the new director of UWMC Colorectal Surgery. His long-term goals include the development of multidisciplinary programs for IBD, rectal cancer, and pelvic floor disorders.

Bozeman Deaconess Cancer Center

Bozeman Deaconess Cancer Center (BDCC) continues to offer patients the very latest in cancer care. Because it is an SCCA Network member, BDCC was recently invited by the National Comprehensive Cancer Network® (NCCN) to join NCCN’s Affiliate Research Project. BDCC can now offer as many as 50 new clinical research trials in addition to the trials already available to their patients.

This distinguished selection follows last year’s invitation to participate in the Association of Community Cancer Centers (ACCC) study seeking better ways to measure the quality of care in the community setting for those in late stages of prostate cancer. BDCC business operations manager Spencer Green is serving on the ACCC project’s advisory council.

Finally, BDCC concluded strategic planning for a new linear accelerator and completed its research process for choosing a latest-generation model with on-board imaging. Construction of a vault to house the new machine is slated to begin this fall.

Understanding that treating cancer is not just about providing medical treatment, BDCC provides patients with the assistance of a social worker, financial case manager, and breast care specialists to guide patients through their treatment.

Most recently, Bozeman Deaconess Health Services added clinical patient navigator Kendall Child, FNP. Child is a liaison between patients and specialists when a cancer diagnosis is being determined.

All in all, BDCC continues to improve its cancer treatment services, which means better overall care for patients across southwest Montana.

For more information, visit www.bozemandeaconess.org.

Kenneth J. May, Jr., MD, PhD

Bozeman Deaconess Cancer Center is pleased to welcome Kenneth May, Jr., MD, PhD, to the hematology/oncology team. May recently completed a clinical fellowship in hematology/oncology at the Dana-Farber Cancer Institute/Partners Cancer Care Fellowship Program of Harvard Medical School, and began seeing patients at Bozeman Deaconess in August.

“I am very impressed with the excellent clinicians and staff, as well as the high quality of patient resources at the Cancer Center,” says May, whose primary interests are in prostate cancer and immunotherapies. Through the SCCA Network, he now has experts on both coasts with whom he can consult to provide the best treatments to patients in southwestern Montana.

May earned doctorates of medicine and philosophy in pathology (immunology) from Ohio State University College of Medicine and completed his residency in internal medicine at Brigham and Women’s Hospital (Harvard Medical School). He is recipient of a 2010-2011 Prostate Cancer Foundation Young Investigator Award and a 2011-2012 American Society of Clinical Oncology Conquer Cancer Foundation Young Investigator Award. May is board certified in internal medicine and medical oncology.

Group Health

When it comes to cancer care, Group Health offers patients a broad mix of expertise well beyond oncology services.

More than 1,000 clinicians with Group Health Physicians work together to achieve the best patient outcomes through a culture of collaboration, not competition.

When a primary care doctor suspects cancer, the patient can be easily seen by another specialist. Primary care doctors stay current on the patient’s care via electronic medical records and physical proximity to other specialists. Specialists also provide quick virtual consults since all doctors can see the same test results instantly.

A prime example of this collaborative process involves Michelle Benoit, MD, their newest gynecological oncologist. She provides radical pelvic and oncological surgery for complex gynecologic procedures and gynecologic cancers. She works closely with her colleagues in oncology, primary care, and women’s health, and relies on collaborative adjuvant treatment with Group Health’s medical and radiation oncologists. All of their doctors can easily discuss treatment recommendations and monitor outcomes via frequent communication, electronic medical records, and tumor board meetings.

The integrated Group Health system benefits from Benoit’s expertise, and it also allows her to serve more patients by focusing on her subspecialty skills.

For more information, visit www.ghc.org.

Amanda Sun, MD, PhD

Amanda Sun, MD, PhD, appreciates working in “one of the most dynamic fields in medicine.” It allows her to have close ties to her patients and her research.

Sun trained in internal medicine at Yale University and received her specialty training in hematology/oncology at Brown Medical School. She holds a PhD in molecular biology from Dartmouth Medical School and is board certified in hematology and medical oncology. She has a special interest in epidemiology, obesity, and breast cancer.

“As an oncologist, I like to be the consultant and advocate for my patients to come up with the best treatment plan,” she says. “I’m fully supportive of all alternatives available as part of treatment, including clinical studies.”

Sun believes SCCA Network membership builds on the foundation of care that Group Health patients already receive. For example, when a patient with underlying diabetes has chemotherapy or receives steroids, Sun can communicate with the personal physician to make sure all the patient’s health needs are being addressed.

“Group Health has a tremendous advantage by having among the most advanced electronic medical records,” she says.

Celebrating a Decade with Olympic Medical Center

SCCA Network membership began for Olympic Medical Center (OMC) in 2002 as a means of bringing world-class cancer services and leading-edge therapies through clinical trials to residents of the North Olympic Peninsula. SCCA chose OMC as its first community based cancer care provider for their professional staff and services at the time. Expanding over the years, in 2007, OMC unveiled the new Primo Construction Medical Oncology wing, bringing medical oncology under the same roof as the Littlejohn Family Radiation Oncology wing.

“SCCA’s mission is to make sure cancer patients in communities across the North Olympic Peninsula have access to the best treatments and technologies available,” says Cecilia Zapata, director of Regional and Global Network, and Physician Educational Outreach at SCCA.

Looking forward to 2013, OMC continues its collaborative efforts with pilot sites at MultiCare and Skagit Valley Hospital to develop new metrics as part of SCCA Network’s Site Quality Metric/Clinical Performance project.

OMC & SCCA commemorated this anniversary by hosting a picnic. “We’re excited to celebrate our 10-year partnership with our very first affiliate member – Olympic Medical Center,” Zapata says, “and we look forward to the next 10 years of continued collaboration.”

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