EMBARGOED FOR RELEASE
Wednesday, February 13, 2008 12:01 AM EST
-- Most Older Men with Early-Stage Prostate Cancer Can Avoid Treatment;
Mortality 60 Percent Lower in Men Receiving Radiation for Recurrent Prostate Cancer;
Sunitinib Associated with Higher Rates of Heart Failure than Previously Recognized;
Partial Kidney Removal Is Under-Utilized in Patients with Small Renal Tumors --
SAN FRANCISCO, Ca. – New research on the treatment of genitourinary cancers is being presented at the first Genitourinary Cancers Symposium, being held February 14-16, 2008, at the San Francisco Marriott. A media presscast highlighting the noteworthy studies summarized below can be accessed at www.asco.org/GUpresskit08.
Highlighted studies include:
- Research concluding that most older men with early-stage prostate cancer will not require treatment or will die of other causes before their cancer progresses significantly.
- An analysis finding that providing radiation therapy to men who have rising prostate-specific antigen (PSA) levels following radical prostatectomy can reduce the risk of dying from prostate cancer by more than 60 percent, with the largest benefit in men with rapidly rising PSA levels.
- A study finding that 15 percent of patients with renal cell carcinoma or gastrointestinal stromal tumor (GIST) who were treated with sunitinib (Sutent) experienced heart failure, a rate higher than previously recognized, signaling the need for routine cardiac monitoring in these patients.
- A study finding that women, older patients and those with cerebrovascular disease with small renal tumors are more likely to undergo complete surgical removal of the kidney (radical nephrectomy) than partial nephrectomy, despite the risk of impaired kidney function with radical nephrectomy, and the equal effectiveness of the two approaches.
“These studies shed light on the optimal way to manage the care of patients with prostate and kidney cancers, and confirm that we can’t take a ‘one-size-fits-all’ approach to treatment,” said Howard M. Sandler, MD, MS, an official with the Genitourinary Cancers Symposium. “As we learn more about the biology of these diseases and how patients respond to different forms of treatment, we’ll be able to tailor therapy appropriately for individual patients.”
Genitourinary cancers include cancers of the prostate, kidney, bladder and testis, as well as less common cancers such as those of the penis, ureters and other urinary organs. Each year nearly 350,000 people in the United States are diagnosed with genitourinary cancers and more than 55,000 die of these diseases. The most common genitourinary cancer is prostate cancer, which is diagnosed in more than 218,000 men and claims more than 27,000 lives each year.
The Genitourinary Cancers Symposium is co-sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Therapeutic Radiology and Oncology (ASTRO) and the Society of Urologic Oncology (SUO).
Oral Abstract Presentation A
Thursday, February 14, 12:30 PM PST |
Lead Author: Grace Lu-Yao, PhD
Cancer Institute of New Jersey
Robert Wood Johnson Medical School
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Most Older Men with Early-Stage Prostate Cancer Can Avoid Treatment
[Note: This summary contains updated data not in the abstract.]
Most older men with early-stage prostate cancer will not require treatment or will die of other causes before their cancer progresses significantly, according to a new study that examined data on more than 9,000 older men with localized prostate cancer who were not treated for the disease. This study is one of the largest to date to observe the course of early-stage prostate cancer in older men.
“Because prostate cancer therapies are associated with significant side effects, our data can help patients make better informed decisions about the most appropriate approach for them and potentially avoid treatment without adversely affecting their health,” said Grace Lu-Yao, PhD, cancer epidemiologist at The Cancer Institute of New Jersey, associate professor at UMDNJ-Robert Wood Johnson Medical School and School of Public Health and the study’s lead author. Dr. Lu-Yao added that men who choose not to undergo treatment should be carefully monitored for rising PSA and other signs of cancer growth.
The management of older men with early-stage prostate cancer has been the subject of some debate. Some studies have suggested that men who receive therapy fare better than those who do not, while other research has reported that many of these men can safely forego therapy and will eventually die with their prostate cancer, but not from it.
This study is one of the first to describe the natural history of prostate cancer that is not immediately treated, during the current era when PSA testing is common. This is important because PSA tests can detect cancer six to 13 years earlier than traditional diagnostic methods, and researchers have found that PSA-diagnosed cancers can often differ in stage and biology.
In this study, the investigators examined data on 9,018 men from the U.S. Surveillance, Epidemiology and End Results (SEER) database who had been diagnosed with stage I or II prostate cancer between 1992 and 2002 and who did not initially receive local therapy (such as surgery or radiation therapy) or hormonal therapy within six months of diagnosis. The median age of the men at diagnosis was 77.
The researchers found that prostate cancers in the study group were generally slow growing. Most of the men did not have any therapy (approximately two out of three died of other causes or did not experience cancer progression that resulted in the use of surgery or radiation therapy). Of the 2,675 men who did have some treatment, the median time between diagnosis and the start of cancer therapy was 10.6 years (127 months).
As expected, men with less aggressive disease (low or moderate grade) fared better than those with high-grade cancers. After 10 years, 3 to 7 percent of those with low or moderate-grade disease had died of prostate cancer, compared with 23 percent of men with high-grade cancers. Dr. Lu-Yao noted that the clinical outcomes of this study population were also substantially more favorable than those observed in previous studies, perhaps because the use of PSA tests has resulted in earlier detection of prostate cancer.
Disease trajectory of untreated localized prostate cancer in elderly men: a population-based study
G. Lu-Yao, M. J. Barry, A. Zietman, M. O'Leary, B. Walker-Corkery, W. Shih, Y. Lin, R. DiPaola, P. Albertsen, S. Yao
Background: Understanding the disease trajectory of untreated prostate cancer is critical for treatment decisions. We evaluated the natural history of men diagnosed with localized prostate cancer who did not receive initial therapy for localized cancer. Methods: Medicare claims data linked to the Surveillance, Epidemiology and End Results (SEER) data were used to assemble the cohort. Men with other cancers were excluded from the study.
Findings: The population-based cohort consisted of 9,018 men diagnosed with T1/T2 prostate cancer in 1992-2002 who did not receive initial local therapy or androgen deprivation within 6 months of cancer diagnosis. Median age at cancer diagnosis was 77 (range 66 to 104) and median follow-up was 94 months. Median time to any cancer therapy (surgery, radiation, chemotherapy or androgen deprivation) was 127 months. During the study period, 6,523 (72%) of the study cohort died of competing causes of death or did not have documented cancer complications that required surgery or radiation. The corresponding statistics for low, moderate and high-grade cancer are 87% (162/187), 73%(5,521/7,544), and 65%(840/1,287), respectively. Ten-year prostate cancer specific mortality was 6%(11/187), 3%(256/7,544), and 17% (215/1,287) for low, moderate and high-grade cancer, respectively.
| |
Outcome |
|
|
|
| Time since cancer diagnosis |
Use of cancer therapy N=9,018 |
Had TURP due to cancer N=7,224*> |
Treatment for spinal cord compression N=9,018 |
Prostate cancer mortality N=9,018 |
| 5 years |
2,391 (26.5%) |
259 (3.6%) |
29 (0.3%) |
344 (3.8%) |
| 10 years |
2,675 (29.7%) |
324 (4.5%) |
44 (0.5%) |
482 (5.3%) |
* Excludes men who had TURP before cancer diagnosis.
Conclusion: The majority of men with T1/T2 prostate cancer died of competing causes of death or did not develop complications that required surgery or radiation therapy. Active surveillance may be a reasonable option for elderly patients with localized prostate cancer, especially among those without high-grade cancer.
Disclosures for Research Team: Nothing to disclose.
General Session I
Saturday, February 16, 8:15 AM PST |
Lead Author: Bruce Trock, MD
Johns Hopkins University School of Medicine
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Analysis Finds Radiation for Recurrent Prostate Cancer Significantly Improves Survival
An analysis of patient data finds for the first time that providing radiation therapy to men with rising prostate-specific antigen (PSA) levels following radical prostatectomy (called salvage radiotherapy or SRT) can reduce the risk of dying from prostate cancer by more than 60 percent, with the greatest benefit seen in men with rapidly rising PSA levels. Moreover, they found that the benefits of SRT appear to persist even when it is given up to two years after PSA levels begin to rise.
"These findings are the first to support the effectiveness of salvage radiotherapy for improving survival in men with recurrent prostate cancer," said lead author Bruce Trock, MD, associate professor of urology, epidemiology, oncology and environmental health sciences at Johns Hopkins University School of Medicine. "If validated, these results suggest that for high-risk prostate cancer, radiotherapy should be given promptly when there is evidence for recurrence after radical prostatectomy, as early salvage radiotherapy may improve overall survival."
The investigators of this study compared prostate cancer-specific survival (the probability of not dying from prostate cancer) among men with rising PSA levels after radical prostatectomy (biochemical recurrence). Of these men, 160 had received SRT alone, 78 received SRT plus hormonal therapy and 397 received no SRT or hormonal therapy. Dr. Trock noted that this study was not a prospective randomized clinical trial, but a retrospective analysis of men who had already been treated.
After 10 years, 86 percent of men in the SRT group and 82 percent of men in the SRT/hormonal therapy group had not died from prostate cancer, versus 62 percent of men who received no salvage therapy. These results did not change after taking into account individual patient characteristics associated with prognosis. The investigators also found that SRT had to be given soon after recurrence – prostate cancer-specific survival improved only when SRT was given less than two years after biochemical recurrence.
The impact of SRT was particularly strong in men whose PSA levels doubled in less than six months (an indicator of more aggressive disease); SRT reduced the risk of prostate cancer death in these men by 86 percent. SRT did not significantly reduce the risk of death among men whose PSA levels doubled in six months or more, due to the fact that these men had less aggressive disease and may have fared well even without radiation therapy.
The researchers cautioned that despite the evidence that SRT appears to improve survival, confirmation is needed in other comparable groups of men, and a randomized clinical trial will ultimately be needed to determine the impact of SRT on survival.
Prostate cancer-specific survival in men with biochemical recurrence after radical prostatectomy: Impact of salvage radiotherapy vs. observation
B. Trock, M. Han, S. J. Freedland, E. B. Humphreys, T. L. DeWeese, A. W. Partin, P. C. Walsh
Background: Biochemical recurrence after radical prostatectomy (RP) often prompts salvage radiotherapy (SRT), but it is unknown whether SRT confers a survival benefit, and if so, the subgroup most likely to benefit. We compared prostate cancer-specific survival (PCSS) in men given SRT vs no therapy after biochemical recurrence following RP.
Methods: Retrospective analysis of a cohort of 635 men undergoing RP from 1982-2004, who experienced biochemical recurrence and received no salvage therapy (n=397), SRT alone (n=160) or SRT plus hormonal therapy (SRT+HT) (n=78). PCSS was defined from biochemical recurrence until death from disease or censoring, and analyzed with Cox time-dependent covariates models.
Results: With median follow-up of 6 years after biochemical recurrence and 9 years after RP, 116 men (18%) died from prostate cancer. SRT alone produced a highly significant 3-fold improvement in PCSS compared to no salvage, hazard ratio [HR]=0.32 (95% confidence interval (CI), 0.19-0.54), p<.0001. The beneficial effect of SRT was limited to men with PSA doubling time (PSADT) < 6 months, HR=0.14 (95% CI 0.05-0.39). In contrast, SRT did not improve PCSS in men with PSADT > 6 months. This effect remained after adjustment for pathologic stage, Gleason score, time from RP to biochemical recurrence, and year of RP. SRT+HT produced similar significant improvement in PCSS. Early salvage treatment was critical; SRT improved PCSS only if given <2 years after biochemical recurrence. Compared to no salvage, SRT begun <2 years after biochemical recurrence again significantly improved PCSS only for men with PSADT<6 months, HR=0.14 (95% CI 0.06-0.34), p<.0001. This subgroup (SRT <2 years after recurrence, PSADT<6) represented 66% of SRT patients and 24% of the total sample. In contrast, SRT begun > 2 years after biochemical recurrence did not improve PCSS regardless of PSADT.
Conclusions: This study shows for the first time that SRT provides an important increase in PCSS for men with biochemical recurrence. Men with PSADT<6 months who received SRT within 2 years of biochemical recurrence exhibited highly significant improvement in PCSS, regardless of other prognostic features.
Disclosures for Research Team: Employment or leadership position with Oncomethylome Sciences and Veridex, LLC; Stock ownership in Oncomethylome Science, Veridex, LLC and Johnson & Johnson.
Poster Session E
Saturday, February 16, 11:30 AM PST |
Lead Author: Melinda Telli, MD
Stanford University School of Medicine
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Sunitinib Is Associated with More Heart Failure than Previously Recognized;
Need for Close Monitoring
[Note: This summary contains updated data not in the abstract.]
A new study shows that 15 percent of patients with renal cell carcinoma or gastrointestinal stromal tumor (GIST) who were treated with sunitinib (Sutent) experienced heart failure, a weakening of the heart muscle that impairs the heart’s ability to pump blood to the rest of the body. Symptoms of heart failure include shortness of breath and fatigue, and increased risk of death.
Sunitinib, a capsule that is taken orally, is a drug approved for the treatment of renal cell carcinoma (an aggressive form of kidney cancer) and a rare type of gastrointestinal cancer called GIST. It works by inhibiting the growth of blood vessels that tumors need to grow and spread to other parts of the body. The drug may also slow the growth and division of cancer cells. Sunitinib is currently being widely tested for the treatment of other cancers, both early- and advanced-stage.
“Our data demonstrate the need for routine cardiac monitoring in patients receiving sunitinib,” said lead author Melinda Telli, MD, a postdoctoral fellow in medical oncology at Stanford University School of Medicine. “Cardiac adverse effects need to be carefully examined in future trials of sunitinib to determine the factors that place patients at risk for this complication. That information will allow us to administer this medication more safely to patients for whom the benefits of treatment clearly outweigh the risks.”
Animal studies have shown that sunitinib can be toxic to cardiac cells and that this effect may be exacerbated by high blood pressure (another side effect of sunitinib). Previous studies have reported that up to 8 percent of patients taking sunitinib experienced heart failure, but patients in those studies were taking the drug as part of participation in a clinical trial. Clinical trials often exclude patients with pre-existing cardiac conditions. The current study is the first to evaluate cardiovascular side effects in patients who were taking sunitinib outside of the context of a clinical trial, making them more representative of the general population of patients currently receiving sunitinib.
In this study, researchers examined the occurrence of symptomatic heart failure among 48 patients who had received sunitinib as treatment for renal cell carcinoma or GIST between July 2004 and July 2007 at the Stanford University Comprehensive Cancer Center. Seven patients (15 percent) experienced symptomatic left ventricular dysfunction or heart failure during sunitinib treatment. These effects were observed as early as 22 days and as late as 435 days after beginning sunitinib therapy, and persisted in three patients despite discontinuation of sunitinib and initiation of heart failure medication. Patients with a history of heart failure, a history of coronary artery disease or a low body mass index were more likely to experience heart failure associated with sunitinib.
Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate
M. L. Telli, R. M. Witteles, G. A. Fisher, S. Srinivas
Background: In the pivotal phase III metastatic renal cell carcinoma trial, updated data indicates that 21% of sunitinib-treated patients experienced a decline in left ventricular ejection fraction to below normal. This cardiac dysfunction was previously reported to be reversible and not associated with clinical sequelae. We conducted a retrospective analysis of our institutional experience of cardiotoxicity with sunitinib after observing a higher than expected incidence of symptomatic heart failure.
Methods: Patients receiving sunitinib at the Stanford University Comprehensive Cancer Center for either renal cell carcinoma or gastrointestinal stromal tumor from July 1, 2004 to July 1, 2007 were identified. Medical records were reviewed and those patients experiencing symptomatic Grade 3/4 left ventricular systolic dysfunction according to the Common Terminology Criteria for Adverse Events, Version 3.0 were identified. The time course of development of cardiotoxicity was evaluated with a focus on the cardiac follow-up among patients diagnosed with cardiotoxicity. Potential cardiac risk factors were analyzed.
Results: Forty-eight patients treated with sunitinib were assessable. Six patients experienced symptomatic Grade 3/4 left ventricular dysfunction during treatment with sunitinib. One additional patient had probable congestive heart failure that was not confirmed by echocardiography. Mean age of patients experiencing cardiotoxicity was 65 years. All patients presented with symptoms of heart failure. This cardiotoxicity was observed 22 - 435 days after initiation of sunitinib. Three out of five patients with follow-up cardiac evaluations had persistent left ventricular dysfunction after discontinuation of sunitinib and initiation of standard heart failure therapy. Additional analyses of cardiac risk factors will be presented.
Conclusions: Among patients treated with sunitinib at our institution, 12.5% developed symptomatic Grade 3/4 heart failure, a rate much higher than previously reported. Future studies of sunitinib-related cardiotoxicity are urgently needed, particularly as the oncologic indications for this drug continue to expand.
Disclosures for Research Team: Honoraria from Pfizer; Research funding from Pfizer.
Poster Session E
Saturday, February 16, 11:30 AM PST |
Lead Author: William Huang, MD
New York University School of Medicine
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Partial Kidney Removal Is Under-Utilized in Patients with Small Renal Tumors
Researchers report that women, older patients and patients with cerebrovascular disease who have small renal tumors are more likely to undergo complete surgical removal of the affected kidney (radical nephrectomy) than partial nephrectomy, despite evidence showing that the two approaches are equally effective, and that partial nephrectomy helps preserve kidney function in cancer patients better than the more aggressive surgery.
“Just as lumpectomy can be less invasive but as effective as mastectomy for treating breast cancer, people with kidney cancer should be aware that partial nephrectomy is not only an option, but may be a better option than radical nephrectomy in many circumstances because it may help preserve kidney function in patients with renal tumors. We need to do a better job of educating both patients and physicians about this topic,” said William Huang, MD, assistant professor of urologic oncology at New York University School of Medicine and the study’s lead author.
The investigators examined Surveillance, Epidemiology and End Results (SEER) data from 1995 through 2002 to identify pre-operative factors that differed between 2,547 patients with small renal tumors who had radical nephrectomy and 556 who had partial nephrectomy. The study was the first to analyze this topic using information from a population-based database, as opposed to data from a single institution.
Investigators found that patients who had partial kidney removal were more likely to be younger, male, married and treated at a later date during the study period, which may mean that the prevalence of partial nephrectomy is slowly increasing. Women, older patients and those with cerebrovascular disease were less likely to have partial nephrectomy. For example, 20.5 percent of men and 22.4 percent of patients ages 66 to 69 had partial nephrectomy, versus 16 percent of women and only 7.1 percent of patients aged 85 and older.
Dr. Huang speculated that surgeons may prefer radical nephrectomy over partial nephrectomy because it is technically less challenging to perform and has a lower risk of complications. For these reasons, surgeons may believe that the procedure is a better option for older patients and those with cerebrovascular disease in the post-operative period. But in the long run, these patients may have worsened kidney function following radical nephrectomy, resulting in serious consequences for their long-term health. The bias in women is less clear, but may be based on the way surgeons interpret preoperative laboratory tests that may suggest women have better renal function than they actually do.
Selection bias for patients undergoing nephrectomy for small renal tumors
W. C. Huang, E. B. Elkin, P. Russo
Introduction: The incidence of renal tumors (RTs) continues to rise each year, the majority of which are small localized incidental RTs. Despite the known renal functional benefits of partial nephrectomy (PN) over radical nephrectomy (RN) and equivalent oncology outcomes, PN is under-utilized and RN is performed for most of patients with small RTs. We analyzed a population-based cohort of patients with small RTs to identify pre-operative factors predictive of RN vs PN.
Methods: Using Surveillance, Epidemiology and End Results (SEER) cancer registry data linked with Medicare claims, we analyzed variables hypothesized to predict type of surgery between 1995 and 2002. Demographic factors included age at diagnosis, year of surgery, race, marital status, urban-rural location, and economic status. Relevant co-morbid conditions such as diabetes and cardiac disease were identified from diagnosis codes in inpatient, outpatient and physician claims in the year prior to diagnosis. Chi-square statistics and multivariable logistic regression were used to estimate the effects of each characteristic on the likelihood of receiving RN vs PN.
Results: 2,547 patients (81%) underwent RN and 556 (19%) underwent PN. Patients undergoing PN were more likely to be younger, male, married and treated at a later date (year of surgery). There were no differences in the type of surgery based on geographical location, economic level or race. There were no statistically significant differences in pre-existing co-morbidities between the 2 cohorts except for renal insufficiency and cerebrovascular disease. Adjusting for both demographic and co-morbid conditions, factors predictive of RN included age at surgery (OR - 1.43, p<0.001), female gender (OR - 1.31, p = 0.011) and cerebrovascular disease (OR - 1.413, p = 0.019). Factors predictive of PN included the year of surgery (OR - 0.841, p < 0.001) as well as renal insufficiency (OR - 0.66, p = 0.009)
Conclusions: PN continues to be under-utilized for small RTs. For uncertain reasons, PN is not evenly offered to all sub-populations of patients. Elderly patients, women and those with pre-existing cerebrovascular disease can also benefit from PN. Increased education and training in PN is needed to reverse this trend.
Disclosures for Research Team: Nothing to disclose.
***
Disclosures for Moderator Howard M. Sandler, MD, MS: Honoraria from Genentech, General Electric and Sanofi-Aventis; Research funding from Cytogen, Dendreon and Genentech; Other remuneration from Sanofi-Aventis.
Attribution to the 2008 Genitourinary Cancers Symposium is requested in all news coverage
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About the American Society of Clinical Oncology (ASCO)
The American Society of Clinical Oncology (ASCO) is the world’s leading professional organization representing physicians who care for people with cancer. With more than 25,000 members, ASCO is committed to improving cancer care through scientific meetings, educational programs and peer-reviewed journals. For ASCO information and resources, visit www.asco.org/presscenter. Patient-oriented cancer information is available at www.plwc.org.
About the American Society for Therapeutic Radiology and Oncology (ASTRO)
ASTRO is the largest radiation oncology society in the world, with more than 9,000 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to improving patient care through education, clinical practice, advancement of science and advocacy. For more information on ASTRO, visit www.astro.org. For more information on radiation therapy as a treatment option, visit www.rtanswers.org.
About the Society of Urologic Oncology (SUO)
The Society of Urologic Oncology (SUO) is the Nation's preeminent professional organization representing urologic oncologists that hold specific expertise in the study and treatment of genitourinary malignancies. In recognition of the multidisciplinary efforts involved in the study and treatment of genitourinary malignancies, the Society seeks to incorporate multiple disciplines in order to improve the care of patients with malignant urologic disease. For SUO information and resources, visit www.societyofurologiconocology.org.
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