Regional Cancer Center

Transcription

1 Southwest Washington Medical Center Regional Cancer Center 2009 Annual Report Site Review Prostate Cancer

2 The Paradox of Prostate Cancer Peter Wasserman, MD; Kathryn Richert-Boe, MD Southwest Regional Cancer Center, Southwest Washington Medical Center, Vancouver, WA In recent years, the incidence of prostate cancer has risen and mortality has decreased. Increased use of screening with prostate specific antigen (PSA) testing is generally accepted to be the cause of the former, but it is controversial what has caused the latter. During 2008, 87 cases were diagnosed at Southwest Washington Medical Center, making it the most common cancer diagnosed among men. This paper examines prevention, screening, diagnostic factors and treatment options, both now and in the future. The paradox of prostate cancer is that while it is the second most common cause of death from cancer among men, most men with prostate cancer do not die from it whether treated or not. For every man whose life is saved by treatment, many others are treated unnecessarily and are subjected to the significant side effects of treatment, impotence and incontinence. Our challenge, then, is to find a way to identify those men who both need therapy and will benefit from it. Correspondence: Peter Wasserman, MD pwasserm@swmedicalcenter.org Southwest Washington Medical Center Regional Cancer Center PO Box 1600 Vancouver, WA Prostate cancer is the most common cancer and the second most common cause of cancer death among American men. 1 Approximately 192,000 men will be diagnosed with prostate cancer in the United States this year, and over 27,000 will die from the disease. In recent years, incidence has risen and mortality has decreased. Increased use of screening with prostate specific antigen (PSA) testing is generally accepted to be the cause of the former, but it is controversial what has caused the latter. 2 Prostate cancer mortality has decreased even in countries where the prevalence of screening is low. Improvements in therapy may also be playing a role. The most important risk factors for prostate cancer 3 are: Race Increasing age Family history for the disease 51% 21% 22% 3% 3% Figure 1: Age at diagnosis of prostate cancer Southwest 2008 The majority of men diagnosed with prostate cancer at Southwest in 2008 were between the ages of (51%). The incidence of prostate cancer is almost 60% higher for African- American men than for Caucasians, and the mortality rate is about twice as high. 1 At Southwest Washington Medical Center, 87 cases of prostate cancer were diagnosed in 2008, making it the most common cancer diagnosed among men. Incidence steadily increased from 1999 to 2002, then decreased some, most likely due to the clearing of prevalent cases by screening. This is consistent with trends seen nationally. 1 (Figure 2) 2009 Annual Report 1

3 Number of Cases Figure 2: Ten-Year Prostate Cancer incidence Data Southwest The number of prostate cancer cases diagnosed at Southwest peaked in Year 2008 Prevention There is no proven means by which fatal prostate cancer can be prevented. The Prostate Cancer Prevention Trial 4 randomized men to receive the drug finasteride or a placebo. Although the incidence of prostate cancer was 6% lower among men randomized to receive finasteride, there was no difference between the groups in prostate cancer mortality. The SELECT trial 5 randomized men to treatment with selenium and/or vitamin E versus placebo. This study is ongoing, but preliminary results have not shown any benefit from this therapy, and there was a nonsignificant increased incidence of prostate cancer among men randomized to vitamin E alone. Observational studies of other prevention strategies, such as dietary changes or lycopene supplementation, have been inconclusive. Southwest Washington Medical Center participated in the Prostate Cancer Prevention Trial and the SELECT Trial. Screening Screening for prostate cancer remains controversial. The tests commonly used to screen for prostate cancer are digital rectal exam (DRE) and prostate specific antigen (PSA.) Two randomized trials using these tests were recently published. The NCI-sponsored Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial 6 showed no reduction in mortality, while the Scandinavian Prostate Cancer Group Trial 7 showed a statistically significant 5% reduction in mortality, thereby adding fuel to rather than quelling the controversy. Several organizations have issued guidelines for prostate cancer screening. The US Preventative Services Task Force concludes that there is too little evidence either for or against screening to offer a recommendation to men under the age of 75, and it recommends against screening men over the age of It suggests that clinicians should discuss the potential benefits and known harms of PSA screening with their patients younger than age 75 years. Men in this age group should be informed of the gaps in the evidence, and their personal preferences should guide the decision of whether to order the test. Similar recommendations are made by The American Urological Association and the American Cancer Society, but these organizations have a more favorable attitude toward screening. 9,10 2

4 Stage 0 Stage Stage 2 Number of Cases Breast Lung/ Bronchus 65 Stage 3 Stage 4 Unknown Colorectal Prostate Melanoma Figure 3: Major Cancers Stage at Diagnosis Southwest, 2008 At Southwest, 65 of 87 prostate cancer cases (nearly 75%) were diagnosed at Stage 2 during When cancer is diagnosed and treated in its earliest stages, the chances for survival are greatest. Prognostic Factors The most important prognostic factors for prostate cancer are the Gleason grade, TNM stage and pretreatment PSA level. 11 The proportion of men diagnosed with early stage disease has increased in the past decade, mainly due to the increased use of screening with PSA testing. At Southwest, only 6% of men diagnosed with prostate cancer had Stage 4 disease at the time of diagnosis (Figure 3). Treatment Options Treatment options for early stage prostate cancer include: Radical prostatectomy (RP), either open, laparoscopic or robotic Radiation therapy (RT,) external beam or Brachytherapy Active surveillance (formerly called watchful waiting) Southwest Washington Medical Center actively promotes research in all areas of cancer treatment. Currently we have two studies specifically for prostate cancer: CyberKnife treatment for early-stage prostate cancer Treatment for hormone-refractory advanced prostate cancer Prostate cancer treatment at Southwest Washington Medical Center, 2008: 87 cases of prostate cancer diagnosed Most common cancer diagnosed among men 6% had Stage 4 (metastatic) disease at the time of diagnosis Surgery alone was the most common treatment (89%) Five-year survival rate is over 90% higher than national data Surgery and radiation therapy While there is currently an ongoing randomized trial comparing surgery no therapy, 12 trials directly comparing surgery with radiation therapy have been attempted, but all have been inadequately powered due to poor accrual. Although there are those with strong opinions on both sides of the argument, the bulk of data suggest that these two treatments are comparable with respect to cure rates and side effects. 13 Treatment with curative intent (RP or RT) is usually recommended for men with high-risk disease who have a 2009 Annual Report 3

5 life expectancy of at least ten years. Active surveillance is usually reserved for men with low-risk disease, those with other serious co-morbid conditions, and the very elderly. At Southwest, surgery alone was the most common treatment, provided to 73 of 82 (89%) men with early stage disease. (Refer to Table 1: Prostate Cancer First Course Treatment: Southwest, 2008.) Table 1: Prostate Cancer First Course Treatment Southwest, 2008 Type of Treatment Number of Patients Biopsy only 1 Surgery alone 73 Radiation alone 3 Hormones alone 1 Surgery/Hormones 2 Surgery/Radiation 1 Surgery/Radiation/Hormones 1 Radiation Therapy/Hormones 4 Endocrine Surgery 1 For men who have been treated with curative intent who have rising PSA levels and no other evidence for disease, salvage therapy with the other modality may be curative. 14,15 Salvage therapy is more likely to be successful in men with less advanced disease at presentation and a long interval from initial local therapy to PSA failure. Hormonal therapy For men with metastatic cancer, androgen deprivation therapy (ADT) is the initial treatment of choice. 16 This usually consists of a gonadotropin-releasing hormone (GnRH) agonist with or without an antiandrogen. (The GnRH agonist binds to and down-regulates the pituitary gonadotropin-producing cells. The antiandrogen binds to androgen receptors and competitively inhibits their interaction with testosterone.) When given together, they create complete androgen blockade (CAB). Whether CAB is superior to single-agent therapy or whether ADT should be continuous or intermittent remain controversial. Orchiectomy (surgical castration) is as effective as GnRH agonist therapy, but most men prefer a pharmacological approach. Second-line hormonal therapy can include ketoconazole, corticosteroids, estrogens, or megestrol. Abiraterone, an inhibitor of cytochrome P450, is a new oral antiandrogen drug that has been very promising in early clinical trials. 17 Palliative chemotherapy Despite high response rates (>90%), nearly all prostate cancers eventually become unresponsive to hormonal therapy. Palliative chemotherapy, usually with docetaxel, can then be tried. 18 Mitroxantrone and ixabepilone also have activity against hormone-refractory prostate cancer. 19 A promising approach is the identification of molecular markers in prostatic cancer tissue at the time of diagnosis that can predict for either good or poor outcome. 4

6 100 Figure 4: Survival Comparison by five-year Prostate Cancer Southwest vs. National Oncology Database (Observed Survival) The survival rate for Southwest s prostate cancer patients followed national trends through year three. Southwest prostate cancer patients faired better in years four and five versus the national rate. Percentage Southwest National 50 1 st year 2 nd year 3 rd year 4 th year 5 th year Figure 5: Five-Year Survival Comparison by Stage Prostate Cancer Southwest vs. National Oncology Database (Observed Survival) The survival rate for Southwest s prostate cancer patients followed national trends, with the exception at Stage 4, where Southwest s patient survival rate was better than the national rate. Percentage Surviving Southwest National Stage I Stage II Stage III Stage IV The Future In the era of PSA screening, the proportion of men diagnosed with Stage 4 disease is low, and the 5-year survival of men with prostate cancer is very high (>90%.) At Southwest, only 5 of 87 men (6%) were diagnosed with metastatic disease. Five-year survival was over 90% for the entire cohort. This was significantly better than that seen in the rest of the nation (Figure 4). The paradox of prostate cancer is that while it is the second most common cause of death from cancer among men, most men with prostate cancer do not die from it whether treated or not. For every man whose life is saved by treatment, many others are treated unnecessarily and are subjected to the significant side-effects of treatment, impotence and incontinence. Our challenge, then, is to find a way to identify those men who both need therapy and will benefit from it. A promising approach is the identification of molecular markers in prostatic cancer tissue at the time of diagnosis that can predict for either good or poor outcome. 20 This could allow us to better select who does and does not need treatment Annual Report 5

7 Southwest Regional Cancer Center Registry Data Summary 2008 Southwest Washington Medical Center s Cancer Registry accessioned 1,191 new cases that were diagnosed in 2008 and provided follow-up data on over 25,000 primaries gathered in our system. These data, including demographics, staging and treatment, are reported to the Washington State Cancer Registry and the National Cancer Database (NCDB), for use in monitoring cancer incidence and treatment trends in our state and the nation. Comparative Cancer Incidence 2008 In 2008, breast cancer was the number one cancer incidence site at Southwest accounting for 26 percent of all incidences exceeding both Washington state (13%) and national (13%) percentages. Southwest Washington State National Site Number Percent Number Percent Number Percent Breast % 4,140 13% 182,460 13% Lung & Bronchus % 4,110 13% 215,020 15% Colorectal 98 8% 2,850 9% 148,810 10% Prostate 87 7% 4,990 15% 186,320 13% Melanoma 57 5% 1,900 6% 62,4 4% Bladder 52 4% 1,5 5% 68,810 5% Non-Hodgkin Lymphoma 50 4% 1,590 5% 66,120 5% Uterus 48 4% 850 3% 40,100 3% Kidney/Renal Pelvis 32 3% * * 54,390 4% Thyroid Gland 29 3% * * * * Other % * * * * Total % 32,3 100% 1,437,1 100% *Washington State and National Data from ACS Cancer Facts and Figures

8 Southwest Primary site table 2008 Breast and lung cancer were most frequently identified as the primary cancer sites at Southwest in Primary Site Number of cases Percent Oral Cavity and Pharynx % Tongue 4 0.3% Salivary Glands 5 0.4% Gum & Other Mouth 1 0.1% Nasopharynx 2 0.2% Tonsil 8 0.7% Digestive System % Esophagus % Stomach % Small Intestine 3 0.3% Colon % Rectum and Rectosigmoid % Anus and Anal Canal 5 0.4% Liver & Intrahepatic Bile Duct 5 0.4% Other Biliary 8 0.7% Pancreas % Peritoneum, Omentum & Mesentery 2 0.2% Other Digestive Organs 1 0.1% Respiratory System % Nasal Cavity 2 0.2% Larynx 4 0.3% Bronchus and Lung % Trachea, Mediastinum & Other Respiratory 1 0.1% Bones and Joints 2 0.2% Soft Tissue (including Heart) 8 0.7% Skin excluding Basal & Squamous % Malignant Melanoma Skin % Other Non-epithelial Skin 5 0.4% Breast % Female Breast % Male Breast 3 0.7% Primary Site Number of cases Percent Female Genital System % Cervix % Corpus Uteri % Ovary % Vagina 1 0.1% Vulva % Other Female Genital 2 0.2% Male Genital System % Prostate % Testis 4 0.3% Penis 2 0.2% Urinary System % Urinary Bladder % Kidney & Renal Pelvis % Ureter 2 0.2% Eye & Orbit 2 0.2% Brain & Other Nervous System % Brain % Other Nervous System % Endocrine System % Thyroid gland % Other Endocrine (including Thymus) % Lymphomas % Hodgkin s lymphoma (nodal) 7 0.6% Non-Hodgkin s lymphoma (Nodal=37, Extranodal=13) % Myeloma 6 0.5% Leukemia % Lymphocytic Leukemia 7 0.6% Myeloid & Monocytic Leukemia 6 0.5% Mesothelioma 3 0.3% Ill-Defined/Unspecified % 2009 Annual Report 7

9 Southwest frequency of cancer by gender 2008 Bladder cancer was more often sited in men (45) in relation to women (7) at Southwest in REFERENCES 1. Jemal A, Siegel R, Ward E, et al. Cancer Statistics, CA Cancer J Clin: , Esserman L, Shieh Y, Thompson I. Rethinking screening for breast cancer and prostate cancer. JAMA 302: , Gronberg, H. Prostate cancer epidemiology. Lancet 361: , Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. NEJM 349: , Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301:39-51, Andriole GL, Crawford ED, Grubb RL III, et al. Mortality results from a randomized prostate cancer screening trial. NEJM 360: , Schroder FH, Hugosson J, Roobol MJ, et al. ERSPC Investigators. Screening and prostate cancer mortality in a randomized European study. NEJM 360: , Screening for Prostate Cancer Recommendation Statement AUA New Guidelines on Prostate Cancer Screening. psa-rising.com/mednews/component/content/article/38-screening/78- aua-new-guidelines-on-prca-screening 10. American Cancer Society Guidelines for the Early Detection of Cancer. cancer_detection_guidelines_36.asp 11. Steyerberg, EW, Roobol, MJ, Kattan, MW, et al. Prediction of indolent prostate cancer: Validation and updating of a prognostic nomogram. J Urol 177: , Wilt TJ, Brwer MK. The Prostate Cancer intervention Versus Observation Trial (PIVOT). Oncology 11: , Thompson, I, Thrasher, JB, Aus, G, et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol177:2106, Trock, BJ, Han, M, Freedland, SJ, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA 299: , Nguyen, PL, D Amico, AV, Lee, AK, Suh, WW. Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature. Cancer 110: , Loblaw, DA, Mendelson, DS, Talcott, JA, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2007 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol 25: , Attard G, Reid AHM, A;Hern R, et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castrationresistant prostate cancer. JCO 27: , Tannock, IF, de Wit, R, Berry, WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351: , Rosenberg, JE, Weinberg, VK, Kelly, WK, et al. Activity of secondline chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients: randomized phase 2 study of ixabepilone or mitoxantrone and prednisone. Cancer110: , Klotz L. Active surveillance for prostate cancer. World J Urol 26: ,