Prostate Cancer Anatomy Paul A. Godley, MD, PhD Cancer Incidence, Males Prostate Cancer Epidemiology 24 Estimated New Cancer Cases Melanoma 29,9 Oral 18,55 Stomach 13,4 Leukemias 19,2 Kidney 22,8 Lymphomas 33,18 Bladder 44,64 Colorectal 73,62 Pancreas Lung 93,11 Prostate 23,11 American Cancer Society, 24 Prostate Cancer Incidence per 1, Males USA - Black USA - White Canada Sweden W. Australia Switzerland Norway Los Angeles - Japanese France Finland New Zealand - non-maori Netherlands Germany Scotland Denmark S Ireland England Spain Costa Rica Israel Yugoslavia Los Angeles - Chinese Poland Italy Singapore - Chinese Japan India Hong Kong China 55 53 49 48 47 44 41 38 36 36 31 31 3 28 27 27 24 21 2 16 12 1 9 8 8 2 65 11 137 Parkin D, Whelan SL, Feday J, Young J. Cancer Incidence in Five Continents,Vol. VII. Lyon: International Agency for Research on Cancer, #143, 1997. 2 4 6 8 1 12 14 16 Prostate Cancer Incidence per 1, males Prostate Cancer Epidemiology Cancer Mortality, Males Incidence Trends by Race 1973-1999 Age-adjusted Incidence per 1, Males 3 25 2 15 1 5 Black Males White Males 23 Estimated Cancer Deaths Liver 9,2 Esophagus 9,9 Stomach 7, Bladder 8,6 Leukemias Lymphoma 12,9 Pancreas Brain Kidney Colorectal 28,3 Lung 88,4 Prostate 28,9 1973 1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 Year of Diagnosis American Cancer Society, 23 Page 1
Prostate Cancer Epidemiology Age-adjusted Prostate Cancer Death Rates by State and Race 1984-1988 Wash D.C. North Carolina Virginia Florida Maryland South Carolina Georgia Indiana Ohio California New Jersey Illinois New York Pennsylvania Alabama Tennessee Michigan Louisiana Connecticut Kentucky Washington Missouri Massachusetts Mississippi Texas Arkansas White Black 1 2 3 4 5 6 Massachusetts Medical Society, 1992 U.S. Cancer Mortality, Males 1991-1995 Percent Change 1 5-5 -1-15 -2.1-4.3-8.7 National Center for Health Statistics -6.7 All Ages <65 65+ -13.8-2.6-6.3-7.4-3.8-7 -5.2-7.6-1.4 All Sites Lung Prostate Colorectal Oral Lymphatic -15-5.9 4.1.4 6.3 U.S. Cancer Mortality, Prostate Cancer 1971-9 vs. 1991-95 4 35 3 1971-9 Percent Change 25 2 15 1 5 19.6 1991-95 34.7-5 -1 White Men -6.7 Black Men -4.5 National Center for Health Statistics Rationale Stage-standardized variations in the treatment of 251,416 prostate cancer patients diagnosed in the U.S. between 1992 and 1994 by race. 3 Percentage of Patients 29.1 28.8 28.5 29.1 white 25 black 23.9 22.3 2 15 1 Rationale Previous studies had assumed that patients receiving identical treatments had similar outcomes. Our goal was to investigate racial disparities in prostate cancer mortality by treatment choice. About 75% of the estimated 22,9 prostate cancers diagnosed in 23 will be clinically localized at the time of diagnosis Several studies of localized prostate cancer, some based in health care systems that lacked financial barriers to treatment, found no differences in survival between black and white patients 5 Watchful Waiting Radiation Therapy Radical Prostatectomy Mettlin CJ, Murphy GP, Cunningham MP, Menck HR. The National Cancer Data Base report on race, age, and region variations in prostate cancer treatment. Cancer 1997; 8:1261-6 Page 2
Previous Studies Biochemical recurrence rates of 148 white (dashed line) and 125 black (solid line) men who underwent radical prostatectomy for prostate cancer as determined by the Kaplan-Meier method. No differences were found in PSA recurrence between the two ethnic groups ( P=.651). Freedland SJ, Jalkut M, Dorey F, Sutter ME, Aronson WJ. Race is not an independent predictor of biochemical recurrence after radical prostatectomy in an equal access medical center. Urology 2;56(1):87-91 SEER Surveillance Epidemiology and End Results (SEER) SEER Program collects data on 12, new cancer cases yearly States of Connecticut*, Iowa, New Mexico, Utah, Hawaii and the metropolitan areas of Detroit*, San Francisco*, Seattle-Puget Sound*, and Atlanta* Hospitals, Laboratories, clinics, physician offices Report incidence rates adjusted to the U.S. 197 standard population Monitor incidence patterns and changes in cancer therapy and patient survival Medicare Provides health insurance coverage for 97% of American age 65 and older Information available through the Medicare program includes health service claims for care provided by Physicians Inpatient hospital stays Hospital outpatient clinics Home health care agencies Skilled nursing facilities Hospice programs Methods Surveillance, Epidemiology and End Results (SEER) tumor registry data were used to identify prostate cancer patients determine their initial treatment follow them for outcomes over time SEER-Medicare linked files Facilitate following cancer patients from their diagnosis beyond their initial treatment window Allow examination of care provided throughout the course of the disease. Provide information about other diseases and conditions that might confound the relationship between race and survival. Study Population Prostate Cancer Cases From 5 Regions Diagnosed 1986-1996, N=14,537 Study Population N=73,424 with age 65 N=11,353 with prior cancer N=93,184 prostate cancer is first cancer included N=4,428 Other races N=68,996 Caucasian or African American N=665 2nd Cancer diagnosed in same month dropped N=3,386 in situ cancer dropped N=92,519 Only prostate Cancer diagnosed that month N=89,133 Invasive Cancer included N=814 Diagnosed at death N=4 No Medicare during study period N=68,182 Diagnosed alive N=68,142 with Medicare coverage included N=72 No month of diagnosis N=88,413 with valid diagnosis month Included N=22,3 Non-surgery, regional or advanced stage N=46,139 Met staging criteria N=14,989 age <65 dropped N=73,424 age 65 included N=2,15 Age 85 N=43,989 Age <85 Study Population Page 3
Staging Issues Staging information in SEER is based on clinical information except for surgical patients, whose staging information is updated with pathological findings If analyses of locally staged surgical patients are conducted, the surgery group will exclude some patients who were initially staged as local but after surgery were reclassified to a more advanced stage To avoid this potential misclassification, we staged all radical prostatectomy and lymphadenectomy patients as local Retained SEER pathological staging information for the multivariate analysis. Patients receiving other treatments or watchful waiting were staged as local using SEER information Follow up Date of death was available in both SEER and Medicare files Medicare dates of death provided the longest follow-up (through 1998) and were used for analyses of all cause mortality. Only SEER data provided the cause of death, SEER death dates were used for analyses of prostate cancer-specific mortality Survival was measured in months from the date of diagnosis to the end of the study period. Covariates No individual measures of socioeconomic status were available SEER data included a number of census-based measures linked to the residence of the patient Three measures were divided into quartiles to adjust for socioeconomic status: The percent of persons of the same race residing in the patient s census tract that had incomes below the poverty level The median income of the census tract The percent of persons of the same race in the census tract that had less than high school education Other Variables SEER site, age at diagnosis, PSA period (1986-1988, pre-psa period; 1989-1991, early PSA period; 1992-1996, recent PSA period), Gleason grade, and stage Comorbidity A modified Charlson index comorbidity score was calculated from hospital discharge diagnoses in Medicare claims Inpatient claims for the year prior to diagnosis were used Only 17,659 subjects had comorbidity information Characteristics of Study Population No. of white No. of black patients patients Characteristic (% of total) (% of total) All patients 38 242 (86.9) 5747 (13.1) Age group, y 65-69 12 839 (33.6) 2149 (37.4) 7-74 13 57 (34.1) 192 (33.1) 75-79 849 (22.2) 1164 (2.3) 8-84 3856 (1.1) 532 (9.3) Era of Diagnosis Pre-PSA (1986-1988) 7489 (19.6) 119 (17.7) Early PSA (1989-1991) 11 122 (29.1) 1356 (23.6) Recent PSA (1992-1996) 19 631 (51.3) 3372 (58.7) Marital status Single 264 (5.4) 673 (11.7) Married 29 442 (77.) 3426 (59.6) Divorced/separated/widowed 4521 (11.8) 1154 (2.1) Not reported/missing 2215 (5.8) 494 (8.6) SEER Site San Francisco 694 (18.1) 1114 (19.4) Connecticut 8363 (21.9) 516 (9.) Detroit 9553 (25.) 2977 (51.8) Seattle 1 532 (27.5) 222 (3.9) Atlanta 289 (7.6) 918 (16.) *Not all percentages add to 1 because of rounding. Two-sided P <.1 (X 2 test). Characteristics of Study Population No. of white no. of black patients patients Characteristic (% of total) (% of total) Treatment Radiation 12 741 (33.3) 1837 (32.) Surgery 12 411 (32.5) 1372 (23.9) Radiation/surgery 267 (7.) 352 (6.1) Nonaggressive 1 42 (27.2) 2186 (38.) Precentage of persons in census tract with less than a high school education -9.5 1 377 (27.1) 25 (3.6) 9.51-16.5 9817 (25.7) 313 (5.5) 16.51-25.5 8936 (23.4) 738 (12.8) 25.51-1 5992 (15.7) 3997 (69.5) Not reported/missing 312 (8.2) 494 (8.6) Median household income, $ 25-23 779 (2.4) 3124 (54.4) 23 1-29 8181 (21.4) 916 (15.9) 29 1-38 9656 (25.2) 652 (11.3) 38 1-1 942 (24.6) 31 (5.4) Not reported/missing 3213 (8.4) 745 (13.) Prostate cancer grade 1 6881 (18.) 952 (16.6) 2 22 482 (58.8) 3 656 (17.) 1156 (2.1) Ungraded 2373 (6.2) 445 (7.7) *Not all percentages add to 1 because of rounding. Two-sided P <.1 (X 2 test). Page 4
Median Survival time and Survival Rates by Race Median Survival time, y (95% CI) 1-year survival rate (95% CI) Patients Black Patients Mortality endpoint White Patients Black Patients White All-cause mortality 9.8 (9.6 to 9.9) 8.1 (7.8 to 8.3).49 (.48 to.5).38 (.36 to.41) Nonaggressive 6.8 (6.6 to 6.9) 5.8 (5.7 to 6.2) 9.32 (.31 to.34).26 (.23 to.28) treatment Radiation therapy 9.4 (9.2 to 9.7) 8.7 (8.4 to 9.3).47 (.46 to.49).42 (.38 to.46) Surgery 12.6 (12.4 to NA ) 1.8 (1. to 11.7).64 (.62 to.65).55 (.51 to.6) Prostate cancer mortality -- --.9 (.89 to.9).84 (.82 to.86) Nonaggressive -- --.87 (.86 to.88).79 (.76 to.83) treatment Radiation therapy -- --.89 (.88 to.9).86 (.83 to.9) Surgery -- --.92 (.92 to.93).88 (.84 to.91) Non-prostate cancer (1.61 (8.8.55 (.54 to.55).45 (.43 to.48) 1.8 to 1.9) 9.1 to 9.6) mortality -- -- *Survival times and rates were obtained from Kaplan-Meier survival estimates. CI = confidence interval; - = median survival time not yet reached. Upper limit to confidence interval is not available because of censoring. Survival Curves by Race and Treatment Overall Survival by Race Median Survival time, y (95% CI) 1-year survival rate (95% CI) Patients Black Patients Variable White Patients Black Patients White Age group, y 65-69 -- (1.3 to 11.6).65 (.63 to.66).55 (.51 to.58) 1.8 7-74 (1.3 8.3 (7.8 to 8.8).53 (.52 to.54).39 (.35 to.43) 1.4 to 1.8) 75-79 7.8 (7.7 to 8.1) 6.3 (6. to 6.9).36 (.35 to.38).24 (.2 to.29) 8-84 5.3 (5.2 to 5.5) 4.8 (4.3 to 5.3).18 (.16 to.2).1 (.6 to.14) Era of diagnosis Pre-PSA (1986-1988) 8.4 (.83 to 8.7) 6.8 (6.3 to 7.2).42 (.41 to.43).32 (.29 to.34) Early-PSA (1989-1991) -- 7.8 (7.3 to 8.3).53 (.51 to.54).39 (.35 to.43) Recent-PSA (1992-1996) -- -- -- -- SEER site San Francisco (9.3 (8. (.48.42 (.38 9.9 to 1.8) 8.7 to 9.3).5 to.52) to.47) Connecticut 8.9 (8.7 to 9.3) 8.7 (7.3 to 9.5).44 (.42 to.46).37 (.28 to.46) Detroit 9.3 (8.9 to 9.6) 7.8 (7.3 to 8.1).46 (.44 to.48).37 (.34 to.4) Seattle 1.7 (1.3 to 11.) 9.4 (8.5 to NA ).54 (.53 to.55).5 (.38 to.61) Atlanta 9.9 (9.3 to 1.8) 7.7 (7.1 to 8.2).5 (.47 to.53).34 (.28 to.39) Marital status Single 9. (8.7 to 9.5) 7.2 (6.5 to 8.2).44 (.41 to.48).32 (.26 to.39) Married 1.3 (1.1 to 1.4) 8.7 (8.3 to 9.1).52 (.51 to.53).43 (.41 to.46) Divorced/separated/widowed 7.3 (7.1 to 7.8) 6.4 (5.9 to 7.).35 (.32 to.37).28 (.23 to.32) *Survival times and rates were obtained from Kaplan-Meier survival estimates. CI = confidence interval; - = median survival time not yet reached; SEER = Surveillance, Epidemiology, and End Results Program. Upper limit to confidence interval is not available because of censoring. Survival Curves for Surgery Cases by Time Period Survival After Prostate Cancer Treatment Survival Curves by Race Page 5
Adjusted Survival After Prostate Cancer Treatment Adjusted Survival After Prostate Cancer Treatment Median Survival time, y 1-year survival rate (95% CI) Patients Black Patients Estimate type White Patients Black Patients White All patients Unadjusted 9.8 8..49 (.48 to.5).38 (.37 to.4) Adjusted 1.4 7.9.52 (.5 to.54).38 (.35 to.41) Surgery patients Unadjusted 12.6 1.4.64 (.63 to.65).53 (.5 to.56) Adjusted -- 11.3.7 (.68 to.71).56 (.52 to.61) *Unadjusted estimates were obtained from Cox proportional hazards survival estimates; adjusted estimates were obtained by the mean covariate level method. CI = confidence interval; - = median survival was not reached. Adjusted for treatment; age; Surveillance, Epidemilogy, and End Results (SEER) Proram site; census tract educational level and median household income; marital stats; cancer grade; PSA era; and comorbidity score. ąadjusted for pathologic stage, age, SEER site, census tract educational level and median household income, marital status, cancer grade, PSA era, and comorbidity score. Conclusions African Americans suffer disparities after all treatment modalities, but most prominently after surgery for localized prostate cancer Racial differences in treatment outcomes become less pronounced over time The consistency of the racial disparity across prostate cancer treatment, PSA era, and cause-specific mortality may suggest a global social or environmental factor that disproportionately diminishes survival among blacks regardless of how mortality is measured Another possible mechanism for these results is a selection process systematically choosing poorer prognosis black patients than white patients for prostate cancer surgery Objective PSA criteria may explain the apparent decline over time in the racial differences in treatment outcomes Next Steps SEER/Medicare analyses including hospital prostatectomy experience SEER/Medicare analyses of prostate cancer relapse-free survival Survey prostate cancer patients Treatment decisions Access to cancer care Investigators Anna Schenck, MSPH, PhD Medical Review of North Carolina, Inc. Victor J. Schoenbach, PhD M. Ahinee Amamoo, MS Michael Symons, PhD Michelle Manning, MPH James A. Talcott, MD, SM Center for Research, Massachusetts General Hospital Cancer Center and Harvard Medical School UNC Center for Health Promotion and Disease Prevention Association of Teachers of Preventive Medicine/ CDC Page 6