The results of prostate carcinoma screening in the U.S. as reflected in the surveillance, epidemiology, and end results program.

BACKGROUND: The rapid escalation in the incidence of prostate carcinoma between the years 1988 and 1992 has been attributed to prostate specific antigen screening. There have been concerns regarding the possible diagnosis and treatment of insignificant tumors in the absence of randomized, controlled trial evidence of a decrease in mortality. Descriptive studies suggest that serial screening decreases the detection of advanced disease. In November 1996, the National Center for Health Statistics recorded a decrease in prostate carcinoma mortality. METHODS: The basis of this analysis is 208,234 prostate carcinoma cases diagnosed between 1973 and 1993 in population-based Surveillance, Epidemiology, and End Results registries. The general staging system was used rather than that of the American Joint Committee on Cancer to permit observation of long term trends. Grade incorporating Gleason scores was used as an indication of the significance of the prostate carcinoma. Age-adjusted survival rates were used to separate prostate carcinoma deaths from deaths due to other causes. RESULTS: The increase in the incidence of prostate carcinoma has been greater than for any other malignancy. The increase was largely in Grade 2 significant tumors and not in Grade 1 (15%) insignificant tumors. There was a decrease in the detection of advanced disease. After the peak incidence in 1992, a progressive decrease to near baseline levels occurred. Approximately 38% of all deaths were from prostate carcinoma. Deaths from other causes increased with age. When corrected for death from other causes, men age > 69 years had a greater rate of death from prostate carcinoma than men age 50-69 years. Approximately 61% of all deaths from prostate carcinoma occurred within 5 years of diagnosis and 88% within 10 years. The 10-year survival rate for patients treated by radical prostatectomy was 100%, 78% for patients treated by radiation, and 33% for patients treated with other (noncomparable modalities). CONCLUSIONS: The indirect evidence suggested that prostate carcinoma screening of men ages >50 years decreased the incidence of distant disease, which influences the mortality rate.

Twenty-year follow-up of the breast cancers diagnosed during the Breast Cancer Detection Demonstration Project.

This study reports on the 20-year follow-up of the women diagnosed with breast cancer in the Breast Cancer Detection Demonstration Project (BCDDP) between 1973 and 1980. This project provided 5 years of screening with physical examination and two-view mammography for 280,000 volunteer women across the United States. Based on a 96% follow-up from 1993 to 1995 of the 4,051 women with breast cancer available for analysis, 2,658 (66%) were alive and 1,393 (34%) were dead. A high proportion of the cancers were detected by mammography alone, and 28.6% of all the cancers were smaller than 1.0 cm. Survival rates were calculated by life table method with deaths from breast cancer as the outcome. The adjusted survival rate for the entire group was 80.5%, and the observed survival rate was 61.7%. Adjusted and observed survival rates were 97.2% and 78.5%, respectively, for women with non-invasive cancers and 78.2% and 59.3%, respectively, for those with invasive cancers. Lymph node status and the size of the cancer at diagnosis were prognostic indicators of survival in the BCDDP Women with invasive cancers and negative lymph nodes had an 85.5% breast cancer survival rate and a 65.6% observed survival rate. Adjusted survival rates for women with invasive breast cancers were 90.2% for cancers smaller than 1 cm, 80.5%, for cancers 1.0 to 1.9 cm, 70.5% for cancers 2.0 to 4.9 cm, and 60.6% for cancers larger than 5 cm. Women 40 to 49 years of age demonstrated a greater survival with noninvasive or invasive cancers smaller than 5.0 cm compared with women 50 to 59 and 60 to 69 years of age at diagnosis. These results from the BCDDP are discussed in the context of the recent decline in breast cancer incidence and mortality in the United States.

Twenty-year follow-up of minimal breast cancer from the Breast Cancer Detection Demonstration Project.

Since the 1960s, the potential benefits of early detection of breast cancer through screening with physical examination and mammography have been studied. In a mass screening study begun in 1973 by the Breast Cancer Detection Demonstration Project (BCDDP), mammography detected 90% of the cancers that were diagnosed. Of the women aged 35 to 74 years from the BCDDP study who were diagnosed with minimal breast cancer, the 20-year cumulative breast cancer survival rates were 95.8% for 469 women with in situ breast cancer and 82.8% for 769 women with invasive breast cancers 1 cm or smaller in size.

Benefit of screening mammography in women aged 40-49: a new meta-analysis of randomized controlled trials.

Eight randomized controlled trials (RCTs) of screening mammography have been conducted involving women aged 40-49 at entry. Current data are now available from these trials at 10.5 to 18 years of follow-up (average follow-up time: 12.7 years). Meta-analysis has been performed using a Mantel-Haenszel estimator method to combine current follow-up data from the eight RCTs of mammography that included women aged 40-49 at entry, including new follow-up data presented at the NIH Consensus Development Conference held January 21-23, 1997. Combining the most recent follow-up data on women aged 40-49 at entry into all eight RCTs yields a statistically significant 18% mortality reduction among women invited to screening mammography (relative risk: 0.82; 95% confidence interval: 0.71-0.95). Combining all current follow-up data on women aged 40-49 at entry into the five Swedish RCTs yields a statistically significantly 29% mortality reduction among women invited to screening (relative risk: 0.71; 95% confidence interval: 0.57-0.89). Meta-analysis including the most recent follow-up data from all eight RCTs involving women aged 40-49 at entry demonstrates for the first time a statistically significant mortality reduction due to regular screening mammography in women of this age group.

Prostate cancer facts and fiction.

1. The observed increase in prostate cancer incidence followed by a decrease, was not an epidemic, but the result of generalized prostate cancer screening in the United States. 2. The increase showed a shift in stage, to mainly early disease in grade 2 (Gleason's 4-6) clinically significant cancers with a decrease in advanced disease. 3. There was an increase in the use of radical prostatectomy, mainly in men 40 to 75 years of age with a 10-year relative survival rate of 100%. It appears that 15% were grade 1 cancers and in the absence of more information may have been clinically unimportant. 4. There was a 20% increase in the overall relative survival rate for prostate cancer. 5. There was a decrease in the incidence of advanced disease followed by a 6.3% decrease in the United States mortality rate for prostate cancer. 6. It appears that an annual PSA blood test and a DRE on all men over 50 years of age followed by appropriate treatment has decreased deaths from prostate cancer.

The fall in incidence of prostate carcinoma. On the down side of a prostate specific antigen induced peak in incidence--data from the Utah Cancer Registry.

BACKGROUND: In the 1980s, prostate specific antigen (PSA) came into wide use as a prostate carcinoma screening and detection method in the United States. Following the introduction of PSA, the age-adjusted incidence of prostate carcinoma reported by the Surveillance, Epidemiology, and End Results (SEER) program in the United States rose rapidly (from 84.4/100,000 in 1984 to 163/100,000 in 1991). When an increase in incidence is observed following the introduction of a screening method, a subsequent decrease in incidence may be expected as prevalent cases are removed from the population (a cull effect). Incidence rates may also fall due to factors such as decreased intensity of screening. The Utah Cancer Registry data were examined for a decrease in prostate cancer incidence. METHODS: We tracked age-adjusted prostate carcinoma incidence trends from the population-based Utah Cancer Registry and compared them with rates from the SEER national registry. RESULTS: A rapid and highly correlated rise in prostate carcinoma incidence has been observed in both SEER and Utah incidence rates between 1988 and 1991, the last year for which SEER data are available. In 1992, Utah incidence rates peaked at 236.2 per 100,000. In 1993 and 1994, Utah incidence rates fell to 195.0, and an estimated 164.0 per 100,000, respectively. CONCLUSIONS: Population-based data from the Utah Cancer Registry indicates that the incidence of prostate carcinoma is decreasing rapidly after a similarly rapid increase.

Efficacy of breast cancer screening by age. New results from the Swedish Two-County Trial.

BACKGROUND: Several studies have found a smaller effect of breast cancer screening on breast cancer mortality in women aged younger than 50 years compared with older women. Various possible reasons have been suggested for this, but none firmly is established. METHODS: The Swedish Two-County Study is a randomized trial of breast cancer screening of women aged 40-74 years, comprising with 133,065 women with a 13-year follow-up of 2467 cancers. The Breast Cancer Detection Demonstration Project (BCDDP) is a nonrandomized screening program in the United States, with a 14-year follow-up of 3778 cancers in women aged 40-74 years. The Swedish results by age were updated. The lesser effect of screening at ages 40-49 years was investigated in terms of sojourn time (the duration of the preclinical but detectable phase) size, lymph node status, and histologic type of the tumors diagnosed in the Swedish Study and their subsequent effect on survival using survival data from both studies. RESULTS: In the Swedish Trial, a 30% reduction in mortality associated with the invitation to screening of women aged 40-74 years was maintained after 13-years of follow-up. The reduction was 34% for women aged 50-74 years and 13% for women aged 40-49 years. Results indicated that the reduced effect on mortality for women aged 40-49 years was due to a differential effect of screening on the prognostic factors of tumor size, lymph node status, and histologic type. The mean sojourn times in the age groups 40-49 years, 50-59 years, 60-69 years, and 70-74 years were 1.7, 3.3, 3.8, and 2.6 years, respectively. CONCLUSIONS: These results suggest that much, although not all, of the smaller effect of screening on mortality in women aged 40-49 years is due to faster progression of a substantial proportion of tumors in this age group and the rapid increase in incidence during this decade of life. It is concluded that the interval between screenings should be shortened to achieve a greater benefit in this age group. It is estimated that a 19% reduction in mortality would result from an annual screening regime.

Benefit of mammography screening in women ages 40 to 49 years. Current evidence from randomized controlled trials.

BACKGROUND: Eight randomized controlled trials (RCTs) of screening mammography were conducted involving women ages 40 to 49 years at entry. Current data gathered for periods ranging from 7 to 18 years of follow-up are available from these trials. METHODS: Meta-analyses were performed using a Mantel-Haenszel estimator method to combine current follow-up data from the eight RCTs of mammography that included women ages 40 to 49 years. RESULTS: Combining all current data on women ages 40 to 49 years at entry into the trials yielded a 16% [corrected] benefit from screening mammography, without statistical significance at the 95% confidence level. Combining all data on women ages 40 to 49 years at entry, excluding results from the Canadian National Breast Screening Study, yielded a 24% [corrected] benefit to women invited for screening, with statistical significance at the 95% confidence level. CONCLUSIONS: These results suggest that screening mammography in women ages 40 to 49 years at entry can reduce mortality from breast cancer when combined with adequate follow-up.

Highlights of the evidence of benefit for women aged 40-49 years from the 14-year follow-up of the Breast Cancer Detection Demonstration Project.

Randomized breast cancer screening trials are helpful in establishing evidence of benefit when they yield statistically significant results. The results of individual randomized screening trials can vary greatly depending on the quality of the images, the frequency of screening, compliance, contamination, sample size, and the length and adequacy of follow-up. For women 40-49 years of age at entry the first randomized breast cancer screening trial, the Health Insurance Program of Greater New York (HIP), showed a statistically significant decrease of 24% in breast cancer mortality at 18 years of follow-up, virtually the same as the 23% decrease seen in women 50-59 years of age. At 10-12 years of follow-up, five of seven randomized trials have shown nonstatistical decreases in breast cancer mortality. No trials with fewer than 8 years of follow-up have shown a decrease in mortality for women 40-49 years of age; whereas seven trials have shown a decrease for women older than 50 years of age. The largest study on the screening of women aged 40-49 (93,471) was the Breast Cancer Detection Demonstration Program (BCDDP). This demonstration program was not a randomized trial but has yielded indirect supportive evidence for the screening of women aged 40-49, by comparing age group results. Three highlights of these studies are presented: (1) Mammography in the BCDDP (1970s) was improved greatly compared to that in the HIP study (1960s). Mammography detected 40% of the cancers in women 40-49 years of age in the HIP compared to 90% in the BCDDP. In women 50-59 years of age, mammography detected 60% of cancers in the HIP but 92% in the BCDDP. (2) Using annual two-view mammography plus clinical breast examination after the first screen of women 45 years of age and older, subsequent detection rates were virtually the same for all age groups. The number of women screened annually yields slightly more than two breast cancers per 1000 women, regardless of age group. (3) Similar types, sizes, stage distributions, and survival and case fatality rates were demonstrated in women aged 40-49, 50-59 and 60-69 years.

Survival advantage differences by age. Evaluation of the extended follow-up of the Breast Cancer Detection Demonstration Project.

BACKGROUND: This study considers breast cancer survival patterns by age group among women diagnosed in the Breast Cancer Detection Demonstration Project (BCDDP) to provide insight into the nature of breast cancer and suggest a possible explanation as to why the results of the randomized clinical trials differ for women younger than 50 and those 50 or older. Based on the findings of several randomized clinical trials, there is a general consensus that breast cancer screening provides a significant benefit for women aged 50-69. From these trials, there is little evidence of a short term benefit and uncertainty regarding any long term benefit of mammographic screening for women aged 40-49. METHODS: The BCDDP was not a randomized trial, but a nationwide breast cancer screening program conducted between 1973-1980, in which all participants received annual physical and mammographic examinations. Using the BCDDP data, this study calculated 14-year breast cancer survival among 4051 women diagnosed with breast cancer between 1973 and 1980 and followed through 1988 and 1989. RESULTS: In all, 598 women died of breast cancer, resulting in an overall 14-year breast cancer survival of 83.4% (standard error = 0.007). Breast cancer survival varied by tumor type, lymph node status, tumor size, and stage at diagnosis. For most of the cases, however, both the distribution and breast cancer survival rates were similar for women aged 40-49, 50-59, and 60-69 across all prognostic indicators. Only breast cancer survival among women with invasive breast cancer who had a primary tumor 5 cm or larger or with positive lymph nodes differed by age, with women aged 60-69 at diagnosis having poorer survival. Analyses by modality of detection conducted in a subset of 2739 cases indicated that the 34.6% of the cases detected by mammography alone had the highest overall breast cancer survival rates (90.9%), while the 32.2% of the cases detectable by both physical examination and mammography had the lowest breast cancer survival (79.0%). Overall, women diagnosed with breast cancer in the BCDDP had a survival advantage if diagnosed with either a smaller tumor or no positive lymph nodes, or if their breast cancer was detected by mammography alone. For women with large tumors (> or = 5 cm), the survival was 80.8% for ages 40-49, 72.1% for ages 50-59, and 61.7% for ages 60-69. DISCUSSION: Due to the higher breast cancer survival rates among women aged 40-49 with poorer prognostic characteristics, the breast cancer survival advantage for having a smaller tumor, no positive lymph nodes, or breast cancer detected by mammography alone was lower for women aged 40-49 than women aged 50 or older at diagnosis. These differences in survival advantage may help to account for the differences in mortality by age in the randomized clinical trials.

Breast cancer detection guidelines for women aged 40 to 49 years: rationale for the American Cancer Society reaffirmation of recommendations. American Cancer Society.

Over the past year, the National Cancer Institute has altered its guidelines for early breast cancer screening by omitting any recommendation for mammography and clinical breast examination for women aged 40 to 49 years, while the American Cancer Society has reaffirmed its recommendation for these screening procedures in this age group. This article reviews the process and some of the evidence the American Cancer Society has relied upon in reaffirming its recommended guidelines for early breast cancer detection.

The Canadian National Breast Screening Study. An appraisal and implications for early detection policy.

The recent reports from the Canadian National Breast Screening Study (CNBSS) address the effectiveness of breast cancer screening for women in the 40-49 age group and the benefit of adding mammography to standard clinical breast examination in women aged 50-59. Overall, the CNBSS results do not show reductions in breast cancer mortality after seven years of follow-up in either age group. The CNBSS is an important study that includes a large number of women, rigorous procedures, and thorough follow-up, but there are several caveats to interpreting these results. The study results reported to date are based on small numbers of end point events. There are questions about the effectiveness of the randomization procedures in creating cohorts that initially were at equal risk of breast cancer-related death. It also has been observed that the quality level of mammographic screens obtained at the beginning of the study were not as high as those obtained later. Future reports from the CNBSS are planned and may provide additional data helpful in interpreting the results.

Screening for cancer of the aerodigestive tract.

In the United States, cancer of the oral cavity is the only region of the aerodigestive tract that lends itself to routine screening of the asymptomatic population older than 50 years. Although the incidence and mortality rate for oral cancer is nearly double that of cancer of the cervix (30,300 versus 13,500 and 7950 versus 4400, respectively), conducting a pelvic examination and Pap smear appears more acceptable than looking in the mouth. The inspection of the oral cavity should be part of every physical examination in the dentist's or the physician's office, particularly in patients older than 50 years who are heavy users of tobacco and alcohol. Ninety percent of all squamous cell cancers arise from the floor of the mouth, the ventrolateral aspect of the tongue, and the soft palate complex. The detection rate is increased from approximately 1 per 1000 in asymptomatic individuals older than 50 years to 1 per 200 in high-risk smokers and drinkers and to 1 in 7 for individuals once treated for oral cancer. Screening detects earlier stage cancers, for which treatment results in higher survival rates. While no randomized screening trials with a mortality end-point have been conducted (or are likely), there is evidence that population-based case-fatality rates are lower in races treated with earlier stages of oral cancer. This evidence is of little solace when the majority of patients are diagnosed with advanced disease when symptoms appear, rather than through screening at an earlier stage when asymptomatic. In one study, 94% of patients with oral cancer were seen by a doctor within the previous year. The average oral cancer patient had 10.7 physician encounters within 3 years of the diagnosis. In the United States, the early detection of cancers of the larynx and esophagus should be based upon early symptoms rather than on screening. A routine oral screening examination should be a part of every physical examination by a doctor or a dentist. It will detect earlier cancers and save lives.

Mammographic screening: efficacy and guidelines.

Over the past year, concerns regarding breast cancer screening guidelines and the benefits of mammography have been raised. These concerns were fueled by a leak of information from the Canadian National Breast Screening study that suggested first an increase in mortality in women aged 40 to 49 years and then, after further investigation, no change in mortality for women screened with mammography as compared with those who relied on physical examination. No benefit from the addition of mammography to physical examination was reported for women aged 50 to 59 years. Published data demonstrate poor mammographic images in the first 3 years of the study. Direct evidence of benefit in women aged 40 to 49 years is available only in the Health Insurance Plan trial in which two-view mammography plus physical examination resulted in a delayed reduction in mortality equal to that in older women. The other trials, except for the Canadian trial, used less sensitive protocols and frequently used single-view mammography at 2- or 3-year intervals. Evidence from the Breast Cancer Detection Demonstration Project suggested benefit in screening women aged 40 years or older with annual mammography and physical examination. This paper reviews 11-year results from the Swedish two-county study and the results of other studies and discusses factors related to frequency, sensitivity, and lead-time.

Screening and early diagnosis.

Although colorectal cancer is the second leading cause of death in the US, the majority of diagnoses are made at an advanced stage, and screening detects 70% at an early stage, controversy has existed because of a lack of experimental controlled trial evidence showing a decrease in mortality. Indirect and now direct evidence supports the current screening guidelines of the American Cancer Society and the National Cancer Institute as reasonable and should be continued.

Staging patterns and early cancer detection.

There is a great deal of indirect, nonexperimental evidence that a pattern of earlier-stage disease at diagnosis has a better outcome. Increased early detection activities can change, these stage patterns while various biases and the question of generalizability need to be kept in mind in their interpretation. The indirect evidences of possible benefit from early detection activities includes an increase in the number of cases detected, a pattern of more early- and less advanced-stage cases, an increase in the overall site-specific survival rate, and a decrease in the case fatality rate. Unless these intermediate markers are favorable, it is unlikely that early detection will reduce mortality. In addition, one should also differentiate a reduced incidence or a change in treatment as a cause for reduced mortality.