In this report, we propose the following hypotheses:
(1) Since the clinical tools used to stage patients are fairly similar for different tumors, the ratio of the rates of synchronous to metachronous metastases should be similar for different tumors.
(1) Since the clinical tools used to stage patients are fairly similar for different tumors, the ratio of the rates of synchronous to metachronous metastases should be similar for different tumors.
Most patients are staged with familiar imaging tools such as CT, magnetic resonance imaging (MRI), and bone scans. Thus the "ability" to detect metastases should be the same for most primary cancers. As a result, the ratio of synchronous to metachronous metastases across various solid tumors should be approximately constant.
(2) Improvements in diagnostic tools should have caused the ratio of synchronous to metachronous metastases to have increased over time.
Staging studies have become more sensitive over time (eg, the introduction of CT in the 1970s, MRI in the 1980s, and positron-emission tomography [PET] in the 1990s), which would be expected to lead to more frequent identification of synchronous metastases. In other words, with more modern imaging techniques, clinicians should be missing fewer metastases during staging, and thus, the ratio of synchronous to metachronous metastases should have increased (Figure 1).
(3) The fraction of patients with either metachronous or synchronous metastases should have declined over time due to increased screening and earlier diagnoses.
Screening for cancer (eg, mammography, PSA checks) may alter the fraction of patients who have metastases, as screening tends to identify patients with disease that is in earlier stages. Thus, the overall incidence of metastatic disease should have decreased (Figure 1). Improvements in systemic chemotherapy also may have contributed to a decrease in apparent pM1 rates by curing patients who initially harbored micrometastases (see below).
To test these hypotheses, we analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute (NCI) from 1973 through 1998.
Analytic Strategy
SEER Data Extracted
Nineteen solid tumors were selected for the study (Table 1). Data were obtained from the SEER database.[1] The SEER program has been collecting clinical, pathologic, and demographic information on cancer patients since 1973, and its database covers about 10% of the US population. The period studied in this paper covered 1973 to 1998 (the final year in which 5-year data were available at the time of this analysis). Tumor types for which the staging methods used were unique (eg, laparotomy for lymphoma or ovarian cancer) and for which the distinction between extensive locoregional disease and systemic disease is indistinct (eg, abdominal seeding with ovarian cancer) were excluded.
The data were extracted using the SEER*Stat 6.1.4 computer program provided by SEER. The "rate" application of the program was used to calculate crude rates, and the "survival" application of the program was used to calculate survival data. The SEER database presents cancer staging in several ways. For this analysis "summary staging" was used. Summary staging is the most basic way of categorizing how far a cancer has spread from its point of origin. There are five main categories in summary stage: in situ, localized only, regional, distant site(s), and unknown/unstaged.[2] For our analysis, local and regional disease were considered to be cM0 and distant disease was considered to be cM1. In situ and unstaged cancers were not included in the analysis.
For patients diagnosed in the years of 1973 and 1998, the following data were extracted for each disease site:
(1) The rate of synchronous metastases (cM1pM1): This is equal to the crude number of patients with known distant disease (cM1) divided by all patients, ie, cM1pM1/(all patients).
(2) The rate of metachronous metastases (cM0pM1): This was estimated from the 5-year mortality for cM0 patients, and is equal to 1 minus the survival rate for cM0 patients at 5 years.
(3) The rate of having no metastatic disease (cM0pM0): This is equal to 100% minus the rates of cM0pM1 minus the rates of cM1pM1.
The SEER database does not directly provide the rate of cM0pM1. However, the registry does provide the fraction of cM0 patients who subsequently die from their disease within 5 years of diagnosis. Since metastatic cancer is the primary cause of mortality for many solid tumors, this rate can be used as a reasonable surrogate for cM0pM1. The situations where mortality often occurs due to locoregional disease will be discussed as well. For the remainder of the discussion, we will use death rates as a surrogate for metastatic rates in cM0 patients.
A 70-year-old man with a history of localized prostate cancer treated with whole-pelvis radiation therapy with a boost to the prostate, in conjunction with androgen deprivation therapy 7 years prior, presented with lower back pain. A bone scan revealed an area of activity in the sacrum. What is the most likely diagnosis?
