Since the first description by Giltman in [
Thus, signet ring prostatic carcinoma (SRPC) is a rare form of adenocarcinoma. Although several small case series have been reported, most of these reports were retrospective reviews from single institutional experiences and focused on the histopathology [
SEER retrieves patient records from multiple locations across the United States and is regarded as a model population-based tumor registry. SEER 9, 13, and 17 registries cover approximately 9.5%, 13.8%, and 26.2% of the total US population, respectively. In this study, we used the SEER data based on the November 2006 submission. Data for this study were obtained from SEER* Stat public-use data files, available on internet or CD-ROM from the National Cancer Institute [
The cases of SRPC were extracted from the SEER on the basis of anatomic site and histology type. All patients over the age of 18 years diagnosed with SRPC in the SEER national cancer registry between January 1980 and December 2004 were evaluated. Cases identified at the time of autopsy or by death certificate only and patients with more than one primary tumor were excluded from the survival analyses.
Patients' social demographic characteristics (i.e., age, race/ethnicity, and marital status) and tumor grade and stage at the time of diagnosis were determined from the SEER database. SEER general summary stage [
Age-adjusted incidence rates and their 95% CIs were calculated for SRPC in all patients, in men and women separately and in each of the 3 broad race categories (whites, blacks, and others). For calculation of the age-adjusted incidence rates, the US general population for the year 2000 was used as a standard population.
Discrete data are reported as frequencies and compared by chi-square and Fisher’s exact tests as appropriate. Continuous data are reported as mean ± SD and compared by student’s
SEER*Stat 6.2.4 (Surveillance Research Program, National Cancer Institute) was used for incidence and limited-duration prevalence analyses. All other statistical calculations were performed by SPSS 12.0 (Apache Software Foundation 2000). Comparative differences were considered statistically significant when the
A total of 588,101 patients with prostate cancer were identified in the SEER 17 registries between January 1980 and December 2004. When we restricted the search to signet ring cell carcinoma histology, a total of 93 patients were identified, representing 0.02% of all patients with prostate cancers.
Using linked population files, the incidence of SRPC as a rate per 100,000 per year, age-adjusted to year 2000 US standard population was calculated. An age-adjusted incidence of 0.0088 per 100,000 was observed in the study periods. Detailed incidence data by time period, gender, and race are included in Table
Age-Adjusted Incidence Rate of Signet Ring Prostate Carcinoma.
Age-adjusted incidence rate* | 95% CI | |
---|---|---|
All | 0.0088 | (0.0065–0.0116) |
White | 0.0077 | (0.0054–0.0107) |
Black | 0.00187 | (0.0085–0.0353) |
Others | 0.0081 | (0.002–0.0206) |
Table
Characteristics of 93 Patients with Signet Ring Prostate Carcinoma (Diagnosed Between January 1980 and December 2004).
Characteristics | Total patients |
---|---|
Age groups, | |
40–50 yrs | 5 (5.4) |
51–60 yrs | 13 (14.0) |
61–70 yrs | 30 (32.2) |
| 45 (48.4) |
Race | |
Black | 14 (15.1) |
White | 68 (73.1) |
Others | 11 (11.8) |
Married | |
Yes | 64 (68.8) |
No | 18 (19.4) |
Unknown | 11 (11.8) |
Grade | |
Moderately-differentiated | 9 (9.7) |
Poorly-differentiated | 74 (79.6) |
Undifferentiated | 3 (3.2) |
Unknown | 7 (7.5) |
PSA | |
Above normal | 29 (31.2) |
Normal | 6 (6.5) |
Unknown | 58 (62.4) |
Stage | |
Local/regional | 72 (77.9) |
Distant | 13 (13.9) |
Unknown | 8 (8.6) |
Year of diagnosis | |
1980–1994 | 22 (23.7) |
1995–2004 | 71 (76.3) |
Prostatectomy | |
Yes | 25 (26.9) |
No | 68 (73.1) |
Radiation | |
Yes | 25 (26.9) |
No | 66 (71.0) |
Unknown | 2 (2.1) |
PSA: prostate specific antigen.
Of the 93 patients, 82.8% patients had high grade (poorly or undifferentiated) histology; 13.9% patients presented with distant stage. Among the patients with known PSA value (
Overall, the median duration of followup was 30 (range 0–238) months, and the median duration of follow-up for censored patients was 2.7 years. Finally, a total 39 of 93 (41.9%) patients died during the followup period.
Cancer-directed surgery was performed in 40 (45%) patients; among them, 25 patients (26.9%) had radical prostatectomy. A total of 25 (26.9%) of the patients received primary radiation therapy, with adjuvant radiation following surgery in 5(5.4%) patients.
In a logistic regression analysis, age, marital status, and tumor stage significantly correlated with radical prostatectomy; the patients who were older, unmarried and had advanced stage tumor were less likely to elect radical prostatectomy. In a separate analysis restricted to patients with local/regional disease, younger age and being married remained independent predictors of radical prostatectomy (Table
Multivariate Analyses of Factors Associated with Receipt of Radical Prostatectomy in Patients with Localized/Regional Stage Signet Ring Prostate Carcinoma.
Characteristics | Group | OR | 95% CI | |
---|---|---|---|---|
Age | Continuous | 0.80 | 0.71–0.90 | |
Ethnicity | White | 1.00 | ||
Black | 3.85 | 0.39–38.0 | 0.25 | |
Others | 1.79 | 0.22–14.4 | 0.58 | |
Marital status | Married | 1.00 | ||
No | 0.12 | 0.02–0.85 | 0.03 | |
Year of Diagnosis | 1980–1994 | 1.00 | ||
1995–2004 | 0.62 | 0.13–2.97 | 0.55 | |
Radiation | No | 1.00 | ||
Yes | 0.10 | 0.01–0.92 | 0.04 |
OR: odds ratio; CI: confidence interval.
Logistic regression analyses of factors associated with radiation therapy were also performed. African Americans were more likely to receive radiation therapy compared to the other races. Prostatectomy receipts were found to be less likely to receive radiation therapy (Table
Multivariate Analyses of Factors Associated with Receipt of Radiation in Patients with Signet Ring Prostate Carcinoma.
Characteristics | Group | OR | 95% CI | |
---|---|---|---|---|
Age | Continuous | 0.97 | 0.92–1.03 | 0.34 |
Ethnicity | White | 1.00 | ||
Black | 8.67 | 1.66–45.36 | 0.01 | |
Others | 0.44 | 0.04–4.54 | 0.49 | |
Year of Diagnosis | 1980–1994 | 1.00 | ||
1995–2004 | 1.27 | 0.35–4.67 | 0.72 | |
SEER stage | Local | 1.00 | ||
Distant | 0.30 | 0.06–1.51 | 0.15 | |
Unstaged | 0.31 | 0.03–3.0 | 0.31 | |
Marital status | Married | 1.00 | ||
No | 0.47 | 0.14–1.62 | 0.23 | |
Prostatectomy | No | 1.00 | ||
Yes | 0.06 | 0.01–0.44 | 0.006 |
OR: odds ratio; CI: confidence interval.
For cancer-specific survival analyses, the cases that were diagnosed at autopsy or on the basis of death certificates only as well as patients with multiple primaries were excluded. A total 81 patients were included in the survival analysis. Table
1-, 3-, and 5-year cancer-specific Survival of Patients with Signet Ring Prostate Carcinoma According to Demographic and Clinical Characteristics.
Characteristics | Cancer-Specific Survival Rate (%) | |||
1-year | 3-year | 5-year | ||
Overall patients | 94.6 | 89.6 | 83.8 | |
Age subgroups | 40–50 yrs | 80 | 60 | 60 |
51–60 yrs | 88.8 | 77.8 | 77.8 | |
61–70 yrs | 94.4 | 94.4 | 85.9 | |
94.7 | 94.7 | 88 | ||
SEER stage | Local | 96.4 | 91.9 | 88.3 |
Distant | 90.0 | 78.8 | 39.4 | |
unstaged | 87.5 | 87.5 | 87.5 | |
Prostatectomy | No | 94.5 | 80.9 | 80.9 |
Yes | 94.7 | 89.2 | 89.2 | |
Year | 1980–1994 | 88.9 | 76.6 | 68.9 |
1995–2004 | 96.5 | 94.3 | 89.8 |
Kaplan-Meier survival curves for (a) cancer-specific survival of entire cohort, (b) cancer-specific survival by subgroups of different tumor stages, (c) cancer-specific survival by age subgroups, and (d) cancer-specific survival rate of patients by subgroups of different diagnosis year.
Table
Multivariate Analyses of Factors Associated with Cancer-Specific Mortality in Patients with Signet Ring Prostate Carcinoma.
Characteristics | Group | HR | 95% CI | |
---|---|---|---|---|
Age | 40–50 yrs | 1.00 | ||
51–60 yrs | 0.09 | 0.007–1.15 | 0.06 | |
61–70 yrs | 0.04 | 0.003–0.58 | 0.02 | |
0.02 | 0.001–0.37 | 0.01 | ||
Ethnicity | White | 1.00 | ||
Black | 2.32 | 0.23–23.5 | 0.47 | |
Others | 2.51 | 0.29–21.6 | 0.40 | |
SEER Stage | Local | 1.00 | ||
Distant | 10.9 | 1.44–82.09 | 0.02 | |
Unstaged | 5.23 | 0.70–39.3 | 0.11 | |
Marital status | Married | 1.00 | ||
No | 0.11 | 0.01–0.93 | 0.04 | |
Diagnosis year | 1980–1994 | 1.00 | ||
1995–2004 | 0.12 | 0.02–0.62 | 0.01 | |
Prostatectomy | No | 1.00 | ||
Yes | 0.57 | 0.07–4.40 | 0.59 | |
Radiation | No | 1.00 | ||
Yes | 0.28 | 0.03–2.52 | 0.25 |
HR: Hazard ratio; CI: Confidence interval.
Because of the rarity of SRPC, previously published information has been based on case series and single institutional experiences, which may not represent “real world” patients. Large, tertiary-care referral centers with mature local, regional, and national referral patterns may have a disproportionate number of advanced and recurrent tumors as well as a healthier population able to travel to these centers. This study takes advantage of the vast amount of data collected by the national SEER Program to examine the largest series of SRPC reported to date. We examine the incidence, natural history, predictors of utilization of prostatectomy, radiation therapy, and factors that affect the survival for SRPC by using the national population-based database. In this study, the total SRPC cases accounted for approximately 0.02% of primary prostate tumors included in the SEER database during study period. This incidence calculated in the SEER database is lower than reported in single institution studies [
The optimal treatment strategy for this subtype of prostate cancer is unknown since there is no clinical trial specifically designed for SRPC. In this study, we indentified significant age-and racial-related disparities as an important factor for selecting prostatectomy or radiation therapy, which is consistent with previous findings [
Consistent with single institution studies, the cancer-specific survival of SRPC is poor. In our study, the 3- and 5-year survival rates of SRPC were 89.6% and 83.8% (Table
Despite receiving more aggressive therapy, younger patients in this study had a poorer prognosis (Figure
Cancer incidence is known to be increased with age [
Currently, there is no literature addressing the impact of age on survival, specifically on SRPC. Our finding of age as an independent prognostic factor for this disease is interesting. The survival difference among different age groups might be explained by a difference in the biologic behavior of SRPC in the younger patients and elderly. Molecular research may provide additional insights into these questions. Similarly, breast cancer arising in young women is correlated with inferior survival and higher incidence of negative clinicopathologic features. A large-scale genomic analysis illustrates that breast cancer arising in young women is a unique biologic entity driven by unifying oncogenic signaling pathways [
Similar to the findings of increasing in 5-year survival in men with prostate cancer in post-PSA era, we also observed a significant improvement in the outcome of patients with SRPC during this period (Figure
Our findings should be interpreted with caution. First, this is a nonrandomized study; therefore, selection bias might have been present because patients undergoing surgery tend to be healthier. Although we adjusted for differences in demographic and tumor factors, residual confounding might still exist. Second, the pathological diagnoses in SEER were based on local pathologists' reports, and there was no central review of pathology reports. In addition, SEER data did not allow us to examine receipt of hormone or chemotherapy and patients’ comorbidities. However, the analysis reported here attempted to overcome this data limitation by measuring prostate cancer-specific survival, rather than overall survival. Finally, the sample size in our study may still not be large enough to fully describe the factors that affect the incidence, treatment choice, and survival of this rare prostate cancer subtype. Our findings may not necessarily be generalized to patients with prostate adenocarcinoma as a whole.
Strengths of this study include the population-based design, larger sample size, and inclusion of a broad spectrum of hospitals in the analysis. Having a larger sample size is of particular importance for analysis of rare subtype prostate cancer such as SRPC, where it is nearly impossible for a single institution to collect enough cases to facilitate a meaningful analysis regarding prognostic factors.
Based on the analysis of a population-based database, we report the results of the largest series of SRPC in the literature. Patients with SRPC have a worse survival compared to patients with other types of prostate cancer. Younger SRPC patients have significantly lower cancer-specific survival rate compared to their older counterparts. Further study to elucidate the mechanism of the differential biological behavior of SRPC in relation to host age is planned. The development of new strategies and molecular-based therapeutic approaches for younger patients with this aggressive tumor is urgently needed.