Hereditary prostate cancer: clinical characteristics and survival

PURPOSE: Hereditary prostate cancer accounts for 5% to 10% of all prostate cancer cases. We assessed clinical characteristics and survival in patients with hereditary prostate cancer MATERIALS AND METHODS: The study comprised 201 patients from 62 Swedish hereditary prostate cancer families and 402 controls with prostate cancer who were matched for age and calendar year at diagnosis, and the hospital where the diagnosis was made. Clinical data were obtained from the National Cancer Registry, Causes of Death Registry and medical records. RESULTS: Median age at the diagnosis of hereditary prostate cancer was 68 years, which was 6 years less than in patients with prostate cancer in the general population in Sweden. Distributions of tumor grade, symptoms at diagnosis and initial therapy were similar in hereditary prostate cancer cases and controls. More controls were classified with localized disease but it may have been due to methodological problems. Overall and cancer specific survival was similar in patients with hereditary prostate cancer and controls as well as in subgroup analyses including those with early onset and those diagnosed before 1990. Prostate cancer was the cause of death in 75% of patients with hereditary prostate cancer, in contrast to 55% with prostate cancer in the Swedish population. This difference was completely explained by the earlier age at the diagnosis of hereditary prostate cancer. CONCLUSIONS: Hereditary prostate cancer has an earlier onset than sporadic prostate cancer but this study did not indicate any other important difference in clinical characteristics or survival in patients with hereditary prostate cancer and those with sporadic prostate cancer. However, it cannot be excluded that individual hereditary prostate cancer genes may have specific biological characteristics.     

Targeted screening for prostate cancer in high risk families: early onset is a significant risk factor for disease in first degree relatives

PURPOSE: Targeted screening for prostate cancer in high risk families is generally suggested by ages 40 to 45 years in first degree relatives. We support this concept by reporting higher risk and earlier onset of the disease in these families. MATERIALS AND METHODS: We proposed serum prostate specific antigen (PSA) testing in 40 to 70-year-old first degree relatives of 435 patients with prostate cancer treated between July 1994 and June 1997. A previous systematic genealogical analysis allowed us to define the familial prostate cancer status of each patient as sporadic or familial. RESULTS: Of the 747 potential candidates 442 (59%) accepted into the study have been screened, including 240 who were 40 to 49 years old (mean age 44.8) and 202 who were 50 to 70 years old (mean age 57.4). Two of the 240 subjects (0.8%) had PSA greater than 4 ng./ml. in the 40 to 49-year-old group. Prostate biopsies were negative in 1 relative but diagnostic for prostate cancer in the other. In the 50 to 70-year-old group 25 of 202 subjects (12.4%) had a PSA of greater than 4 ng./ml. Prostate cancer was diagnosed in 9 individuals (4.5%), 9 had negative biopsy results, 1 died before biopsy and 6 refused biopsy. The proportion of relatives with PSA greater than 4 ng./ml. and prostate cancer detection was not different according to familial status (sporadic or familial) but it was significantly higher in first degree relatives with early onset prostate cancer in the family at ages younger than 65 years (p = 0.037 and 0.012, respectively). CONCLUSIONS: Our results emphasize the usefulness of PSA screening in high risk families, including those without obvious hereditary features. Furthermore, early onset prostate cancer is a significant risk factor for prostate cancer in first degree relatives.     

Impact of familial and hereditary prostate cancer on cancer specific survival after radical retropubic prostatectomy

PURPOSE: Men with a family history of prostate cancer are at higher risk for prostate cancer. There are conflicting data regarding the impact of hereditary forms of prostate cancer on long-term outcomes after radical prostatectomy. We examined the impact of familial and hereditary prostate cancer treatment in the prostate specific antigen era. MATERIALS AND METHODS: Patients who underwent radical prostatectomy for prostate cancer from 1987 to 1997 were surveyed (3,560 responders) to determine the family history of prostate cancer. Patients were categorized as having familial prostate cancer if they had at least 1 first-degree relative with prostate cancer. Hereditary prostate cancer was defined as nuclear families with 3 cases of prostate cancer, families with prostate cancer in each of 3 generations and families with 2 men diagnosed before age 55 years. Sporadic prostate cancer was defined as patients with no family history. Clinical and pathological features, and long-term outcome measures, including biochemical recurrence-free, systemic progression-free and cancer specific survival, were compared among patients with familial, hereditary and sporadic prostate cancer. RESULTS: A total of 865 and 133 patients were categorized as having familial prostate cancer and hereditary prostate cancer, respectively. Preoperatively prostate specific antigen was higher in patients with hereditary prostate cancer than in the other 2 groups (p = 0.04). Ten-year biochemical progression-free, systemic progression-free and cancer specific survival were equivalent. CONCLUSIONS: Except for preoperative prostate specific antigen, clinicopathological features and long-term oncological outcomes are equivalent after radical prostatectomy in patients with familial, hereditary and sporadic prostate cancer.     

Hereditary Non-medullary Thyroid Cancer

An estimated 5% of all non-medullary thyroid cancers are hereditary. If three or more first-degree relatives are affected, there is a greater than 94% chance that these cases are hereditary non-medullary thyroid cancer (HNMTC). Although, the susceptibility gene(s) for HNMTC has not been identified, there are enough epidemiologic studies and kindreds reported to suggest a hereditary predisposition to thyroid cancer. Until the susceptibility genes are identified, clinicians will have to rely on comprehensive history taking to identify at-risk families and clinically screen at-risk family members. When families are at risk for HNMTC, it is unclear whether neck examination and or neck ultrasound is most effective for screening. Hereditary non-medullary thyroid cancer is associated with more aggressive disease than sporadic HNMTC, especially in index cases, with higher rates of multicentric tumors, lymph node metastasis, and extrathyroidal invasion. Aggressive screening may benefit other members of the affected kindred because the outcome for the non-index cases is better. Although no studies have demonstrated any difference in mortality in patients with HNMTC versus sporadic disease, disease-free survival is shorter in HNMTC. Aggressive surgical and postoperative medical therapy is warranted in patients with HNMTC. It is likely that emerging molecular approaches may help identify the gene or genes involved in HNMTC which would have important clinical ramifications. Presented at the 42nd World Congress of Surgery of the International Society of Surgery and International Association of Endocrine Surgeons meeting, August 29th, 2007.     

Association between the clinical presentation and epidemiological features of familial prostate cancer in patients selected for radical prostatectomy

OBJECTIVE: We evaluated if epidemiological features of familial prostate cancer are associated with certain clinical or histopathological characteristics of the disease. METHODS: 463 German patients with familial prostate cancer who underwent radical prostatectomy were stratified according to several epidemiological criteria: (1). the apparent mode of disease transmission, (2). the average age of onset and (3). number of affected relatives/family, (4). whether or not they met the Johns Hopkins criteria of hereditary prostate cancer. The variables analysed included the Prostate Specific Antigen (PSA) and the digital rectal examination at diagnosis, histopathological characteristics of the prostatectomy specimen and relapse free 5-year survival rates. These characteristics were compared within the subsets of familial patients and compared to 492 control patients with sporadic prostate cancer. RESULTS: Age of onset was the only clinical parameter differentiating familial and sporadic prostate cancer. Otherwise there was no association between epidemiological features of familial predisposition and the clinical presentation or outcome of the disease. CONCLUSIONS: Familial and sporadic prostate cancer seem to be the same disease. Alternatively it may be concluded that the common epidemiological features of familial prostate cancer are not useful to tell tumours that are based on inherited susceptibility apart from those that are not. Whether hereditary prostate cancer is clinically distinct from sporadic forms cannot be determined before the underlying genetic alterations are identified.     

Prostate cancer and genetic susceptibility: a genome scan incorporating disease aggressiveness

BACKGROUND: Prostate cancer is a heterogeneous disease, both genetically and phenotypically. Linkage studies attempting to map genes for hereditary prostate cancer (HPC) have proved challenging, and one potential problem contributing to this challenge is the variability in disease phenotypes. METHODS: We collected clinical data on 784 affected men with prostate cancer from 248 HPC families for whom a genomic screen was performed. Disease characteristics (i.e., Gleason score, stage, prostate-specific antigen (PSA)) were used to classify affected men into categories of clinically insignificant, moderate, or aggressive prostate cancer. To potentially enrich for a genetic etiology, we restricted linkage analyses to only men with aggressive disease, although we used genotype information from all family members; linkage analyses used both dominant and recessive models. In addition, subset analyses considered age at diagnosis, number of affected men per family and other stratifications to try to increase genetic homogeneity. RESULTS: Several regions of interest (heterogeneity LOD score, HLOD>1.0) were identified in families (n=123) with >or=2 affecteds with aggressive prostate cancer. "Suggestive" linkage was observed at chromosome 22q11.1 (Dominant model HLOD=2.18) and the result was stronger (Dominant HLOD=2.75) in families with evidence of male-to-male transmission. A second region at 22q12.3-q13.1 was also highlighted (Recessive model HLOD=1.90) among men with aggressive disease, as was a region on chromosome 18. CONCLUSIONS: These analyses suggest that using clinically defined phenotypes may be a useful approach for simplifying the locus heterogeneity problems that confound the search for prostate cancer susceptibility genes.     

Evaluation of SRD5A2 sequence variants in susceptibility to hereditary and sporadic prostate cancer

BACKGROUND: The 5 alpha-reductase type II (SRD5A2) catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone (DHT), and is thus believed to be the key enzyme for the control of intracellular DHT level in the prostate. Several single nucleotide polymorphisms (SNPs) in the SRD5A2 gene have been found to alter enzymatic activities and were associated with prostate cancer risk or clinical features in several case-control studies. However, the role of SRD5A2 sequence variants in the susceptibility to hereditary prostate cancer (HPC) has not been evaluated to date. METHODS: Three SNPs in the SRD5A2 gene (A49T, V89L, and C682G) and two microsatellite markers near SRD5A2 were genotyped in 159 HPC families to assess their linkage to prostate cancer. In addition, the three SNPs were also genotyped in 245 sporadic cases and 222 unaffected controls to assess their association with hereditary and sporadic prostate cancer. RESULTS: Weak evidence for linkage in the SRD5A2 chromosomal region was observed in the 159 HPC families (HLOD = 0.87, P = 0.04). Stronger evidence for linkage was observed in Caucasian families (HLOD = 1.10, P = 0.02). When stratified by the SNP A49T, no significant evidence for linkage was observed in families with or without the "T" allele. Similarly, family-based association tests failed to observe significant over-transmission of any risk alleles of SNPs A49T, V89L, and C682G to affected offspring. Finally, no significant differences in the distributions of SNPs A49T, V89L, and C682G were found among the HPC probands, sporadic cases, and controls. CONCLUSIONS: Polymorphisms of SRD5A2 are unlikely to significantly increase susceptibility to hereditary or sporadic prostate cancer in the study populations.     

Psychological aspects of screening in families with hereditary prostate cancer

OBJECTIVE: Approximately 5-10% of prostate cancer cases are caused by dominantly inherited susceptibility to the disease. Although advances have been made in research concerning the genetic mechanisms of hereditary prostate cancer, little is known about the psychological consequences. The aim of this study was to assess possible negative psychological effects of screening for prostate cancer in a high-risk population. MATERIAL AND METHODS: This study was based on a previous study of risk perception, screening practice and interest in genetic testing among unaffected men in families with hereditary prostate cancer. The present study included 87 men from the previous study who were screened regularly for prostate cancer. Of these, 74 men agreed to receive two further questionnaires, both of which included the Hospital Anxiety and Depression Scale (HAD) and the Impact of Event Scale (IES), one of which was filled in on the day of the next screening visit and the other 4-6 weeks later. RESULTS: The response rate was 77% (57/74). There were no statistically significant differences in total or subscale HAD or IES scores between the two points of measurement. There was a trend towards slightly higher HAD scores on the day of the screening visit, but the difference was so small that we did not consider it clinically relevant. In an attempt to identify risk factors for a negative impact of screening several subgroup analyses were performed, but none of these subgroups had significantly higher scores on the day of the visit than afterwards. CONCLUSION: Most men with a high hereditary risk of developing prostate cancer do not experience severe psychological adverse effects resulting from attendance for screening.     

Analysis of the gene coding for the BRCA2-interacting protein PALB2 in hereditary prostate cancer

BACKGROUND: The genetic basis of susceptibility to prostate cancer (PRCA) remains elusive. Mutations in BRCA2 have been associated with increased prostate cancer risk and account for around 2% of young onset (<56 years) prostate cancer cases. PALB2 is a recently identified breast cancer susceptibility gene whose protein is closely associated with BRCA2 and is essential for BRCA2 anchorage to nuclear structures. This functional relationship made PALB2 a candidate PRCA susceptibility gene. METHODS: We sequenced PALB2 in probands from 95 PRCA families, 77 of which had two or more cases of early onset PRCA (age at diagnosis <55 years), and the remaining 18 had one case of early onset PRCA and five or more total cases of PRCA. RESULTS: Two previously unreported variants, K18R and V925L were identified, neither of which is in a known PALB2 functional domain and both of which are unlikely to be pathogenic. No truncating mutations were identified. CONCLUSIONS: These results indicate that deleterious PALB2 mutations are unlikely to play a significant role in hereditary prostate cancer.     

Association of hereditary prostate cancer gene polymorphic variants with sporadic aggressive prostate carcinoma

BACKGROUND: ELAC2, MSR1, and RNASEL are candidate genes for hereditary prostate carcinoma (HPC). While, studies have demonstrated that single nucleotide polymorphisms (SNPs) in these genes are associated with sporadic disease as well as HPC, these results are often not replicated in follow-up studies. Given that the majority of patients studied had localized disease and up to 50% of localized prostate cancer is clinically insignificant, the inability to replicate the initial findings may reflect that some subjects had indolent tumors. Herein, we examine patients with metastatic disease to determine if an association exists between HPC SNPs and unambiguously significant prostate cancer. METHODS: We examined polymorphisms within ELAC2 (S217L, A541T, E622V), MSR1 (P275A, R293X, aIVS5-59c), and RNASEL (E265X, R462Q, D541E) in 150 European-Americans with metastatic prostate cancer and 170 prostate cancer-free controls using pyrosequencing assays. RESULTS: Only ELAC2 217L (37% cases vs. 29% controls (P=0.034)) and RNASEL 541E (61% cases vs. 53% controls (P=0.045)) were over-represented. Analysis of genotypes revealed that presence of the leucine ELAC2 allele (OR 1.54: 95% CI=0.99-2.41, SS vs. SL, LL) and homozygosity for the glutamic acid RNASEL allele (OR 1.68: 95% CI=1.04-2.70, EE vs. DE, DD) were associated with increased risk. Patients with both genotypes were of particularly high-risk (OR 2.66: 95% CI=1.36-5.19). CONCLUSIONS: These results suggest that, in a European-American population, ELAC2 217L and RNASEL 541E are associated with metastatic sporadic disease. ELAC2 and RNASEL SNP analysis may prove useful in determining which patients are at risk for developing clinically significant prostate carcinoma.     

Clinical and histopathological characteristics of familial prostate cancer in Finland

Study Type – Aetiology (cohort) Level of Evidence 2b

OBJECTIVE

? To describe clinical and histopathological characteristics of Finnish familial prostate cancer (PCa) through a detailed analysis of cases in families.

PATIENTS AND METHODS

? In total, 202 Finnish families with 617 histopathologically confirmed PCa cases of confirmed genealogy were collected. ? Complete clinical data, including age and prostate‐specific antigen (PSA) at diagnosis, stage, grade and primary treatment, were gathered. The mean (range) number of affected men per family was 3 (2–8). ? All the available diagnostic biopsy samples (n= 323) were collected and regraded by the same uropathologist. ? A population‐based cohort of 3011 hospital district Pirkanmaa PCa patients was used as a control group.

RESULTS

? The mean (range) year of diagnosis of PCa was 1993 (1962–2006) and the mean (range) age at diagnosis was 68 (43–98 years). ? The median (range) primary PSA level was 12.0 (0.8–11 000) ng/mL. After regrading, the Gleason score was ≤6 in 38%, 7 in 37% and ≥8 in 25% of men. ? The subset of familial PCa men diagnosed after 1995 had higher PSA levels (P= 9.9 × 10^?6) and an earlier age of onset (P= 1.7 × 10^?6) than men in the control group, although there were no differences in cancer‐specific survival.

CONCLUSIONS

? We observed an earlier age of onset and higher PSA in familial PCa. ? However, differences between sporadic and familial or hereditary PCa cannot be truly solved until genetic testing of high‐risk genes in addition to family history is used to define PCa families. ? We also emphasize that, when histological samples are collected over a longer study period, reanalysis of the samples by the same experienced uropathologist should be considered. What’s known on the subject? and What does the study add? Previous hospital‐ or population‐based cross‐sectional studies comparing the clinical and histopathological features of hereditary, familial and sporadic PCa either reported weak trends or no differences in features measured except the age of onset. In present study we observed higher PSA and earlier age of onset in the subset of 257 familial PCa menin Finnish PCa families.     

Genome-wide screen for prostate cancer susceptibility genes in men with clinically significant disease

BACKGROUND: One of the difficulties confronting genetic studies of prostate cancer is the complex and heterogeneous etiology. Given the high population frequency of lesions meeting the histological definition of prostate cancer, a significant portion of men with a positive family history may be diagnosed due to increased surveillance and associated higher likelihood of biopsy. Over diagnosis decreases power to detect genes that increase susceptibility to a clinically significant prostate cancer. METHODS: We re-evaluated all 623 men with prostate cancer in our 188 hereditary prostate cancer families and identified a subset of 244 men with more aggressive disease based upon meeting at least one of the following clinical and/or pathologic criteria: tumor grade Gleason score > or = 7, tumor stage T2c or higher, pretreatment PSA > or = 20 ng/ml, rising PSA after treatment, evidence of metastasis, or death from prostate cancer. RESULTS: Genome-wide screens were re-performed by defining men as affected only if they met the criteria for clinically significant disease. The new analyses identified stronger evidence for linkage in Xq27-28 and 22q, as well as several novel loci, including 3p and 9p. CONCLUSIONS: Although, these results need to be confirmed in independent studies, our approach represents an important step to overcome the impact of over diagnosis in genetic studies of prostate cancer. Larger studies that incorporate this approach are needed.     

Links between genetic and environmental factors and prostate cancer risk.

BACKGROUND: Genetic polymorphisms and expression of steroid receptors may explain why some individuals are more at risk of developing prostate cancer. Some risk factors often discussed are androgen stimulation, and vitamin A and D deficiency. Long CAG-repeats in exon 1 of the androgen receptor (AR) gene on the X chromosome seem to have a protective role against androgen overstimulation. Likewise, long vitamin D receptor alleles in the poly-A tract may prevent vitamin D stimulation. METHODS: Blood samples from 59 Swedish patients with sporadic prostate cancers, 59 with hereditary prostate cancer, and 34 Japanese prostate cancer patients were compared with benign controls. Tissue specimens from 37 Swedish and 23 Japanese prostate cancer patients with matching blood samples were investigated by immunohistochemical techniques. RESULTS: The number of CAG-repeats was identical in sporadic and hereditary prostate cancer patients, but the repeats were significantly shorter than in benign controls. Benign Japanese controls were similar to Swedish controls, but Japanese prostate cancers had longer repeats than did controls. Both the vitamin D and A receptor staining was stronger in Japanese than in Swedish prostate cancer specimens. Prostate cancer occurs approximately 5 years later in Japanese compared with Swedish men. CONCLUSIONS: Varying lengths of CAG-repeats of the androgen receptor cannot fully explain racial differences in clinical prostate cancer incidence. A larger content of vitamin A and D receptors may be linked to a delayed onset of clinical prostate cancer in Japanese men.     

Allelic imbalance in hereditary and sporadic prostate cancer

BACKGROUND: In this study, we evaluate the pattern of allelic imbalance (AI) in both sporadic prostate cancer (SPC) and hereditary prostate cancer (HPC) at loci that frequently show allelic imbalance in sporadic prostate cancer, or are believed to have a putative role in the disease. METHODS: DNA obtained from 35 sporadic tumors and 46 hereditary tumors were tested for AI, by using a panel of 35 microsatellite markers. RESULTS: Chromosomal regions that display high frequencies of AI (>or=30%) in HPC include 1q, 5q, 7q, 8p, 13q, 16q, 17q, 18q, and 20q. In SPC, high frequencies of AI were found at 5q, 7q, 8p, 10q, 13q. Main differences (delta >or= 20%) in AI between HPC and SPC were at 1q, 10q, 17q, 18q, and 20q. CONCLUSION: AI at the prostate cancer susceptibility loci HPC1, PCaP, and HPC20 was seen more often in HPC compared with SPC. It appears that there are marked differences in the pattern of AI between sporadic and hereditary PCa.     

Ten years national research project "familial prostate cancer": problems in identifying risk families

Background

The German national research project??familial prostate cancer?? has been recruiting prostate cancer patients nationwide since 1999. In 2009, a comprehensive data analysis of the 25,065 families recruited was performed. Of these, 77.4% were identified as sporadic, 20.0% as familial and 2.6% as hereditary cases of prostate cancer. However, obtaining comprehensive, validated information about all relatives often fails.

Results

The high average age of the patients, the lower life expectancy in further generations and the low number of first-degree male relatives hampers the classification of sporadic, familial and hereditary cases. Consequently we describe here that in our database the identification of 100 hereditary cases requires a recruitment of more than 5,000 patients with their families. For 100 sporadic patients with 2 first-degree male relatives without a case history 1,250 patients are needed.     

Assoziation von familiärem Status mit Histologie und klinischem Verlauf beim frühen Prostatakarzinom

BACKGROUND: In a large number of studies a positive family history is documented as one of the main risk factors for the development of prostate cancer. In a US population an association between early-onset prostate cancer among familial patients and a more differentiated tumour was shown. The aim of this study was to compare clinical parameters between sporadic and familial or hereditary patients with an age at diagnosis < or =55 years. MATERIAL AND METHODS: The clinical data of prostate cancer patients with an age at diagnosis < or =55 years and who were recruited between July 1999 and the end of June 2004 to the database "familial prostate cancer in Germany" were analysed. The following data were documented for all patients: PSA at diagnosis, histopathological stage, grading, Gleason score and progression-free survival. RESULTS: The clinical data of 685 patients could be completed: 222 (32.4%) had one first-degree relative with prostate cancer, 48 of whom (7.0%) were hereditary; 463 (67.6%) were sporadic. The median age at diagnosis in the hereditary patients was 51.6 (41-55) years, in the familial patients 51.1 (35-55) years and in the sporadic patients 52.0 (38-55) years. The median follow-up was 24 months in hereditary, 36 months in familial and 35 months in sporadic patients. An initial curative therapy with radical prostatectomy or radiotherapy/brachytherapy was planned in 657/685 (95.9%) of the patients. There were no clear differences regarding PSA at diagnosis, the postoperative parameters (organ-confined disease, lymph node involvement, Gleason score, grading) and the progression-free survival in sporadic and familial or hereditary patients. CONCLUSIONS: Patients with an age at diagnosis < or =55 years have a positive family history more often than all prostate cancer patients in Germany. No association could be shown between pathohistological stage or clinical course and a positive family history in patients with an age at diagnosis < or =55 years.     

Preventing prostate carcinoma in men with familial disposition

A family history is one of the strongest risk factors for prostate cancer (PC). We evaluated the detection rate of PC in relatives of 119 German PC families that took part in ongoing linkage analyses. Brothers of patients with sporadic prostate cancer aged < 55 years at onset were included as well. Responses were received from 120/196 (61.2%) individuals of the familial and 67/120 (55.8%) of the sporadic group. Findings (DRE, TRUS, PSA) were more often suspicious for carcinoma in the PC families. Prostate cancer was diagnosed in 6 (5.0%) and 2 (2.99%) participants of the familial and the sporadic group, respectively. These detection rates tended to be higher than that of an age-matched subgroup of an unselected population in other European screening studies. The most important risk factor for the diagnosis of PC was a low average age at onset within the family. These data imply that prostate cancer screening in the high-risk group of men with familial predisposition cannot be assessed by population-based studies and should be evaluated separately.     

Challenges in Interpreting Germline Mutations in BARD1 and ATM in Breast and Ovarian Cancer Patients

Next‐generation sequencing promotes identification of mutations in non‐BRCA1/2 genes in hereditary cancer families. The contribution of mutations in moderate penetrance genes to hereditary cancer risk is not well established. Here, we report a family with early onset breast and fallopian tube cancer that was identified as carrying germline mutations in BARD1 and ATM genes. Loss of heterozygosity studies suggest a causative role of the BARD1 mutation in the development of primary peritoneal cancer, but fail to confirm an association between germline ATM mutations and breast cancer development in this family. Complexities in interpreting implications of mutations in moderate‐risk cancer susceptibility genes are discussed.     

Familial versus sporadic prostate cancer in the German population. Clinical and pathological characteristics in patients after radical prostatectomy

Family history is one of the strongest epidemiological risk factors for the development of prostate cancer. The impact on the clinical presentation and prognosis, however, is controversial. In the present study, we analyzed 464 familial and 492 sporadic prostate cancer patients following radical prostatectomy. The average age at onset was 62.1 years in the familial group and 64.2 years in the sporadic controls (p<0.001). The screening attitude, DRE findings and the PSA values at diagnosis the pT- and pN-stages, and the tumor grade did not differ between both groups. With a median follow-up of 3.3 years, the 5- and 10-year progression-free survival rates were 76.2% and 56.5% in familial and 70.8% and 55.5% in sporadic patients, respectively (n.s.). A multiple logistic regression analysis revealed that family history did not have an influence on disease recurrence. In our population there was no association between a familial predisposition and clinical features or clinical course of the disease. Whether hereditary prostate cancer is distinct from sporadic forms cannot be determined before the underlying genetic alterations are identified.