RESUMEN
BACKGROUND: To evaluate the relationship between PSA testing history and high-risk disease among older men diagnosed with prostate cancer. METHODS: Records from 1993 to 2014 were reviewed for men who underwent radiotherapy for prostate cancer at age 75 years or older. Patients were classified into one of four groups based on PSA-testing history: (1) no PSA testing; (2) incomplete/ineffective PSA testing; (3) PSA testing; or (4) cannot be determined. Outcomes of interest were National Comprehensive Cancer Network (NCCN) risk group (that is, low, intermediate or high risk) and biopsy grade at diagnosis. Multivariable logistic regression was used to determine the association between PSA testing history and high-risk cancer. RESULTS: PSA-testing history was available in 274 (94.5%) of 290 subjects meeting study criteria. In total, 148 men (54.0%) underwent PSA testing with follow-up biopsy, 72 (26.3%) underwent PSA testing without appropriate follow-up, and 54 men (19.7%) did not undergo PSA testing. Patients who underwent PSA testing were significantly less likely to be diagnosed with NCCN high-risk cancer (23.0% vs 51.6%, P<0.001). On multivariable analysis, men with no/incomplete PSA testing had more than three-fold increased odds of high-risk disease at diagnosis (odds ratio 3.39, 95% confidence interval 1.96-5.87, P<0.001) as compared to the tested population. CONCLUSIONS: Older men who underwent no PSA testing or incomplete testing were significantly more likely to be diagnosed with high-risk prostate cancer than those who were previously screened. It is reasonable to consider screening in healthy older men likely to benefit from early detection and treatment.
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Detección Precoz del Cáncer , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Biopsia , Humanos , Modelos Logísticos , Masculino , Próstata/patología , Neoplasias de la Próstata/patología , Medición de Riesgo , Factores de RiesgoRESUMEN
African American men have the highest incidence of prostate cancer in the world. Despite this statistic, linkage studies designed to localise prostate cancer susceptibility alleles have included primarily men of Caucasian descent. In this report, we performed a linkage analysis using 33 African American prostate cancer families from two independent research groups. In total, 126 individuals (including 89 men with prostate cancer) were genotyped using markers that map to five prostate cancer susceptibility loci, namely HPC1 at 1q24-25, PCAP at 1q42.2-43, CAPB at 1p36, HPC20 on chromosome 20, and HPCX at Xq27-28. Multipoint mode-of-inheritance-free linkage analyses were performed using the GENEHUNTER software. Some evidence of prostate cancer was detected to HPC1 using all families with a maximum NPL Z score of 1.12 near marker D1S413 (P=0.13). Increased evidence of linkage was observed in the 24 families with prostate cancer diagnosis prior to age 65 years and in the 20 families with male-to-male transmission. Some evidence of prostate cancer linkage was also detected at markers mapping to PCAP, HPC20, and HPCX. Continued collection and analysis of African American prostate cancer families will lead to an improved understanding of inherited susceptibility in this high-risk group.
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Negro o Afroamericano/genética , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 20 , Cromosomas Humanos X , Ligamiento Genético , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/genética , Anciano , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Linaje , Reacción en Cadena de la Polimerasa , Programas InformáticosRESUMEN
CYP1B1 has been evaluated as a candidate gene for various cancers because of its function in activating environmental procarcinogens and catalysing the conversion of oestrogens to genotoxic catechol oestrogens. To test the hypothesis that genetic polymorphisms in the CYP1B1 gene may associate with the risk for prostate cancer (CaP), we compared the allele, genotype, and haplotype frequencies of 13 single nucleotide polymorphisms (SNPs) of CYP1B1 among 159 hereditary prostate cancer (HPC) probands, 245 sporadic CaP cases, and 222 unaffected men. When each of the SNPs was analysed separately, marginally significant differences were observed for allele frequencies between sporadic cases and controls for three consecutive SNPs (-1001C/T, -263G/A, and -13C/T, P=0.04-0.07). Similarly, marginally significant differences between sporadic cases and controls in the frequency of variant allele carriers were observed for five consecutive SNPs (-1001C/T, -263G/A, -13C/T, +142C/G, and +355G/T, P=0.02-0.08). Interestingly, when the combination of these five SNPs was analysed using a haplotype approach, a larger difference was found (P=0.009). One frequent haplotype (C-G-C-C-G of -1001C/T, -263G/A, -13C/T, +142C/G, and +355G/T) was associated with an increased risk for CaP, while the other frequent haplotype (T-A-T-G-T) was associated with a decreased risk for CaP. These findings suggest that genetic polymorphisms in CYP1B1 may modify the risk for CaP.
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Hidrocarburo de Aril Hidroxilasas/genética , Predisposición Genética a la Enfermedad , Polimorfismo Genético , Neoplasias de la Próstata/genética , Hidrocarburo de Aril Hidroxilasas/farmacología , Citocromo P-450 CYP1B1 , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Factores de RiesgoRESUMEN
The 8p22 through p23 region has been identified as a potential site for genes associated with prostate cancer. The gene LZTS1 has been mapped to the 8p22 through p23 region and identified as a potential tumor suppressor based on loss of heterozygosity studies using primary esophageal tumors. Sequence analysis of mRNA from various tumors has revealed multiple mutations and aberrant mRNA transcripts. The most recent report associates LZTS1 function with stabilization of p34(cdc2) during the late S-G2/M stage of mitosis, affecting normal cell growth. In this study, a detailed DNA sequence analysis of LZTS1 was performed in a screening panel consisting of sporadic and hereditary prostate cancer (HPC) cases and unaffected controls. Twenty-four SNP, 15 of which were novel, were identified in germline DNA. Four coding SNP were identified. Eleven informative SNP were genotyped in 159 HPC probands, 245 sporadic prostate cancer cases, and 222 unaffected controls. Four of these SNP were statistically significant for association with prostate cancer (P < or = 0.04). These results add evidence supporting a role of LZTS1 in prostate cancer risk.
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Cromosomas Humanos Par 8 , Proteínas de Unión al ADN/genética , Genes Supresores de Tumor , Variación Genética , Mutación de Línea Germinal , Neoplasias de la Próstata/genética , Proteínas Supresoras de Tumor , Secuencia de Bases , Mapeo Cromosómico , Cartilla de ADN , Humanos , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Neoplasias de la Próstata/epidemiología , Factores de RiesgoRESUMEN
OBJECTIVES: We previously presented nomograms combining preoperative serum prostate-specific antigen (PSA), clinical (TNM) stage, and biopsy Gleason score to provide the likelihood of various final pathologic stages at radical retropubic prostatectomy. The data for the original nomograms were collected from men treated between 1982 and 1996. During the past 10 years, the stage at presentation has shifted, with more men presenting with Stage T1c, Gleason score 5 to 6, and serum PSA levels less than 10.0 ng/mL. In this work, we update the "Partin Tables" with a more contemporary cohort of men treated since 1994 and with revised PSA and Gleason categories. METHODS: Multinomial log-linear regression analysis was used to estimate the likelihood of organ-confined disease, extraprostatic extension, seminal vesicle or lymph nodal status from the preoperative PSA stratified as 0 to 2.5, 2.6 to 4.0, 4.1 to 6.0, 6.1 to 10.0, and greater than 10 ng/mL, clinical (AJCC-TNM, 1992) stage (T1c, T2a, T2b, or T2c), and biopsy Gleason score stratified as 2 to 4, 5 to 6, 3 + 4 = 7, 4 + 3 = 7, or 8 to 10 among 5079 men treated with prostatectomy (without neoadjuvant therapy) between 1994 and 2000 at Johns Hopkins Hospital. The average age was 58 years. RESULTS: In this cohort, more than 60% had T1c, more than 75% had Gleason score of 6, more than 70% had PSA greater than 2.5 and less than 10.0 ng/mL, and more than 60% had organ-confined disease. Nomograms of the robust estimated likelihoods and 95% confidence intervals were developed from 1000 bootstrap analyses. The probability of organ-confined disease improved across the groups, and further stratification of the Gleason score and PSA level allowed better differentiation of individual patients. CONCLUSIONS: These updated "Partin Tables" were generated to reflect the trends in presentation and pathologic stage for men newly diagnosed with clinically localized prostate cancer at our institution. Clinicians can use these nomograms to counsel individual patients and help them make important decisions regarding their disease.
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Estadificación de Neoplasias/métodos , Antígeno Prostático Específico/sangre , Próstata/patología , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Adulto , Anciano , Intervalos de Confianza , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/tendencias , Palpación , Probabilidad , Neoplasias de la Próstata/mortalidad , Análisis de RegresiónRESUMEN
OBJECTIVES: To evaluate the influence of isolated, histologically identified capsular incision (CI) (exposure of benign or malignant glands to the inked surgical margin in the setting of organ-confined disease) on disease progression after anatomic radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. METHODS: Between March 1993 and September 1999, 4747 men underwent RRP at the Johns Hopkins Hospital; 107 men (2.3%) were diagnosed with CI in otherwise organ-confined disease; 92 (86%) had at least 6 months (mean 30) of follow-up. We matched these CI cases (based on surgeon, age, clinical stage, final pathologic Gleason grade, and preoperative serum prostate-specific antigen level) one-for-one with controls in three additional pathologically defined groups and compared the freedom from disease progression (prostate-specific antigen level greater than 0.2 ng/mL and/or local palpable recurrence) after RRP. RESULTS: The actuarial 3-year likelihood of freedom from disease progression was 87.8% for the CI group, 96.4% for men with organ-confined disease (P = 0.10), 91.3% for men with extraprostatic extension and negative surgical margins (P = 0.99), and 73.9% for men with positive surgical margins resulting from extraprostatic extension (P <0.01). No statistically significant difference was found in the actuarial likelihood of freedom from disease progression between men with CI into benign glands (n = 22) and men with CI into tumor (n = 70) (P = 0.93). CONCLUSIONS: No statistically significant difference was found in the likelihood of early recurrence between patients with isolated CI and other specimen-confined disease. Patients with isolated CI have a significantly lower likelihood of early recurrence than patients with positive surgical margins due to extraprostatic extension, regardless of whether the CI is into benign glands or tumor. Long-term follow-up is necessary to confirm these findings.
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Próstata/cirugía , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Adulto , Anciano , Estudios de Casos y Controles , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Pronóstico , Antígeno Prostático Específico/sangre , Prostatectomía/mortalidad , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patologíaRESUMEN
In a large series of 2404 men with a mean follow-up of 6.3 plus or minus 4.2 years (range, 1-17) after anatomic RRP for clinically localized prostate cancer, 412 men (17%) have recurred. A detectable PSA was the only evidence of recurrence in 9.7%, whereas 1.7% and 5.8% had local recurrence and distant metastasis, respectively. The overall actuarial 5-, 10-, and 15-year recurrence-free survival rates for these men were 84%, 74%, and 66%, respectively. As demonstrated in the authors' previous reports, the actuarial likelihood of a postoperative recurrence increased with advancing clinical stage, Gleason-score, preoperative PSA level, and pathologic stage. Subdivision of men with Gleason 7 tumors resulted in better stratification. There was a similar actuarial likelihood of postoperative recurrence for men with Gleason 4 + 3 and Gleason score 8 to 10 disease. The actuarial rate of recurrence of tumor for men with Gleason 3 + 4 disease was statistically different from the rate for men with Gleason score 6 or Gleason 4 + 3 disease. The overall actuarial metastasis-free survival rates at 5, 10, and 15 years were 96%, 90%, and 82%, respectively. The overall actuarial cancer-specific survival rates at 5, 10, and 15 years were 99%, 96%, and 90%, respectively. This study provides long-term outcome of patients with clinically localized cancer who underwent RRP between 1982 and 1999. Recognizing that this long-term study includes many patients with more advanced disease diagnosed before the PSA era, caution must be exercised in comparing these results with the outcomes for cohorts of patients treated since 1989. Anatomic RRP is an effective way to manage clinically localized prostate cancer. Excellent long-term results can be obtained with RRP for early stage disease. The proportion of men with early stage prostate cancer will continue to increase with wide use of serum PSA testing and digital rectal examination.
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Adenocarcinoma/cirugía , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Adenocarcinoma/sangre , Adenocarcinoma/patología , Adulto , Anciano , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Factores de TiempoRESUMEN
Androgens are essential for prostate development, growth and maintenance and the association between androgen levels and prostate cancer is well established. Since the CYP17 gene encodes the enzyme cytochrome P450c17alpha, which mediates 17alpha-hydroxylase and 17,20-lyase activities in the androgen biosynthesis pathway, sequence variations in the gene and association with increased risk to prostate cancer has been studied. In particular, several groups have studied the association between a polymorphism in the 5' promoter region and prostate cancer using a population-based association approach. However, the results from these studies were inconclusive. To further study this polymorphism and its possible role in hereditary prostate cancer (HPC), we performed a genetic linkage analysis and family-based association analysis in 159 families, each of which contains at least 3 first-degree relatives with prostate cancer. In addition, we performed a population-based association analysis to compare the risk of this polymorphism to hereditary and sporadic prostate cancer in 159 HPC probands, 249 sporadic prostate cancer patients and 211 unaffected control subjects. Evidence for linkage at the CYP17 gene region was found in the total 159 HPC families (LOD = 1.3, p = 0.01, at marker D10S222). However, family-based association tests did not provide evidence for overtransmission of either allele of the CYP17 polymorphism to affected individuals in the HPC families. The allele and genotype frequencies of the polymorphism were not statistically different among the HPC probands, sporadic cases and unaffected control subjects. In conclusion, our results suggest that the CYP17 gene or other genes in the region may increase the susceptibility to prostate cancer in men; however, the polymorphism in the 5' promoter region has a minor role if any in increasing prostate cancer susceptibility in our study sample.
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Ligamiento Genético , Neoplasias de la Próstata/genética , Esteroide 17-alfa-Hidroxilasa/genética , Adulto , Anciano , Alelos , Salud de la Familia , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo Genético , Regiones Promotoras GenéticasRESUMEN
PURPOSE: We assess whether the Gleason grade changes in men followed expectantly with clinical stage T1c prostate cancer. MATERIAL AND METHODS: We studied 70 men with stage T1c prostate cancer who underwent watchful waiting with repeat needle biopsy sampling to assess for progression. After the initial cancer diagnosis all men had at least 1 other biopsy demonstrating cancer. RESULTS: Of 70 cases 9 (12.9%) showed a significant change in grade from Gleason scores 6 or less to 7 or greater. The average followup of those patients without a change in grade was 22 months and greater than those with a change in grade. There was no difference between the groups with and without changes in grade in regard to initial prostate specific antigen (PSA), percent-free PSA, or PSA density or velocity. Of 9 cases there were 5 (56%) and 8 (89%) with grade change that occurred at 12 and 15 months or less after initial biopsy, respectively. In contrast, only 1 of 24 (4%) patients in whom last re-biopsy was performed 24 months or greater after the initial cancer diagnosis had a change in grade. Of the 21 men who underwent radical prostatectomy 5 (24%) had worsening of grade on the radical prostatectomy specimen compared to biopsy, with a mean interval of 18 months between the initial cancer diagnosis and prostatectomy. This prevalence of grade change is less than in our population that underwent prostatectomy within 1 to 3 months after biopsy. CONCLUSIONS: Because most grade changes occurred relatively soon after biopsy, it implies that tumor grade did not evolve but rather the higher grade component was not initially sampled. During a 1 1/2 to 2-year period after biopsy there is no evidence that prostate cancer grade worsens significantly. Men with prostate cancer need not feel concerned about waiting several months before undergoing surgery after biopsy. Furthermore, men undergoing watchful waiting can be reassured that there is little evidence that prostate cancer grade worsens during the short term.
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Adenocarcinoma/patología , Neoplasias de la Próstata/patología , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estadificación de NeoplasiasRESUMEN
Multiple lines of evidence have implicated the short arm of chromosome 8 as harboring genes important in prostate carcinogenesis. Although most of this evidence comes from the identification of frequent somatic alterations of 8p loci in prostate cancer cells (e.g., loss of heterozygosity), studies have also suggested a role for 8p genes in mediation of inherited susceptibility to prostate cancer. To further examine this latter possibility, we performed linkage analyses, in 159 pedigrees affected by hereditary prostate cancer (HPC), using 24 markers on the short arm of chromosome 8. In the complete set of families, evidence for prostate cancer linkage was found at 8p22-23, with a peak HLOD of 1.84 (P=.004), and an estimate of the proportion of families linked (alpha) of 0.14, at D8S1130. In the 79 families with average age at diagnosis >65 years, an allele-sharing LOD score of 2.64 (P=.0005) was observed, and six markers spanning a distance of 10 cM had LOD scores >2.0. Interestingly, the small number of Ashkenazi Jewish pedigrees (n=11) analyzed in this study contributed disproportionately to this linkage. Mutation screening in HPC probands and association analyses in case subjects (a group that includes HPC probands and unrelated case subjects) and unaffected control subjects were carried out for the putative prostate cancer-susceptibility gene, PG1, previously localized to the 8p22-23 region. No statistical differences in the allele, genotype, or haplotype frequencies of the SNPs or other sequence variants in the PG1 gene were observed between case and control subjects. However, case subjects demonstrated a trend toward higher homozygous rates of less-frequent alleles in all three PG1 SNPs, and overtransmission of a PG1 variant to case subjects was observed. In summary, these results provide evidence for the existence of a prostate cancer-susceptibility gene at 8p22-23. Evaluation of the PG1 gene and other candidate genes in this area appears warranted.
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Mapeo Cromosómico , Cromosomas Humanos Par 8/genética , Ligamiento Genético/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias de la Próstata/genética , Edad de Inicio , Alelos , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Judíos/genética , Escala de Lod , Masculino , Repeticiones de Microsatélite/genética , Datos de Secuencia Molecular , Mutación/genética , Oportunidad Relativa , Linaje , Polimorfismo de Nucleótido Simple/genética , Polimorfismo Conformacional Retorcido-Simple , Neoplasias de la Próstata/epidemiología , Grupos Raciales/genéticaRESUMEN
PURPOSE: We retrospectively reviewed a large series of men with clinically localized prostate cancer who underwent surgery to define the extent of stage migration and its influence on biochemical recurrence in 3 different eras of prostate cancer management. MATERIALS AND METHODS: A total of 2,370 men were treated with radical prostatectomy from 1982 to 1998. We analyzed the freedom from biochemical (prostate specific antigen) progression after radical prostatectomy. We compared the distribution of pathological stage by the year of surgery. We then compared the biochemical recurrence-free survival rate according to the different eras that reflect a change in prostate cancer management. RESULTS: There was a significant downward stage migration of prostate cancer and an increasing proportion of men who presented with organ confined disease in recent years. The actuarial biochemical recurrence-free rate was significantly different for patients who underwent surgery between 1982 and 1988, compared with those between 1989 and 1998 (p <0.001). These changes may have reflected the benefits of early detection with prostate specific antigen and digital rectal examination, better preoperative selection of patients for surgery as well as the effect of lead time. CONCLUSIONS: Widespread early detection programs for prostate cancer resulted in downward stage migration in men presenting with prostate cancer at our institution during the last 18 years. Also, we have demonstrated a biochemical recurrence-free survival advantage, probably secondary to an improved therapeutic outcome as well as lead time bias, in men who underwent surgery between 1989 and 1998, compared with those between 1982 and 1988. When trying to compare the efficacy of different treatment modalities for prostate cancer, the era in which patients underwent therapy is an important factor to be considered.
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Prostatectomía , Neoplasias de la Próstata/cirugía , Adulto , Anciano , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/análisis , Estudios RetrospectivosRESUMEN
PURPOSE: We present a structured debate supporting the premise that immediate hormonal intervention has not been conclusively shown to provide a survival advantage in the management of advanced prostate cancer. MATERIALS AND METHODS: The literature emphasizing randomized trials was reviewed. Recommendations are based solely on a demonstrated advantage in survival. RESULTS: In patients with stage Tx Nx Mo or MI disease who did not receive other primary therapy there is no demonstrated survival advantage to immediate hormonal therapy. In men with positive lymph nodes who underwent radical prostatectomy a relatively small study showed a survival advantage in favor of immediate hormonal treatment compared to deferred treatment. This study did not reach the projected accrual of 240 patients and results have not been supported by other trials. In men with stages T2-4 Nx Mx disease who underwent primary treatment with radiotherapy a survival advantage for early hormonal therapy is primarily limited to high risk subgroups. In patients with biochemical relapse following primary treatment there are no trials. CONCLUSIONS: Because hormonal therapy is associated with the development of irreversible resistance in virtually all patients, it does not cure, there is usually a long interval from first prostate specific antigen elevation to the development of metastatic disease, and hormonal therapy has profound side effects and is expensive, delayed treatment is recommended in men with biochemical relapse following surgery or radiotherapy. Patients should be strongly encouraged to enter clinical trials to answer this question.
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Antineoplásicos Hormonales/administración & dosificación , Neoplasias de la Próstata/terapia , Antineoplásicos Hormonales/efectos adversos , Ensayos Clínicos como Asunto , Humanos , Metástasis Linfática , Masculino , Estadificación de Neoplasias , Prostatectomía , Neoplasias de la Próstata/mortalidadRESUMEN
Prostate cancer is the most common malignancy diagnosed in men in the US. Genetic susceptibility to prostate cancer has been well documented. A region at chromosome 20q13 (HPC20) has been reported to be linked to a prostate cancer susceptibility gene. To confirm this finding, we genotyped 16 markers spanning approximately 95 cM on chromosome 20 in 159 hereditary prostate cancer (HPC) families. Positive (but not statistically significant) linkage scores were observed from 20pter to 20q11, with the highest non-parametric linkage (NPL) score for the complete dataset of 1.02 (P=0.15) being observed at D20S195 at 20q11. Evidence for linkage from parametric analyses with a dominant or a recessive model was weak. Interestingly, consistent with the original findings of linkage to 20 g higher linkage scores were observed in the subsets of families with a later age at diagnosis (> or =65 years; n=80, NPL=1.94, P=0.029 at D20S186), fewer than five affected family members (n=69, NPL=1.74, P=0.037 at D20S889), or without male-to-male disease transmission (n=60, NPL=1.01, P=0.15 at D20S117). The region with positive linkage scores spanned approximately 60 cM from 20pter to 20q11 in these subsets of families. Our results are consistent with a prostate cancer susceptibility locus on chromosome 20.
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Cromosomas Humanos Par 20/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias de la Próstata/genética , Anciano , Mapeo Cromosómico , Genes Dominantes , Genes Recesivos , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Modelos Genéticos , Población Blanca/genéticaAsunto(s)
Neoplasias de la Próstata/terapia , Anciano , Humanos , Masculino , Persona de Mediana EdadAsunto(s)
Erección Peniana , Pene/inervación , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Humanos , Masculino , Invasividad Neoplásica , Pene/irrigación sanguínea , Prostatectomía/efectos adversos , Neoplasias de la Próstata/patología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la FunciónRESUMEN
OBJECTIVES: To develop a model that will identify a contemporary cohort of patients at high risk of early prostate cancer recurrence (greater than 50% at 36 months) after radical retropubic prostatectomy for clinically localized disease. Data from this model will provide important information for patient selection and the design of prospective randomized trials of adjuvant therapies. METHODS: Proportional hazards regression analysis was applied to two patient cohorts to develop and cross-validate a multifactorial predictive model to identify men with the highest risk of early prostate cancer recurrence. The model and validation cohorts contained 904 and 901 men, respectively, who underwent radical retropubic prostatectomy at Johns Hopkins Hospital. This model was then externally validated using a cohort of patients from the Mayo Clinic. RESULTS: A model for weighted risk of recurrence was developed: R(W)'=lymph node involvement (0/1)x1.43+surgical margin status (0/1)x1.15+modified Gleason score (0 to 4)x0.71+seminal vesicle involvement (0/1)x0.51. Men with an R(W)' greater than 2.84 (9%) demonstrated a 50% biochemical recurrence rate (prostrate-specific antigen level greater than 0.2 ng/mL) at 3 years and thus were placed in the high-risk group. Kaplan-Meier analyses of biochemical recurrence-free survival demonstrated rapid deviation of the curves based on the R(W)'. This model was cross-validated in the second group of patients and performed with similar results. Furthermore, similar trends were apparent when the model was externally validated on patients treated at the Mayo Clinic. CONCLUSIONS: We have developed a multivariate Cox proportional hazards model that successfully stratifies patients on the basis of their risk of early prostate cancer recurrence.
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Recurrencia Local de Neoplasia/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Adulto , Anciano , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Palpación , Modelos de Riesgos Proporcionales , Prostatectomía/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Análisis de Regresión , Factores de TiempoRESUMEN
OBJECTIVES: To determine whether needle biopsy of the posterolateral aspects of the prostate aids in prostate cancer detection. In the routine sextant biopsy strategy, the posterolateral aspects of the prostate are not sampled. METHODS: Using an 18-gauge biopsy gun, we performed sextant biopsies and an additional nine needle biopsies in the pathology laboratory on 150 radical prostatectomy specimens performed for Stage T1c prostate cancer. The additional nine biopsies consisted of three midline biopsies and six (three each from the left and right) posterolaterally aimed biopsies from the apex, mid, and base regions of the gland. Significant tumors were defined as those greater than 0.5 cm3, or with a Gleason score of 7 or greater, or non-organ confined. RESULTS: Of the 123 cases with cancer on repeated biopsy, in only 3 (2.4%) was the only cancer found in the midline biopsies. For the following analysis, we analyzed the data as if we had not done the midline biopsies. If one had performed only the routine sextant needle biopsies, in 31 (25.2%) of the 123 cases, tumor would have been missed; 20 of these tumors were significant, including 5 with extraprostatic extension. If one had performed only the more posterolateral six biopsies, in 15 cases (12.2%), tumor would have been missed; 5 of these tumors were significant, all of which were organ confined. CONCLUSIONS: Adding routine midline biopsies does not appreciably increase the detection of cancer. If one were to only perform six needle biopsies of the prostate, these biopsies should be aimed more toward the posterolateral aspect of the gland. Maximum cancer detection results from combining both routine sextant and posterolateral needle biopsies.
Asunto(s)
Biopsia con Aguja/métodos , Próstata/patología , Neoplasias de la Próstata/patología , Humanos , Masculino , ProstatectomíaRESUMEN
Three prostate cancer susceptibility genes have been reported to be linked to different regions on chromosome 1: HPC1 at 1q24-25, PCAP at 1q42-43, and CAPB at 1p36. Replication studies analyzing each of these regions have yielded inconsistent results. To evaluate linkage across this chromosome systematically, we performed multipoint linkage analyses with 50 microsatellite markers spanning chromosome 1 in 159 hereditary prostate cancer families (HPC), including 79 families analyzed in the original report describing HPC1 linkage. The highest lod scores for the complete dataset of 159 families were observed at 1q24-25 at which the parametric lod score assuming heterogeneity (hlod) was 2.54 (P=0.0006) with an allele sharing lod of 2.34 (P=0.001) at marker D1S413, although only weak evidence was observed in the 80 families not previously analyzed for this region (hlod=0.44, P=0.14, and allele sharing lod=0.67, P=0.08). In the complete data set, the evidence for linkage across this region was very broad, with allele sharing lod scores greater than 0.5 extending approximately 100 cM from 1p13 to 1q32, possibly indicating the presence of multiple susceptibility genes. Elsewhere on chromosome 1, some evidence of linkage was observed at 1q42-43, with a peak allele sharing lod of 0.56 (P=0.11) and hlod of 0.24 (P=0.25) at D1S235. For analysis of the CAPB locus at 1p36, we focused on six HPC families in our collection with a history of primary brain cancer; four of these families had positive linkage results at 1p36, with a peak allele sharing lod of 0.61 (P=0.09) and hlod of 0.39 (P=0.16) at D1S407 in all six families. These results are consistent with the heterogeneous nature of hereditary prostate cancer, and the existence of multiple loci on chromosome 1 for this disease.