RESUMEN
Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.
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Genómica , Neoplasias de la Próstata/clasificación , Anciano , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , RiesgoRESUMEN
The goal of this study was to determine whether inactivating specific cytokines in seminal plasma improves sperm motility in men affected by spinal cord injury (SCI). For this purpose, we used monoclonal antibodies to interleukin 6 (IL6), interleukin 1 beta (IL1-beta), and tumor necrosis factor alpha (TNF-alpha), all 3 cytokines having been previously detected at high concentrations in the seminal plasma of patients with SCI. In a group of 17 SCI men with low sperm motility (mean +/- SE, 20.1% +/- 3.1%), treatment with the 3 monoclonal antibodies at the median neutralization dose concentrations for 1.0 to 1.5 hours improved sperm motility in all cases. Effectiveness was higher in those specimens with a pretreatment sperm motility between 11% and 30% (from 19.3% +/- 1.4% to 41.9% +/- 4.9%, P < .0002), suggesting that pretreatment sperm motility might represent an indicator of cell damage and, therefore, a factor that influences monoclonal antibody effectiveness. To the best of our knowledge, these results represent the first rational treatment for improving low sperm motility in these severely affected patients.
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Anticuerpos Monoclonales/farmacología , Interleucina-1/inmunología , Interleucina-6/inmunología , Semen/metabolismo , Motilidad Espermática/efectos de los fármacos , Traumatismos de la Médula Espinal/fisiopatología , Factor de Necrosis Tumoral alfa/inmunología , Adulto , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Masculino , Traumatismos de la Médula Espinal/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
PURPOSE: Patients with spinal cord injuries have abnormal seminal plasma, which contributes to impaired sperm motility and viability. A common finding in these patients is an elevated leukocyte count in semen. We examined the prostatic tissue of spinal cord injured patients vs young healthy controls to determine whether a pathological process related to the prostate gland is a possible source of leukocytospermia. MATERIALS AND METHODS: Seven men with a mean age of 26.1 years with spinal cord injury and 4 controls with a mean age of 35.0 years underwent standard transrectal ultrasound guided prostate biopsy. Semen analyses were performed prior to biopsies. At least 3 biopsy cores were obtained from each prostate and all underwent routine hematoxylin and eosin staining. RESULTS: No significant abnormalities were found in any prostate biopsy cores. Two spinal cord injured patients had minor evidence of prostatic inflammation in 1 core. No inflammation was seen in any control specimens. None of the specimens showed signs of malignancy. CONCLUSIONS: Prostate biopsies obtained in this study did not show any signs of a chronic or acute significant inflammatory process that could explain increased leukocytospermia seen in patients with spinal cord injury.