Do PHI and PHI density improve detection of clinically significant prostate cancer only in the PSA gray zone?

OBJECTIVES: Prostate health index (PHI) is a predictive biomarker of positive prostate biopsy. The majority of evidence refers to its use in the PSA gray zone (4-10 ng/mL) and negative digital rectal exam (DRE). We aim to evaluate and compare the predictive accuracy of PHI and PHI density (PHId) with PSA, percentage of free PSA and PSA density, in a wider range of patients for the detection of clinically significant prostate cancer (csPCa). METHODS: Multicenter prospective study that included patients suspicious of harboring prostate cancer. Non-probabilistic convenience sampling, where men who attended the urology consultation were tested for PHI before prostate biopsy. To evaluate and compare diagnostic accuracy AUC and decision curve analysis (DCA) were calculated. All these procedures were performed for the overall sample and the following subsamples: PSA < 4 ng/ml; PSA 4-10 ng/ml; PSA 4-10 ng/ml plus negative DRE and PSA > 10 ng/ml. RESULTS: Among the 559 men included, 194 (34.7%) were diagnosed of csPCa. PHI and PHId outperfomed PSA in all subgroups. PHI best diagnostic performance was found in PSA 4-10 ng/ml with negative DRE (sensitivity 93.33, NPV 96.04). Regarding AUC, significant differences were found between PHId and PSA in the subgroup of PSA 4-10 ng/ml, whatever DRE status. In DCA, PHI density shows the highest net benefit. CONCLUSIONS: PHI and PHId outperfom PSA in csPCa detection, not only in the PSA grey zone with negative DRE, but also in a wider range of PSA values. There is an urgent need of prospective studies to established a validated threshold and its incorporation in risk calculators.

Small cell metastatic prostate cancer with ectopic adrenocorticotropic hormone hypersecretion: a case report.

Small cell prostate cancer (SCPC) is a rare entity with an incidence of 0.5-2% of all prostate carcinomas. SCPC is characterized by low prostate specific antigen (PSA) levels, lack of response to androgen deprivation therapy and distal dissemination with visceral metastases at diagnosis in 70% of patients. Moreover, it can present as paraneoplastic syndromes including Cushing's syndrome or hypercalcemia, which worsens prognosis. We report a case of 65-year-old male attending the emergency department with hyperaldosteronism clinic. After completing the study, locally advanced SCPC with multiple metastatic adenopathies is diagnosed. It shows low PSA levels, high adrenocorticotropic hormone (ACTH) levels and an immunohistochemistry (IHC) showing positivity for CD56 and synaptophysin. He presented a poor evolution of hypercortisolemia in the context of a paraneoplastic syndrome with ACTH hypersecretion. SCPC is a challenge in its diagnosis and treatment due to few reports in the literature. As this tumor can go unnoticed, a high diagnostic suspicion is necessary, being the biopsy the gold standard for its confirmation. Pathological study with IHC analysis, including neuroendocrine (NE) markers, are essential for its diagnosis. Despite systemic chemotherapy, prognosis is poor because of local and distant aggressiveness. Hence, the aim of treatment is to control cancer trying to offer a good quality of life. New lines of treatment are being investigated.