Interstitial pneumonitis associated with leuprorelin acetate for a prostate cancer: A case report.

INTRODUCTION: Androgen deprivation therapy remains the essential treatment for disseminated prostate cancer. Interstitial pneumonitis following this therapy has been documented for just a few cases. However, reported cases frequently describe the onset of symptoms after recent administration (days or a few weeks) of both GnRH analogues and androgen antagonists, which makes the precise individual impact of each treatment difficult to estimate. CASE REPORT: This report presents a case of a 94-year-old patient with interstitial pneumonitis whose onset started three months after the first dose of leuprorelin and bicalutamide for a metastatic prostate cancer. MANAGEMENT AND OUTCOME: Once other possible diagnosis were ruled out, empiric corticosteroid treatment was initiated within 48 h of the admission. A spectacular clinical and radiological improvement was observed after 3 doses of steroids, enabling the patient to recover his basal respiratory situation. We considered that the most probable cause was toxic interstitial pneumonitis induced by leuprorelin. DISCUSSION: To our knowledge, it describes the longest interval between last administration of antiandrogen therapy and the development of pneumonitis. This fact may support a direct relation with leuprorelin, whose serum levels remain high for months because of its long-acting depot formulation.

[Aggressive variants of castration resistant prostate cancer (CRPC): neuroendocrine prostate cancer.] / Variantes agresivas de cáncer de próstata resistente a la castracion (CPRC): cáncer de próstata neuroendocrino.

Castration resistant prostate cancer (CRPC) is characterized by an important molecular, pathological and clinical heterogeneity. Although most of them present androgen receptor (AR) signal dependence, there are independent phenotypes. Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype with adverse prognosis due to late diagnosis, heterogeneous clinical features and lack of effective systemic treatments. Platinum based chemotherapy is the standard treatment, presenting short limited responses. There are pure forms or mixed with adenocarcinoma component. De novo diagnosis is unusual, being more frequent in advanced stages of prostate cancer, as a consequence of the inhibition of androgen receptor performed by various treatments. Thus, it could represent an aggressive evolution from carcinoma through a NEEpithelial transdifferentiation. Development of preclinical studies has permitted characterization of molecular and genomic alterations associated with this evolution and they may help to develop new therapeutic targets. Over the last years, there have been important advances in identification and characterization of clinical and pathological CRPC variants. NEPC is one of the most aggressive subtypes. A better knowledge of the disease biology is necessary to develop new treatments and biomarkers that help to manage this aggressive variant of PC.

Variantes agresivas de cáncer de próstata resistente a la castración (cprc): cáncer de próstata neuroendocrino / Recommendations for follow up in castration resistant prostate cancer

El cáncer de próstata resistente a la castración (CPRC) se caracteriza por una importante heterogeneidad molecular, patológica y clínica. Aunque la mayoría presentan dependencia a la señal del receptor androgénico (RA), existen fenotipos independientes a ésta. El cáncer de próstata neuroendocrino (CPNE) es un subtipo histológico poco frecuente y de pronóstico adverso debido al diagnóstico tardío, características clínicas heterogéneas y a la falta de tratamientos sistémicos efectivos. El tratamiento estándar es la quimioterapia (QT) basada en platino, presentando respuestas de escasa duración. Existen formas puras o mixtas con un componente de adenocarcinoma. Es raro su diagnóstico de novo, siendo más frecuente su aparición en estados avanzados del cáncer de próstata (CP), como consecuencia de la inhibición del receptor androgénico (RA) realizada por diversos tratamientos. Así, podría representar una evolución agresiva desde un adenocarcinoma (CPAD) a través de un mecanismo de transdiferenciación epitelio-NE. El desarrollo de estudios preclínicos han permitido la determinación de alteraciones moleculares y genómicas asociadas a esta evolución y que pueden ayudar al desarrollo de nuevas dianas terapéuticas. En los últimos años se han producido importantes avances en la identificación y caracterización de variantes clínicas y patológicas del CPRC. El CPNE es uno de los subtipos más agresivos. Un mayor conocimiento de la biología de la enfermedad es necesario para desarrollar nuevos tratamientos y biomarcadores que ayuden al manejo de esta variante agresiva del CP

Castration resistant prostate cancer (CRPC) is characterized by an important molecular, pathological and clinical heterogeneity. Although most of them present androgen receptor (AR) signal dependence, there are independent phenotypes. Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype with adverse prognosis due to late diagnosis, heterogeneous clinical features and lack of effective systemic treatments. Platinum based chemotherapy is the standard treatment, presenting short limited responses. There are pure forms or mixed with adenocarcinoma component. De novo diagnosis is unusual, being more frequent in advanced stages of prostate cancer, as a consequence of the inhibition of androgen receptor performed by various treatments. Thus, it could represent an aggressive evolution from carcinoma through a NEEpithelial transdifferentiation. Development of preclinical studies has permitted characterization of molecular and genomic alterations associated with this evolution and they may help to develop new therapeutic targets. Over the last years, there have been important advances in identification and characterization of clinical and pathological CRPC variants. NEPC is one of the most aggressive subtypes. A better knowledge of the disease biology is necessary to develop new treatments and biomarkers that help to manage this aggressive variant of PC