Longer time to testosterone recovery impacts favorably on outcomes for prostate cancer following androgen deprivation and radiotherapy.

PURPOSE: To evaluate the impact of sustained hypogonadism after androgen deprivation therapy (ADT) associated with radiotherapy in prostate cancer (PCa) patients with biochemical relapse-free survival (bRFS). METHODS: A retrospective cohort analysis of 213 consecutive PCa patients referred for radiotherapy plus ADT was carried out. Follow-up times including time to testosterone recovery (TTR) and bRFS were calculated from the end of ADT. Univariate and multivariate Cox regression analyses predicting bRFS were used. The optimal cutoffs for TTR and duration of ADT were determined using the maximally selected rank statistics (MSRS). RESULTS: After a median follow-up of 104 months, 18 patients relapsed among those who had recovered testosterone levels and 9 among those who did not. Median ADT duration was 36 months. The optimal cutoff for TTR was determined using MSRS. TTR >48 months was significantly associated with better bRFS (logrank, p < 0.0027). Five-year bRFS was 100% for >48 months vs. 85% for <48 months. TTR was the only significant variable for bRFS in multivariate Cox analysis. CONCLUSION: Our data show an association between longer TTR and bRFS values among PCa patients treated with ADT.

[Review of current treatment for hot flushes induced by androgen deprivation in prostate carcinoma]. / Revisión del tratamiento actual de los sofocos inducidos por deprivación androgénica en el carcinoma prostático.

Considering the currently increased incidence, prevalence and survival of prostate cancer, the management of hot flushes associated with LH-RH analog treatment must be taken into account. The most widely used and effective treatment is hormone replacement, though the latter is not without risks. It is presently possible to address hot flushes in these patients based on a broad range of treatment options in which hormone therapy may constitute a last option, due to the risk of tumor relapse or progression -- since prostate cancer is hormone sensitive. The present study reviews the currently used treatments and hygiene-dietary measures that may help reduce the symptoms. A review is made of both hormone and non-hormone therapies, based on the existing scientific evidence. Drugs such as the new antidepressants, gabapentin and clonidine may play an important role in the management of hot flushes. While the underlying mechanisms of action are varied, they are related to the complex feedback exerted by the sexual hormones upon the hypothalamic secretion of noradrenalin -- this being the principal etiological factor of hot flushes.

[Physiopathological mechanism of hot flushes-perspiration induced by androgen deprivation in prostate carcinoma]. / Mecanismo fisiopatológico de los sofocos-sudores inducidos por deprivación androgénica en el carcinoma prostático.

Hot flushes and perspiration are common problems during androgen deprivation therapy for prostate carcinoma, and largely contribute to worsen patient quality of life. Different hypotheses have been proposed to explain the underlying physiopathological mechanisms, though all are very complex, basically because of the multiple causal factors involved. The present review offers a pondered and updated perspective of the origin of hot flushes-perspiration in such patients. Negative feedback of the plasma sexual hormones upon the hypothalamic secretion of noradrenalin and serotonin appears to be the main cause. Likewise, the direct action of such mechanisms upon the LH-RH producing hypothalamic center located close to the thermoregulatory center, together with shortening of the thermoneutral interval, would also play a role. Improved understanding of the causal mechanism may help improve the treatment of such symptoms.

Trazodona: ¿Nuevo enfoque selectivo para el tratamiento de los sofocos generados por la deprivación androgénica en el carcinoma prostático? / Trazodone: A new selective approach to the treatment of hot flashes induced by androgen deprivation in prostate carcinoma?

El protagonismo creciente del carcinoma prostático en las sociedades desarrolladas hace que tenga que ser muy tenido en cuenta el balance beneficio-perjuicio de los tratamientos prestados. Dado el enfoque terapéutico cada vez más complejo del carcinoma prostático, hoy en día se requiere de una suma de conocimientos extensos. La deprivación androgénica juega un papel principal en esta patología. El tratamiento de la toxicidad derivada en forma de sofocos, síndrome metabólico, osteoporosis, trastornos cognitivos, etc., adquiere cada vez mayor interés. El tratamiento farmacológico de los sofocos pasa por un manejo hormonal no exento de riesgo oncológico a la par que de una toxicidad nada despreciable. Dentro del tratamiento no hormonal de esta patología juegan un papel destacado los antidepresivos. La trazodona, un antidepresivo SARI (inhibidores de la recaptación de serotonina/antagonista de la 2A), con un perfil de actuación más selectivo sobre los receptores implicados en los sofocos; podría ser de gran interés. Trazodona muestra una gran afinidad por los receptores 5-HT2A y una moderada afinidad por los receptores 5-HT1A. Como es conocido los niveles de serotonina (5-hidroxitriptamina o 5-HT) en mujeres postmenopáusicas están disminuidos, normalizándose con las terapias sustitutivas. Todo ello sugiere que la de privación abrupta de hormonas sexuales da lugar a una reducción en la circulación de serotonina, con el consiguiente aumento de sus receptores 5-HT2A hipotalámicos. Estos receptores estarían implicados en la patogénesis de los sofocos siendo su bloqueo una de las principales medidas terapéuticas. El uso de trazodona elevando las concentraciones de serotonina y bloqueando a los receptores 5-HT2A y 5-HT1A podría plantearse como un nuevo enfoque más de acorde con la fisiopatología de los sofocos. Estudios comparativos bien dirigidos son necesarios para dar respuesta en cuanto a su efectividad. Otras cuestiones pendientes serían las dosis y el tiempo de tratamiento más eficaz para el control de los sofocos (AU)

The growing relevance of prostate carcinoma in the developed world requires serious attention to focus on the risk-benefit relationships of the treatments used. Given the increasingly complex therapeutic approach to prostate carcinoma, an extensive range of knowledge is required. Androgen deprivation plays a central role in this disease. The management of androgen deprivation-derived toxicity in the form of hot flashes, metabolic syndrome, osteoporosis, cognitive disorders, etc., is of growing interest. The drug treatment of hot flashes involves hormone management that is not without oncological risk and moreover generates considerable toxicity. Antidepressants in turn play an important role in the non-hormone treatment of this disorder. Trazodone, a serotonin reuptake inhibitor/5-HT2A receptor antagonist affording more selective action upon the receptors implicated in hot flashes, could be of great interest. Trazodone shows great affinity for the 5-HT2A receptors and moderate affinity for the 5-HT1A receptors. Serotonin (5-hydroxytryptamine, or 5-HT) levels are known to be lowered in postmenopausal women, and normalize when replacement therapy is provided. This suggests that abrupt sexual hormone deprivation gives rise to a reduction in blood serotonin –with a subsequent increase in its hypothalamic 5-HT2A receptors. These receptors would be implicated in the physiopathology of hot flashes; as a result, the blocking of such receptors is one of the principal therapeutic measures. The use of trazodone, increasing the serotonin concentrations and blocking the 5-HT2A and 5-HT1A receptors, could be viewed as a novel management approach more in line with the physiopathology of hot flashes. Well designed comparative studies are needed to establish the efficacy of such treatment. Other issues pending clarification would be the most effective dose and duration of treatment for controlling hot flashes (AU)

Revisión del tratamiento actual de los sofocos inducidos por deprivación androgénica en el carcinoma prostático / Review of current treatment for hot flushes induced by androgen deprivation in prostate carcinoma

Dada la mayor incidencia, prevalencia y supervivencia del carcinoma prostático en la actualidad, el manejo de los sofocos derivados de su tratamiento con análogos LH-RH ha de ser muy tenido en cuenta. El tratamiento más utilizado y a la vez el más eficaz, es la sustitución hormonal pero este tipo de terapia no esta exenta de riesgos. Hoy por hoy es factible el abordaje de los sofocos de estos pacientes mediante un variado arsenal terapéutico en el cual el tratamiento hormonal puede quedar relegado al último lugar, dado el riesgo de recidiva o progresión tumora lal tratarse de un tumor hormonosensible. El objetivo de este trabajo es revisar los tratamientos utilizados actualmente y las medidas higiénico-dietéticas que pueden ayudar a disminuir la sintomatología. Se revisarán tanto los tratamientos hormonales como los no hormonales basados en su evidencia científica. Fármacos como los nuevos antidepresivos, la gabapentina y la clonidina podrían jugar un papel destacado en el manejo. Sus mecanismos de actuación aunque dispares, se enmarcan en el complejo sistema de retroalimentación ejercido por los niveles de hormonas sexuales sobre la secreción hipotalámica de noradrenalina, causa principal en la génesis de los sofocos (AU)

Considering the currently increased incidence, prevalence and survival of prostate cancer, the management of hot flushes associated with LH-RH analog treatment must be taken into account. The most widely used and effective treatment is hormone replacement, though the latter is not without risks. It is presently possible to address hot flushes in these patients based on a broad range of treatment options in which hormone therapy may constitute a last option, due to the risk of tumor relapse or progression – since prostate cancer is hormone sensitive. The present study reviews the currently used treatments and hygiene-dietary measures that may help reduce the symptoms. A review is made of both hormone and non-hormone therapies, based on the existing scientific evidence. Drugs such as the new antidepressants, gabapentin and clonidine may play an important role in the management of hot flushes. While the underlying mechanisms of action are varied, they are related to the complex feedback exerted by the sexual hormones upon the hypothalamic secretion of noradrenalin – this being the principal etiological factor of hot flushes (AU)

Mecanismo fisiopatológico de los sofocos-sudores inducidos por deprivación androgénica en el carcinoma prostático / Physiopathological mechanism of hot flushes-perspiration induced by androgen deprivation in prostate carcinoma

Los sofocos-sudores son problemas frecuentes durante el tratamiento con de privación androgénica en pacientes afectos de carcinoma prostático. Estos efectos secundarios contribuyen en gran medida al deterioro de la calidad de vida. Se han postulado diferentes hipótesis sobre los mecanismos fisiopatogénicos implicados, todos ellos de una alta complejidad debida básicamente a su multicausalidad. El objetivo de esta revisión es aportar una visión meditada y actualizada de su génesis. La retroalimentación negativa de las hormonas sexuales plasmáticas sobre la secreción hipotalámica de noradrenalina y serotonina serían la causa principal. Asimismo la acción directa de estos mecanismos sobre el centro hipotalámico productor de LH-RH cercano al centro termorregulador, junto al acortamiento del intervalo termo neutral también estarían implicados. La mejor comprensión de su mecanismo de producción nos puede hacer enfocar mas correctamente su tratamiento (AU)

Hot flushes and perspiration are common problems during androgen deprivation therapy for prostate carcinoma, and largely contribute to worsen patient quality of life. Different hypotheses have been proposed to explain the underlying physiopathological mechanisms, though all are very complex, basically because of the multiple causal factors involved. The present review offers a pondered and updated perspective of the origin of hot flushes-perspiration in such patients. Negative feedback of the plasma sexual hormones upon the hypothalamic secretion of noradrenalin and serotonin appears to be the main cause. Likewise, the direct action of such mechanisms upon the LH-RH producing hypothalamic centerlocated close to the thermoregulatory center, together with shortening of the thermo neutral interval, would also play a role. Improved understanding of the causal mechanism may help improve the treatment of such symptoms (AU)

[Single fraction boost with high dose rate interstitial brachytherapy in conservative treatment of breast carcinoma]. / Sobreimpresión en fracción única con braquiterapia intersticial de alta tasa en el tratamiento conservador del carcinoma de mama.

INTRODUCTION: We evaluated the effectiveness of interstitial high dose rate brachytherapy as a single fraction boost to the surgical bed in patients with breast cancer undergoing conservative treatment. The comparison was with the alternative of electron boost. MATERIALS AND METHODS: Between April 1999 and December 2000, we conducted a prospective study of 84 patients with infiltrative breast carcinoma treated with conservative surgery, with free margins. This was followed by external radiotherapy to the breast of up to 46 Gy and one application of brachytherapy with needles inserted into the surgical bed, and administering 7 Gy to 90% with high dose rate (HDR). RESULTS: With a mean follow-up of 43 months, only one patient had therapeutic failure in the implant area, and local control was 98.5%. Another patient had a 2nd tumour in a different quadrant and 3 developed metastasis. Survival at 5 years was 98.7%. Acute toxicity was minimal, with excellent or good cosmetic appearance in 95%. CONCLUSIONS: Brachytherapy with high dose rate as single fraction boost in conservative treatment of breast carcinoma is simple, fast, well tolerated, with excellent local control, good cosmetic appearance, and with minimal late-onset toxicity.

Sobreimpresión en fracción única con braquiterapia intersticial de alta tasa en el tratamiento conservador del carcinoma de mama / Single fraction boost with high dose rate interstitial brachytherapy in conservative treatment of breast carcinoma

Introducción. Evaluamos la eficacia de la sobreimpresión del lecho quirúrgico con braquiterapia intersticial de alta tasa de dosis, en fracción única en pacientes con cáncer de mama, tratadas con tratamiento conservador, como alternativa a la sobreimpresión con electrones. Material y métodos. Entre abril de 1999 y diciembre de 2000, hemos realizado un estudio prospectivo sobre 84 pacientes con carcinoma infiltrante de mama sometidas a cirugía conservadora, con márgenes libres, seguida de radioterapia externa sobre la mama hasta 46 Gy y una aplicación de braquiterapia con agujas en el lecho quirúrgico, dando 7 Gy al 90% con alta tasa. Resultados. Con un seguimiento medio de 43 meses, sólo una paciente ha recaído en zona de implante siendo el control local del 98,5%. Otra paciente presentó un segundo tumor en un cuadrante distinto y tres desarrollaron metástasis. La supervivencia a 5 años es del 98,7%. La toxicidad aguda ha sido mínima, con estética excelente o buena en el 95%. Conclusiones. La braquiterapia con alta tasa en fracción única, como sobreimpresión en el tratamiento conservador del cáncer de mama, es bien tolerada, sencilla y rápida, consiguiendo un control local excelente, con buen resultado estético y una mínima toxicidad tardía

Introduction. We evaluated the effectiveness of interstitial high dose rate brachytherapy as a single fraction boost to the surgical bed in patients with breast cancer undergoing conservative treatment. The comparison was with the alternative of electron boost. Materials and methods. Between April 1999 and December 2000, we conducted a prospective study of 84 patients with infiltrative breast carcinoma treated with conservative surgery, with free margins. This was followed by external radiotherapy to the breast of up to 46 Gy and one application of brachytherapy with needles inserted into the surgical bed, and administering 7 Gy to 90% with high dose rate (HDR). Results. With a mean follow-up of 43 months, only one patient had therapeutic failure in the implant area, and local control was 98.5%. Another patient had a 2nd tumour in a different quadrant and 3 developed metastasis. Survival at 5 years was 98.7%. Acute toxicity was minimal, with excellent or good cosmetic appearance in 95%. Conclusions. Brachytherapy with high dose rate as single fraction boost in conservative treatment of breast carcinoma is simple, fast, well tolerated, with excellent local control, good cosmetic appearance, and with minimal late-onset toxicity