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The knowledge of inter- and intrafraction motion and deformations of the intrapelvic target volumes (prostate, seminal vesicles, prostatectomy bed and lymph nodes) as well as the main organs at risk (bladder and rectum) allow to define rational clinical to planning target volume margins, depending on the different radiotherapy techniques and their uncertainties. In case of image-guided radiotherapy, prostate margins and seminal vesicles margins can be between 5 and 10mm. The margins around the prostatectomy bed vary from 10 to 15mm and those around the lymph node clinical target volume between 7 and 10mm. Stereotactic body radiotherapy allows lower margins, which are 3 to 5mm around the prostate. Image-guided and stereotactic body radiotherapy with adequate margins allow finally moderate or extreme hypofractionation., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Liver, kidney, and gastrointestinal tissues are well known to express UDP-glucuronosyltransférase (UGT) enzymes which conjugate exogenous compounds. This mechanism is extremely important to eliminate several compounds from the body. Recent studies have shown that, in addition to the liver and kidney, a large number of tissues, namely the prostate and skin, also express UGT which are capable of inactivating steroids. This mechanism may be a means to modulate the action of steroids in these tissues.

THE "ANDROPAUSE": Also called the "male menopause" or "partial androgen deficiency of the aging male" etc., corresponds to the age at which the progressive decrease in androgen activity reaches a pathogenic threshold. Surveys made in various countries since the seventies conclude that testosterone blood levels start to decrease after the age of 25 and that 20 to more than 50% of the male population no longer benefit from optimal androgen stimulation after the age of 60. THE CONSEQUENCES OF HYPOANDROGENISM: The subsequent progressive hypoandrogenism participates in inducing the commonly-observed clinical symptoms (fatigue, morosity, weight loss, lack of interest in sexual activity); the most specific of which is the disappearance or rarification of "automatic" nocturnal or matinal erections. This appears to influence the prostatic pathology and the frequent cardiovascular risk factors, which, far more than a problem of erection, is a major public health issue. A COMPLEX BIOLOGICAL DIAGNOSIS: Added to the abnormalities in production and transport of testosterone are the abnormalities in its metabolisation by the target tissues. These abnormalities are often undetected in present day blood controls and may explain the elevation in the hepatocyte of SHBG synthesis, the relative inhibition of GnRH pulses and LH secretion in the hypothalamus and the pituitary gland and, in the arterial wall (including penile vascularisation) and the prostate, some of the frequent functional and histological disorders. In current practice today, the best approximation of androgen potential is obtained by the comparison of total testosterone concentrations and SHBG, measurements that require relatively reliable standardised kits., Therapeutic Choice: Optimal replacement therapy, for some authors, must mimic the physiology of the young man and above all maintain or reinforce the estrogenic effects of testosterone, related to its aromatisation into estradiol and supposedly beneficial for the cardiovascular system and the bone. For other, the androgenic effects, enhanced by the 5 alpha reduction into dihydrotestosterone (DHT), should be reinforced in older men because the estrogenic effects are ineffective on bone and most of the other targets, and are probably pathogenic for the prostate. This debate is extremely important since the various formulations of androgens authorized by the French Medicines agency (AFSSAPS) induce clearly differing estradiol/DHT plasma ratios.

A better understanding of the rich autonomic innervation of the prostate allows more effective treatment of voiding disorders secondary to benign prostatic hyperplasia. The glandular contingent possesses mainly cholinergic innervation (M2 muscarinic receptors). Smooth muscle cells are richly supplied with alpha and beta catecholaminergic receptors, involved in muscle contraction and muscle relaxation, respectively, but they may also be involved in growth. These alpha receptors, divided into 2 families (alpha 1 and alpha 2), belong to the family of G protein-coupled seven membrane-spanning helix receptors. The genes, followed by the recombinant proteins of 3 subtypes of alpha 1 receptors have been described: alpha 1-a, -b, -d. In the prostate, these receptors are predominantly located in the stroma, mainly in the centroprostatic region. The mRNA present mainly code for the alpha 1a subtype. The use of specific agonists and antagonists shows that these receptors control smooth muscle contraction according to a mechanism initially considered to be of the alpha 1a type. However, their low affinity for prazosin and the development of new alpha 1 blocking agents is in favour of the involvement of a different functional subtype: alpha 1L. This difference could be explained by a different conformation of the receptor or by different coupling mechanisms. The subtype involved in prostatic smooth muscle contraction has yet to be characterized.

Growth and development of the prostate depend on androgen action and other factors. Androgens act directly by specific nuclear receptors and induce or control many effects mediated by peptide growth factors on both epithelial and stromal cells. The major important peptide growth factors detected in the prostate are Fibroblast Growth Factors, Transforming Growth Factors, and Epidermal Growth Factor. These factors are not prostate specific. They are produced by epithelial or stromal cells and regulate the growth of these two cell compartments through autocrine or paracrine pathways. Overproduction of these factors or modification in affinity or number of cell receptors may participate in the two main prostatic pathologies: benign hyperplasia or adenocarcinoma. Recently, other factors have been evidenced in the prostate: Interleukine 6, Nerve Growth Factor or Insulin-like Growth factors. The study of the localization and the effects of these factors may be crucial to understand the prostatic development and diseases and may suggest new targets for therapy.

There is less knowledge of androgen receptors than of oestrogen receptors but, in recent years, important progress has been made. The author thus describes the physico-chemical properties of the androgen receptors. He discusses also the problems raised by their estimation. The exchange techniques are practically unusable as the androgen receptors are easily destroyed even at 15 degrees C. The author proposes and describes another method which isolates the hormone-receptor complex with protamine sulphate. He also considers the prospects of these receptor estimations in prostatic disease, e.g. androgen-dependent adenoma. The absence of androgen receptors in testicular feminisation syndrome finally permits excellent illustration of the importance of the study of receptors in the understanding of cellular insensivity to a hormone.

Spirolactones (spironolactone, potassium canrenoate) may produce secundary sexual effects such as gynecomastia in man and menstrual disturbances in women. The mechanism of action of the antiandrogenic effects has been studied in man and rat. Acute i.v. injection of potassium canrenoate into man results in a decrease of plasma testosterone, without any change of gonadotropins. This decrease might be due to an impaired testicular steroidogenesis. On the other hand, spirolactones have an antiandrogenic effect at the target cells level. They do not modify the prostate 5alpha-reductase activity; however, they do inhibit the binding of androgens to their receptors. Thus the spirolactones interact with both biosynthesis and peripheral action of androgens.

Sulpiride or Dogmatil (Delagrange, Paris) was injected to male rats at the rate of 40 mg/day for either 10 or 20 days. Ponderal fluctuations of the accessory organs followed by a quantitative analysis of fructose and of serum acid phosphatases issued from testis epididymis and prostates (PAP) were studied. The coagulating glands alone reacted strongly and their initial weight doubled in 20 days. On the contrary, the fructose decreased sharply in all accessory glands especially in the coagulating glands. The PAP decreased slightly. The fact the concentration of serum PAP remained relatively high even in the castrated males, can be explained by the increase in the lysosomial activity due to retention and diminution of secretion granules. Fructose and PAP are conditioned by androgens and their quantitative decrease suggests that the testosterone level decreased. Hyperprolactinemia induced by Sulpiride is concomittent to testosterone diminution and the effect of each hormone cannot easily be separated. In the castrated animals the effects of Sulpiride were minimized due to the difficulty in observing significant variations between treated and untreated castrates.

Prolactin plays a peripheral role in male reproductive function just as it does in female function. Prolactin, through the medium of immunocytochemistry acts on testicular steroidogenesis through prolactin receptors which are sited on the Leydig cells. It alters the number of LH receptors and therefore the sensitivity of the testis to central stimulation and equally interferes with androgen synthesis. In the areas of physiological concentration the principal effect seems to be to stimulate secretion of testosterone by keeping up the number of LH receptors; but when there is acute hyperprolactinaemia, testosterone secretion is lowered or perhaps not changed at all because of a "post-receptor effect", in spite of there being larger numbers of LH receptors. The direct effect of prolactin on spermatogenesis has not yet been worked out and the results that have been obtained are controversial. Prolactin exerts a direct stimulating effect on the growth of prostatic cells working synergistically with testosterone through specific prolactin receptors. It could play a role in certain cancers of the prostate.