Intermittent androgen deprivation (IAD) in patients with biochemical failure after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer.

We report a study in which our objective was to analyze the clinical response during IAD in patients with biochemical failure after RRP for clinically localized prostate cancer. Between February 1994 and May 1996, 34 patients who exhibited a primary postoperative decrease in PSA to below the detection limit after RRP and then showed PSA progression during follow-up were included as group 1 and 17 patients in whom PSA did not decrease after RRP were included as group 2. Patients were offered IAD when PSA progressed over 0.4 ng/ml in group 1 and over 4.0 ng/ml in group 2. Median follow-up is 184 weeks in group 1 and 206 weeks in group 2. The median time "off" therapy increased from 25% (1st cycle) to 68.7% (5th cycle) of the entire cycle in group 1 and from 33.3% to 58.3% in group 2. Nine out of 12 cases with Gleason score > or =8 failed to respond to IAD and all developed metastatic and/or local failure. No case with Gleason score <7 failed to respond to IAD. Our conclusions suggest that IAD may be effective in patients with biochemical progression after RRP. In our experience, Gleason score seems to be an important variable.

Intermittent androgen deprivation (IAD) in patients with localized prostate cancer and a biochemical progression after radical prostatectomy.

BACKGROUND: To analyze the modifications in serum PSA levels during IAD in patients with an initial PSA progression after radical retropubic prostatectomy (RRP). METHODS: Between February 1994 and May 1996, 34 consecutive patients with an initial PSA progression (> 0.4 ng/ml) after RRP were selected. All men had localized adenocarcinoma of the prostate, stage pT2 pN0 M0. Patients were offered IAD when PSA progressed over 0.4 ng/ml. The initial treatment period with complete androgen deprivation (CAD) lasted 24 weeks in all cases. After, an acceptable nadir PSA level was considered to be a value < or = 0.4 ng/ml. CAD was then with held until serum PSA increased to a value over 0.4 ng/ml. RESULTS: Follow-up ranges from 144 to 228 weeks. The median time for the first 5 treatment cycles was 32, 24, 28, 32 and 32 weeks respectively, with a median time "off" therapy that increased from 8 weeks (first cycle) to 22 weeks (fifth cycle). The median nadir PSA value during "on" treatment period was 0.20 ng/ml in all 5 cycles. So far, in none of the patients did a serum PSA fail to decrease during "on" treatment period. CONCLUSIONS: We suggest that IAD may be an effective therapy in patients with an initial PSA progression after RRP. However, large prospective studies are needed to confirm these results and to better understand the meaning of PSA variations.

[Role of nitric oxide in the urogenital system: physiology and pathology]. / Ruolo dell'ossido nitrico nell'apparato genito-urinario: fisiologia e patologia.

A review has been made on the role of nitric oxide in the physiology and pathophysiology of penis, bladder, prostate and the nervous structures involved in the urinary control. NO is an essential mediator in penile erection and his action can be modulated by sildenafil. Nitric oxide could be involved in bladder detrusor relaxation and in the development of interstitial cystitis. Little is known about the role of nitric oxide in the physiology and pathophysiology of the prostate: this molecule is released by the epithelial and stromal cells of the prostate, and by the prostatic nerves. Actually some studies hypothesize a role played by nitric oxide in benign prostatic hyperplasia development.

Hormone-refractory prostate cancer? Anti-androgen withdrawal and intermittent hormone therapy.

OBJECTIVE: To separate hormone-dependent from hormonally relapsed prostate cancers, a D3 category has been proposed. The term has become synonymous with a hormone-refractory state with the implication that any further hormonal treatment would not be beneficial. In this review we examine some data on androgen receptor expression, anti-androgen withdrawal syndrome and intermittent androgen deprivation (IAD) in patients with advanced prostate cancer. MATERIALS: The literature on the mechanism of the withdrawal phenomenon in patients with prostate cancer submitted to hormone therapy was reviewed. Experimental and clinical data are reported. RESULTS: The progression of prostate cancer in patients treated with combined androgen blockade (CAB) is associated with the activation of previously androgen-repressed genes, some of which may code for autocrine and paracrine growth factors that substitute for androgens in maintaining the viability of the tumorigenic stem cells. If androgens are replaced before progression begins, the surviving stem cells should give rise to an androgen-dependent tumor, which would be amenable to retreatment by CAB. This theory provides the rationale for intermittent androgen deprivation. We suggest that IAD could be more effective in patients with initial prostate-specific antigen (PSA) progression after radical prostatectomy. CONCLUSIONS: Response to withdrawal therapies or second-line treatments is an example of a "hormonal" therapy that may benefit a proportion of patients with hormone-refractory disease, suggesting that the tumor is still androgen-dependent. Whether IAD enhances progression-free survival or overall survival must be verified in randomized clinical trials. Until further studies have been completed, the therapeutic concept of IAD should be treated as experimental.

[Limitations on the interpretation of prostate-specific antigen serum levels]. / Limiti nell'interpretazione dei livelli sierici dell'antigene specifico prostatico (PSA).

Recent data suggest that PSA expression can be directly influenced by some factors, independently from the variation in prostate cell growth. Some growth factors such as fibroblast growth factor, transforming growth factor beta and epidermal growth factor, seem to be directly involved in the regulation of mRNA-PSA expression, whereas androgens could have an indirect activity. On the basis of these experimental data, this review tries to analyze some limits of PSA and some recent data on the role of PSA-isoforms, in particular in the follow-up of prostate cancer patients submitted to radical prostatectomy or hormone-therapy. Moreover, relevant informations can be obtained analyzing the variance of PSA in patients submitted to intermittent androgen deprivation.

Penile metastasis from carcinoma of the prostate in a patient with high serum prostate specific antigen levels.

Prostatic carcinoma metastasizing to the penis is rare. Prognosis is poor with survival ranging from 1 to 24 months. A patient with prostate cancer and a serum Prostate Specific Antigen (PSA) level over 200 ng/ml, submitted to radical retropubic prostatectomy (RRP) and after 2 months presenting with two painful nodules in the penis, is described.

Hormonal profile of patients with Leydig cell tumors: a urologic cause of gynecomastia.

It is possible to hypothesize an alternative role for estrogens as a predisposing factor for testicular abnormalities: estrogen exposure during development in perinatal life may initiate cellular changes which would require estrogen and/or androgen later in life for promotion to hyperplasia or neoplasia. We reviewed the literature on Leydig cell tumors and the hormonal modifications they induce. In adult patients with Leydig cell tumors, although the serum estrogen (E2) and testosterone (T) varied, the T/E2 ratio was constantly low, and the chorionic gonadotropin administration produced an higher estrogen response than in normal men. Hormonal follow-up after orchidectomy for Leydig cell tumors has not been frequently described, and both normalization and lack of normalization of T, E2, gonadotropins and hCG have been reported. In the last part of the review we analyzed the principal urologic causes of gynecomastia in men. Testicular failure, either primary or secondary is a frequently found etiology for gynecomastia. Leydig cell tumors may elevate estrogen levels, and approximately 20% of patients with these tumors have gynecomastia.

Peptide growth factors: clinical and therapeutic strategies.

The literature contains many accounts of studies in which tumour growth has been accelerated by administration of a particular mitogen and the response then inhibited by co-administration of the corresponding antagonist. Much effort has been focused on the development of cytokine or growth factor antagonists. Like most other cancer therapies, biological therapies will undoubtedly have undesirable toxicities because the proteins they target may not be unique to malignant cells. We reviewed the clinical and therapeutic potential of growth factor agonists and antagonists in some non urologic and urologic diseases. In a recent report we demonstrated that both androgen and antiandrogen treatments enhance the proliferation rate of the hormone-dependent prostate cancer cell line LNCaP, expressing a mutated androgen receptor. Simultaneous treatment with 1 nM R1881 and 100 nM OH-Flutamide, completely counteracted the androgen-induced increase of Epidermal Growth Factor (EGF) levels. Moreover we found that Testosterone, DHT and EGF are mainly concentrated in the periurethral zone in human BPH and long term treatment with Finasteride and with Flutamide modify the distribution and concentration of these factors. Some authors analyzed whether and addition of aurin tricarboxylic acid (ATA) can reduce the growth rate of basic FGF-dependent cells in a manner similar to suramin.

Is medical therapy an expensive way for delaying surgery in BPH patients?

Nowadays, no medical therapy can be considered as a real and definitive alternative to surgery in the management of BPH patients. We considered pharmacologic approach as a treatment that may delay the need for surgery for BPH. In some cases a delayed therapy may continue for all patient life, excluding the need for TURP. The questions that we propose in the present review are: Is there always a role for a delayed medical therapy in the treatment of BPH patients? In which BPH patients a delayed medical therapy and in which instead an immediate surgery may be chosen? Which factors may influence this decision? A delayed medical therapy cannot be chosen in all BPH cases. Two factors can influence the evolution of the disease and the decision of the therapy: the first, natural history of BPH is related to BPH progression, and the second to patient characteristics. The role of growth factors in the natural history of BPH is investigated. Age of patient, his health condition and the presence of concomitant diseases are characteristics that may influence the therapeutic choice. In a young patient with good health condition and no concomitant diseases, the specific clinical phase of BPH is crucial to determinate the need for surgery of for medical delayed therapy. If there is a worsening health status or concomitant diseases as diabetes and hypertension that can increase the risk related to surgery in the future or can determine a more rapid evolution of BPH, TURP may be immediately recommended in all clinical phases of prostatic hyperplasia. The role of age in this therapeutic decision must be carefully examined.