Antonio Cardi

New perspective in the management of neuroendocrine differentiation in prostate adenocarcinoma

In this review, we will present some of the information that is known about neuroendocrine (NE) cells and differentiation in the prostate. We will then speculate on the potential role that NE differentiation in prostate carcinoma may play and how this differentiation may be clinically analysed and treated. The androgen‐independent growth of prostate cancer can be caused by different mechanisms; one of these is receptor‐specific paracrine or autocrine growth modulation of human prostatic cancer cells by neuropeptides secreted by NE cells. Our results affirm that different methods of androgen deprivation can influence the serum chromogranin A (CgA) levels to different extents in prostate cancer. In particular, bicalutamide produces a significantly lower increase in serum CgA compared with castration therapy. In the light of other evidence that supports a significant relationship between serum CgA levels, tissue CgA expression and NE activity, we hypothesise that bicalutamide may reduce the risk of NE cell hyperactivation in prostate cancer.

Antiandrogen Monotherapy: Recommendations for the Treatment of Prostate Cancer

Objective: The concept of antiandrogens as monotherapy for the treatment of prostate cancer is discussed. Methods: Both Medline and Current Contents were used to identify studies on antiandrogen monotherapy in prostate cancer. We tried to analyze this database critically to estabilish whether or not there is evidence for using this monotherapy. Results: In particular, bicalutamide in monotherapy has been compared with castration in large international trials. Results show that antiandrogen monotherapy is inferior to castration in patients with metastatic tumour but the difference in median survival is limited. In locally advanced M0 prostate cancer bicalutamide 150 mg monotherapy seems equivalent to castration in terms of overall survival and time to progression. Analysis of quality of life showed that there is evidence of some benefits from bicalutamide when compared to castration in both sexual interest and physical capacity. Conclusion: Antiandrogens in monotherapy can be effective and well tolerated. However, more research is needed because none of the available compounds have definitively been proven to be equivalent to castration.

Prostate-specific Antigen Density Is a Good Predictor of Upstaging and Upgrading, According to the New Grading System: The Keys We Are Seeking May Be Already in Our Pocket

OBJECTIVE To analyze the performance of prostate-specific antigen density (PSAD) as a predictor of upstaging and prognostic grade group (PGG) upgrading. MATERIALS AND METHODS We retrospectively evaluated data on men with prostate cancer (PCa) treated with robot-assisted laparoscopic radical prostatectomy (RALP) at our center in 2014-2015. Preoperative PSAD was calculated. Bioptic and pathologic PGGs were also considered in the analysis. We defined upgrading as any increase in PGG after RALP; upstaging was the pathologic diagnosis of a clinically unsuspected stage ≥3a PCa. RESULTS Data on 379 patients were analyzed. Upgrading was found in 41.4% of the patients; 29% of the patients were upstaged. On multivariable analysis, core involvement and PSAD were found to be predictors of upgrading (odds ratio [OR] 1.017, 95% confidence interval [CI] 1.001-1.034, P = .039; and OR 3.638, 95% CI 1.084-12.207, P = .001, respectively). Furthermore, core involvement and PSAD were predictors of upstaging (OR 1.020, 95% CI 1.020-1.034, P = .003; and OR 5.656, 95% CI 1.285-24.894, P = .022, respectively). PSAD showed areas under the curve of 0.712 (95% CI 0.645-0.780, P = .000) and 0.628 (95% CI 0.566-0.689, P = .000) for the prediction of upgrading and upstaging, respectively. In a subpopulation of 90 patients theoretically eligible for active surveillance, 14% were found upstaged and 17% were upgraded. PSAD showed areas under the curve of 0.894 (95% CI 0.808-0.97, P = .000) and 0.689 (95% CI 0.539-0.840, P = .021) for the prediction of upgrading and upstaging, respectively. CONCLUSION PSAD is a valuable predictor of upgrading and upstaging in men with PCa who were candidates for surgery and is accurate in selecting patients for AS.

Combination Therapy With Rofecoxib and Finasteride in the Treatment of Men With Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH)

PURPOSE Cyclooxygenase-2 (COX-2) is expressed in human BPH tissue and displays either a pro-inflammatory effect or a proliferative effect on prostate cells. The aim of this study is to analyze whether combination therapy with rofecoxib, a COX-2 inhibitor, and finasteride offers an advantage compared to finasteride monotherapy in patients with BPH. MATERIALS AND METHODS This is a single centre unblinded trial. Forty-six consecutive men with LUTS and BPH were entered into the study and were randomized to receive rofecoxib 25mg/day plus finasteride 5mg/day (group B) versus finasteride 5mg/day alone (group A) for 24 weeks. Inclusion criteria included also a prostate size greater than 40 cc. The efficacy and safety of treatments were assessed at baseline and at week 4, 12 and 24. RESULTS In our population, both treatments (groups A and B) produced statistically significant improvements in total IPSS and Q(max) from baseline during follow-up, although they were very low in particular for the finasteride alone group at 4 weeks. We found that finasteride monotherapy produces very little improvement at the 1 month interval. In comparing group A with group B, a significantly higher improvement in IPSS (p=0.0001) and Q(max) (p=0.03) was obtained in group B at 4 weeks interval (% cases with IPSS reduction >4 points: group B=34.7, group A=0; % cases with Q(max) improvement >3 ml/s: group B=8.7, group A=0), whereas at week 24, the differences between the two treatments were not significant (p>0.05). CONCLUSIONS In our population, the advantage of the combination therapy compared to finasteride alone is significant in a short-term interval (4 weeks). It can be hypothesized that the association of rofecoxib with finasteride induces a more rapid improvement in clinical results until the effect of finasteride becomes predominant.

Which patients with prostate cancer are actually candidates for hormone therapy

In this article, we will try to address the following aspects: which factors are responsible of the introduction of new candidates for hormone therapy in prostate cancer, who are actually candidates for hormone therapy, classifying them on the basis of the stage of the disease, and which treatment modalities can be proposed for each candidate. Since the introduction of hormone therapy for the treatment of prostate cancer, there has been a debate about the optimal timing of hormone therapy. A modification in the timing of hormone therapy produced new candidates for hormone manipulation. In particular, the use of hormone treatment for younger patients, longer periods and early prostate cancer, absolutely requires a whole re-evaluation of which therapy is indicated and it may produce new problems such as higher risk of over-treatment, need of a better evaluation of quality of life in younger patients and the research for better tolerated therapies. Therapies that resist for longer periods without the production of a hormone-refractory disease are also required.