[Prognostic factors and response predictors in castration resistant prostate cancer.] / Factores pronósticos y predictores de respuesta en cáncer de próstata resistente a la castración.

Prostate cancer is a health problem in many Countries worldwide. Understanding the essential function of androgens in the prostate physiology led to the development of hormonal blockade as a therapeutic option in advanced disease, with limited response with time and development of resistance. In this stage, where castration resistant prostate cancer (CRPC) is defined, it is associated with poor prognosis because survival varies between 18 and 24 months. Even with castration levels, tumors are dependent on the functional androgen receptor (AR). In this paper, we analyze pretreatment clinical parameters such as prognostic or progression-predictive biomarkers, castration resistance mechanisms, the development of new technologies for the use of the so called liquid biopsies from biological ayufluids and the identification of circulating tumor cells as CRPC response and progression biomarkers. Currently ongoing clinical trials are partially oriented to the search of new prognostic and predictive biomarkers, that will enable to open up precision medicine and so to improve oncological patient's quality of life with it.

[Immunotherapy in castration resistant prostate cancer.] / Inmunoterapia en cáncer de próstata resistente a la castración.

We review the role of immunotherapy in castration resistant prostate cancer. Two immunotherapeutic strategies have been applied, isolated or in combination, either with each other or with other agents with demonstrated efficacy in this scenario that would play a role as immunomodulators: vaccines or monoclonal antibodies aimed to block immune response checkpoint inhibitors. Although CRPC presents, a priori, characteristics suggesting that immunotherapy may play a relevant role as a therapeutic strategy, its clinical application has demonstrated a limited and heterogeneous activity, in terms of proportion of responders and response intensity. Generally, the objective response rate is very low, although, in patients who have response it is possible to detect a clear, long-lasting benefit. Only the autologous vaccine Sipuleucel T has demonstrated an overall survival increase in patients with good prognosis criteria. In these treatments, it is characteristic that no progression free survival increase is visible due to its action mechanism. PSA evolution may not be considered a surrogate variable of radiological response or clinical benefit in this environment either. It is necessary to identify what patient's or tumor's characteristics are able to maximize the response. An important limitation is the absence of response predictive biomarkers that serve for patient preselection. As a general rule, the best responses with isolated immunotherapeutic treatments have been observed in patients with low tumor load, which may suggest that their optimal application could be in earlier phases of the disease (high risk localized, biochemical failure, etc) Combination strategy, without doubt the one with best future, is based on additional treatments increasing cell lysis with the subsequent antigen exposure and/ or producing an immunomodulatory effect that can surmount tumor induced immunologic tolerance. The results obtained suggest that immunotherapy may be more effective in combined therapy with other active therapies (abiraterone, enzalutamide, Radium 223, docetaxel) in a fight to achieve disease chronification.

[The role of chemotherapy in the treatment of hormone sensitive metastatic prostate cancer.] / Papel de la quimioterapia en el tratamiento del cáncer de próstata metastásico hormonosensible.

OBJECTIVE: Several studies have assessed the role of adding chemotherapy to hormonal treatment for metastatic hormone-sensitive prostate cancer (MHSPC). The objective of this manuscript is to review these studies and to provide recommendations for the management of these patients. METHODS: We identified published clinical trials comparing hormone blockade (HB) with HB plus docetaxel as first-line treatment of HSMPC and we analyzed their results in terms of efficacy and toxicity. RESULTS: Of the 3 trials published, two demonstrated increased overall survival by adding docetaxel to the first-line treatment of MHSPC (CHAARTED and Stampede-Docetaxel studies) and the third one did not show such an advantage (GETUG-AFU15). In the CHAARTED study, the survival advantage was limited to patients presenting high tumor volume. Toxicity was increased in patients who received docetaxel. CONCLUSIONS: The addition of docetaxel to treatment with HB should be considered in patients with MHSPC, especially in those with high tumor volume. However, the toxicity and recent results of trials performed with abiraterone in MHSPC should also be taken in consideration.

[Evolution from Percutaneous nephrolithotomy to Mini-PCNL in supine position on the treatment of complex renal calculi: feasibility study.] / Evolución de nefrolitotomía percutánea estándar a mini­NLP en posición supino en el tratamiento de la litiasis renal compleja: estudio de viabilidad.

OBJECTIVES: Mini-PCNL is a potentially less invasive technique than standard percutaneous nephrolithotomy (PCNL). We present our experience and results comparing both approaches in large burden complex renal calculi. METHODS: Prospective non randomized study comparing PCNL (24/26F nephroscope; Group A) and Mini-PCNL (15/18F; Group B) perioperative and postoperative results, in 40 (20 each group) consecutive patients between 2013 and 2014. We analyze demographic data, hemoglobin drop, urine culture, stone characteristics, operative time, puncture, number and size of the tract, disintegration energy sources, nephrostomy placement, hospital stay, stone free rate and Clavien-Dindo complications. RESULTS: Evolution has shown growth for Mini-PNL, with the last 17 consecutive cases performed by this approach. No preoperative differences in laterality, age, gender or ASA were found; but there were differences in BMI (median Group A: 26.35 kg/m2; Median Group B: 33.05 kg/m2, p = 0.008). Median calculi surface area (SA = length × width × π × 0.25) was higher for mini-PNL (6.69 cm2 vs 14.14; p=0.003). The operative time was longer for mini-PNL (120 vs 162.5 min, p = 0.03). Only one case (5%) required transfusion in NLP 24/26F. Mini-PCNL was associated with tubeless technique (55%) (p = 0.022), which explains lower 24 h postoperative pain, after surgery, measured by VAS (p =0.0004). The hospital stay was equivalent (median: 2 days; p=0.8). Both techniques showed efficacy (SFR at 3 months 80%). There were no statistically significant differences between the number and severity of complications between groups (Group A: 15%, 66.7% Clavien II, Group B: 15%; 66.7% Clavien II, p = 1). CONCLUSIONS: Mini-NLP can manage kidney stones and even large staghorn calculi without nephrostomy in a high percentage of patients. The technical evolution towards a small caliber approach maintains the effectiveness of the procedure without impacting its safety, with benefits perceived by patients such as less postoperative pain.