PARP Inhibitors: A New Horizon for Patients with Prostate Cancer.

The introduction of PARP inhibitors (PARPi) in prostate cancer is a milestone and provides a pathway to hope in fighting this disease. It is the first time that drugs, based on the concept of synthetic lethality, have been approved for prostate cancer. In addition, it is also the first time that genetic mutation tests have been included in the therapeutic algorithm of this disease, representing a significant step forward for precision and personalized treatment of prostate cancer. The objectives of this review are: (1) understanding the mechanism of action of PARPi in monotherapy and combinations; (2) gaining insights on patient selection for PARPi; (3) exposing the pivotal studies that have allowed its approval, and; (4) offering an overview of the ongoing trials. Nevertheless, many unsolved questions remain, such as the number of patients who could potentially benefit from PARPi, whether to use PARPi in monotherapy or in combination, and when is the best time to use them in advanced or localized disease. To answer these and other questions, many clinical trials are underway. Some of them have recently demonstrated promising results that may favor the introduction of new combinations in metastatic castration-resistant prostate cancer.

Safety and outcomes of new generation hormone-therapy in elderly chemotherapy-naive metastatic castration-resistant prostate cancer patients in the real world.

BACKGROUND: Abiraterone acetate and enzalutamide are standard treatments for chemotherapy-naive metastatic castration-resistant prostate cancer (CN-mCRPC). The purpose of this study was to evaluate the effectiveness and safety of these medications in elderly (≥ 75 years old) compared with young CN-mCRPC patients in a real-world clinical setting. Secondarily, we explored the survival prognostic value of different anatomo-clinical factors in elderly group. METHODS: In this retrospective observational multicentre study, we included 134 consecutive CN-mCRPC patients, 64 young and 70 elderly men, who had received AA or Enz. RESULTS: We did not find significant differences in treatment duration [16.6 months, (95% CI 9-24.2 months) vs. 16.8 months (95% CI: 6.3-27.2 months); p = 0.926] and overall survival [median not reached vs. 23.3 months (95% CI 10.2-36.3 months); p = 0.131] between the young and elderly groups. In elderly group, the only predictors of overall survival with AA or Enz were good ECOG performance status and high G8 score. Adverse events of grade ≥3 was similar in elderly group (12.9%) and in the young group (15.6%). Treatment was discontinued due to AEs in 6.3% of young group and 18.6% of elderly group. CONCLUSIONS: Effectiveness and safety of treatment of CN-mRCPC with Abiraterone acetate and enzalutamide were similar in older and younger patients, although treatment discontinuation due to AEs was more frequent in the older age group. In addition to ECOG PS, assessment using specific geriatric scales as G8 screening tool could help to identify patients aged ≥75 who would most benefit from treatment with new-generation hormone therapy.

Single nucleotide polymorphisms as prognostic and predictive biomarkers in renal cell carcinoma.

Despite major advances in the knowledge of the molecular basis of renal cell carcinoma, prognosis is still defined using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. With these premises, we aimed to analyse the expression and to determine the prognostic and predictive value of 64 key single nucleotide polymorphisms in 18 genes related with angiogenesis or metabolism of antiangiogenics in two cohorts of patients with localized and advanced renal cell cancer treated at our institution. The presence of the selected single nucleotide polymorphisms was correlated with clinical features, disease free survival, overall survival and response rate. In patients with localized renal cell cancer, 5 of these polymorphisms in 3 genes involved in angiogenesis predicted for worse disease free survival (VEGFR2: rs10013228; PDGFRA: rs2228230) or shorter overall survival (VEGFR2: rs10013228; VEGFR3: rs6877011, rs307826) (p < 0.05). Rs2071559 in VEGFR2 showed a protective effect (p = 0.01). In the advanced setting, 5 SNPs determined inferior overall survival (IL8: rs2227543, PRKAR1B: rs9800958, PDGFRB: rs2302273; p = 0.05) or worse response rate (VEGFA: rs699947, rs3025010 p ≤ 0.01)). Additionally 1 single nucleotide polymorphism in VEGFB predicted for better response rate rs594942 (p = 0.03). Genetic analysis of renal cell carcinoma patients might provide valuable prognostic/predictive information. A set of SNPs in genes critical to angiogenesis and metabolism of antiangiogenics drugs seem to determine post-surgical outcomes and treatment response in our series.

Mycotic pseudoaneurysm following a kidney transplant: a case report and review of the literature.

Vascular complications represent a significant cause of morbidity and mortality following a kidney transplant. Pseudoaneurysms are rare, occurring in approximately 1% of cases. We present a 15-yr-old patient who received a kidney transplant in the right iliac fossa. Thirty-six days following the transplant, the patient was admitted to the hospital because of a marked increase in serum creatinine levels, arterial hypertension, scrotal edema, and lower right limb pain. The patient did not present fever or raised inflammatory markers. A pseudoaneurysm was diagnosed by means of a Doppler echography and a CT. By a selective arteriography of the right iliac artery, we placed a 8 x 5 cm stent to isolate the pseudoaneurysm, due to the high risk of an extensive defect occurring in the arterial wall. Forty-eight h later the patient underwent transplant nephrectomy. Seven days following surgery, the patient experienced febrile syndrome and therefore another CT was carried out which showed a large abscess around the stent. So we decided to perform another intervention in order to drain this abscess. Due to the extensive loss of the arterial wall where the prosthesis was largely exposed, we ligated the common iliac and external iliac arteries, removed the prosthesis and performed a femoro-femoral bypass with the usual subcutaneous positioning of the prosthesis (separate from surgical site). The stent and mural thrombus were sent for culture analysis and Candida albicans was observed. The diagnosis of a pseudoaneurysm in these types of patients continues to be considered as a surgical emergency by the majority of authors. Transplantectomy is the most frequently used treatment technique. Positioning a stent prior to transplantectomy avoids ligature of the iliac artery in the majority of cases.