PURPOSE Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition. METHODS MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641 ) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR−, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR− cohort. RESULTS Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR− cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events. CONCLUSION Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.

No abstract

ВступНирково-клітинний (НКР) рак становить 2-3 % усіх онкологічних захворювань з найбільшою захворюваністю у західних країнах. За останні два десятиліття захворюваність на рак нирки зросла приблизно на 2 %, як у всьому світі, так і в Європі [1].Хірургічне лікування -основний вид терапії пацієнтів з НКР. Сучасною тенденцією в лікуванні пухлин нирок є широке впровадження органозберігаючої хірургії (ОЗХ). Ця тенденція поширюється на складні види новоутворень -великого розміру, з внутрішьновенозним поширенням, інтраперенхімні, а також мультифокальні пухлини нирки.Лікування пацієнтів з мультифокальним нирково-клітинним раком є одним з найбільш складних завдань, оскільки стратегія лікування таких хворих досі остаточно не вирішена, а вибір метода лікування мультифокального раку є джерелом наукових дебатів. При цьому мультифокальність залишається одним із відносних протипоказань до ОЗХ [2].

Surgical correction of the pathology of the middle and lower third of the ureter in most cases is a complex technical problem, especially in the situation of extended iatrogenic defects of this organ. The purpose of the work was to determine the effectiveness of the Boari operation in the correction of ureteral defects and to demonstrate the prognostic factors of this intervention. Material and methods. The study included 81 patients. Their average age was 47.4±12.2 years. Iatrogenic problems prevailed in the whole group (98.8%). Right-sided changes took place in 40 (49.4%) cases, left-sided were diagnosed in 41 (50.6%) cases. Patients with bilateral injuries accounted for 9.9% (8 patients) of the total studied contingent. In accordance with the length of the tubularized vesicular flap, all patients were divided into two groups: Group 1 (short flap) had reconstruction of the lower third of the ureter to the level of its intersection with the iliac vessels (34 / 42.0% of the patient); Group 2 (long flap) had reconstruction of the lower and middle third of the ureter to the level above its intersection with the iliac vessels (47 / 58.0% of the patient). The technique of the performed surgical interventions somewhat differed from the classical Boari operation due to the use of a minimum number of sutures to connect the ureter with the vesicular flap and the absence of fixation of the flap to the psoas muscle. It included the introduction of 250-300 ml of saline into the bladder, mobilization of the apex and lateral surfaces of the bladder. The volume of bladder mobilization depended on the length of the flap. If it was necessary to cut a flap more than 5 cm long, the contralateral and posterior parts of the bladder were isolated. The width of the distal part of the flap was not less than 2.0 cm; the width of the base of the flap was not less than 4.0 cm. In most cases (77 patients – 95.1%), a submucosal tunnel with a length of at least 10 mm was created in the distal part of the flap. The ureter with a stent was passed through the tunnel and fixed to the bladder mucosa using one interrupted suture. After that, the flap was tubularized and fixed to the adventitia of the ureter with four interrupted sutures. In 4 (4.9%) cases, a simple anastomosis was used between the flap and the ureter without the formation of a submucosal tunnel. Kidney mobilization was performed in 32 (39.5%) patients. To reconstruct the ureter to the level of its middle or upper third, an original modification of Boari's operation was used, which consists in forming a flap of optimal length and width due to its multiple transverse incisions. The effectiveness of Boari operation was assessed retrospectively by analyzing complications and long-term results of treatment to predict which univariate logit regression analysis was used in all studied samples. Results and discussion. The length of the bladder flap varied from 4 to 21 cm and averaged 11.2±5.4 cm. The overall incidence of intraoperative complications did not exceed 14.8%. The rate of postoperative complications reached 45.7%, but their gradation, with the exception of one case, corresponded to I or II according to Clavien-Dindo. The total number of positive long-term results (good + satisfactory result) was 88.9%. The complication rate was objectively associated with the presence of a ureteral-vaginal fistula in patients (p <0.049). A significant prognostic value in relation to long-term results of treatment was found only in one factor, i.e. the volume of the bladder less than 350 ml (p <0.039). Conclusion. Boari operation allows to restore not only lower and middle third of the ureter patency, but also to perform total ureteral reconstruction in individual patients with good functional results. A negative factor in the prognosis of complications of this operation is the presence of a ureteral-vaginal fistula, and long-term results – the volume of the bladder is less than 350 ml

No abstract