Prognostic value of germline mutations in metastatic hormone-sensitive prostate cancer (mHSPC).

BACKGROUND: About 8% to 12% of patients presenting with mHSPC exhibit germline pathogenic variants (PV) in cancer predisposition genes. The aim of this study is to assess the presence of germline PV as a prognostic factor in the setting of mHSPC and to determine whether mutational status can predict rapid progression to castration resistance. METHODS: Genetic analysis using a multigene next-generation sequencing (NGS) panel was performed on 34 patients diagnosed with mHSPC undergoing treatment. We assessed the prevalence of germline PV and examined differences based on clinical-pathological characteristics, family history (FH), prostate-specific antigen (PSA) response, impact on time to castration-resistant prostate cancer (TTCRPC), and overall survival (OS). RESULTS: Germline PV were identified in 6 patients (17,6%). When comparing the clinical-pathological characteristics of PV carriers (n = 6) to noncarriers (n = 28), no significant associations were observed except for the presence of FH of hereditary breast and ovarian cancer (HBOC) syndrome and/or Lynch syndrome (P = 0.024). At a median follow-up of 33 months, significant differences in OS were observed based on the presence of PV (26 months in carriers vs. 74 months in noncarriers; P < 0.01). Patients who harbored a BRCA2 mutation (n = 3) showed a worse clinical outcome, presenting a shorter TTCRPC (7 months vs. 23 months; P = 0.005) and lower OS (7 months vs. 74 months; P < 0.001) compared to noncarriers (n = 31). CONCLUSION: mHSPC germline PV carriers had a worse survival outcome. Furthermore, BRCA2 germline mutation was an independent poor prognostic factor for mHSPC disease, associated with earlier progression to castration-resistant prostate cancer, and shorter OS. These results highlight the importance of evaluating germline mutational status in patients with hormone-sensitive prostate cancer.

En Bloc enucleation with early apical release technique using MOSES (En Bloc MoLEP) vs. classic En Bloc HoLEP: a single arm study comparing intra- and postoperative outcomes.

BACKGROUND AND PURPOSE: We aimed to describe the technique and outcomes of En-Bloc MOSES laser enucleation of the prostate (En-Bloc MoLEP) with early apical release comparing it to En-Bloc HoLEP (non-MOSES). PATIENTS AND METHODS: This is a single-arm prospective study, using a historical control. n = 80 patients were enrolled to the En Bloc MoLEP group and compared to a retrospective group of n = 137 patients treated by En Bloc HoLEP (non-MOSES), in total n = 217 patients. RESULTS: En-Bloc MoLEP, showed to significantly improve the surgical time by 32% compared to non-MOSES HoLEP (32.16 ± 14.46 min, 47.58 ± 21.32, respectively; P = 0.003). Enucleation time, ablation rate and hemostasis time were also significantly improved (P < 0.001, for all three parameters). Enucleation time was 22.10 ± 9.27 min and 31.46 ± 14.85 min (P < 0.001), ablation rate 4.11 ± 2.41 and 2.54 ± 1.31 gr/min (P < 0.001), Hemostasis time 3.01 ± 2.50 and 8.35 ± 5.38 min (P < 0.001), for En Bloc MoLEP and En Bloc HoLEP, respectively. Q-max, PVR, PSA and IPSS showed significant improvement, however, at 12 months no significant differences were observed comparing both groups. CONCLUSIONS: En-Bloc MoLEP was significantly better than En-Bloc HoLEP in terms of surgical time, enucleation time, ablation rate and hemostasis time. However, large comparative RCT with long-term follow-up are needed.

Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain.

(1) Background: Intravesical mitomycin-C (MMC) combined with hyperthermia is increasingly used in non-muscle invasive bladder cancer (NMIBC), especially in the context of a relative BCG shortage. We aim to determine real-world data on the long-term treatment outcomes of adjunct hyperthermic intravesical chemotherapy (HIVEC) with MMC and a COMBAT® bladder recirculation system (BRS); (2) Methods: A prospective observational trial was performed on patients with NMIBC treated with HIVEC using BRS in nine academic institutions in Spain between 2012-2020 (HIVEC-E). Treatment effectiveness (recurrence, progression and overall mortality) was evaluated in patients treated with HIVEC MMC 40mg in the adjuvant setting, with baseline data and a clinical follow-up, that comprise the Full Analysis Set (FAS). Safety, according to the number and severity of adverse effects (AEs), was evaluated in the safety (SAF) population, composed by patients with at least one adjunct HIVEC MMC instillation; (3) Results: The FAS population (n = 502) received a median number of 8.78 ± 3.28 (range 1-20) HIVEC MMC instillations. The median follow-up duration was 24.5 ± 16.5 (range 1-81) months. Its distribution, based on EAU risk stratification, was 297 (59.2%) for intermediate and 205 (40.8%) for high-risk. The figures for five-year recurrence-free and progression-free survival were 50.37% (53.3% for intermediate and 47.14% for high-risk) and 89.83% (94.02% for intermediate and 84.23% for high-risk), respectively. A multivariate analysis identified recurrent tumors (HR 1.83), the duration of adjuvant HIVEC therapy <4 months (HR 1.72) and that high-risk group (HR 1.47) were at an increased risk of recurrence. Independent factors of progression were high-risk (HR 3.89), recurrent tumors (HR 3.32) and the induction of HIVEC therapy without maintenance (HR 2.37). The overall survival was determined by patient age at diagnosis (HR 3.36) and the treatment duration (HR 1.82). The SAF population (n = 592) revealed 406 (68.58%) patients without AEs and 186 (31.42%) with at least one AE: 170 (28.72%) of grade 1-2 and 16 (2.7%) of grade 3-4. The most frequent AEs were dysuria (10%), pain (7.1%), urgency (5.7%), skin rash (4.9%), spasms (3.7%) and hematuria (3.6%); (4) Conclusions: HIVEC using BRS is efficacious and well tolerated. A longer treatment duration, its use in naïve patients and the intermediate-risk disease are independent determinants of success. Furthermore, a monthly maintenance of adjunct MMC HIVEC diminishes the progression rate of NMIBC.

'En Bloc' HoLEP with early apical release in men with benign prostatic hyperplasia.

PURPOSE: HoLEP represents an excellent treatment option for benign prostatic hyperplasia. Recently, 'en bloc' techniques resulting in improved visualization, shorter surgical times, and easier recognition of the dissection plane have been described. In this paper we describe the 'En bloc' HoLEP technique with early apical release. MATERIALS AND METHODS: Between January 2015 and March 2017, 137 consecutive patients were subjected to this technique by a single surgeon. The following parameters were measured pre- and post-procedure: International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual urine (PVR) and PSA. Complications were recorded. RESULTS: Mean (SD; range) age was 66 years (8.0; 51-84), mean PSA was 4.8 ng/ml (7.0; 0.3-70), mean prostate volume was 75.63 ml (42.1; 37-253), mean volume of prostatic tissue removed was 65.9 ml (35.8; 30-217). Mean surgical duration was 47.58 min (21.3; 15-120 min): enucleation 31.5 min (14.9; 5-80 min), morcellating 6.9 min (6.6; 1-60 min). Mean hospitalization duration was 1.2 days (range 1-3), mean catheterization time was 1.2 days (range 1-5). The rate of stress urinary incontinence (SUI) was 5.8, 1.5 and 0.7% at 1, 3, and 6 months post-operation, respectively. Compared to pre-operative values, IPSS, Qmax, and PVR showed significant improvements at 1, 3, 6, and 12 months following the operation (p < 0.05). CONCLUSIONS: 'En Bloc' HoLEP with early apical release is a safe technique that allows for easier recognition of the surgical plane and preserves the external sphincter's mucosa to provide low rates of post-operative stress incontinence and significant functional results.