Prostate Cancer and Prostatic Diseases最新文献

Objective: We sought to determine, in a prospective long term cohort, the prognostic value of negative MR imaging with respect to upgrading and need for intervention in men on AS.

Method: A long term prospective single centre study of men on Active surveillance with MR imaging. Primary outcome was upgrading on biopsy and rate of intervention. After incorporation of MRI into the AS protocol in 2013, men with negative imaging underwent systematic biopsy only for cause.

Results: Five hundred and thirty AS patients had one or more MRI, with median follow-up of 8.5 years. At baseline, 39 patients (7.4%) had negative MRIs 161 (30%) equivocal, and 330 (62%) had a positive MRI. Two hundred and twenty-nine patients were upgraded; 5% with invisible lesions, 34% with PiRADS 3, and 52% with PiRADS 4-5. Two hundred and twenty-nine (43%) of the 530 men were eventually treated. No patient with a negative PiRADS was treated, vs 36% with PiRADS 3 and 52% with PiRADS 4-5 (p < 0.001). In 331 men with serial MRIs, upgrading occurred in 46% of men with stable or improved MRI, and 57% in those with MRI progression. In the 70 patients whose MRI improved from PiRADS 4-5 to 3, 46% were upgraded. No patients who transitioned from PiRADS 3-5 to 1-2 were upgraded. Time to grade progression was highly inversely correlated with PIRADS score.

Conclusion: MRI invisible cancers demonstrated dramatically reduced rates of progression and no patient required intervention. Despite the absence of routine biopsies in the MR negative group, none of these patients progressed over time to GG ≥ 3 or metastatic disease. This suggests that, in men on active surveillance, image guided management, restricting biopsies to targeted biopsies of regions of interest, is sufficient to identify clinically significant cancers.

Background: Patients treated with RT and long-term androgen deprivation therapy (ltADT) for high-risk localized prostate cancer (HRLPC) with 1 high-risk factor (any of Gleason ≥8, PSA > 20 ng/mL, ≥cT3; "high-risk") have better outcomes than those with 2-3 factors and/or cN1 disease ("very high risk"). We evaluated whether this risk stratification could determine benefit from ltADT versus short-term (stADT).

Methods: The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) repository of randomized trials was queried to identify eligible patients and trials. The key outcomes of interest were metastasis-free survival (MFS), overall survival (OS), time to metastasis (TTM) and prostate cancer-specific mortality (PCSM). Stratified Cox and Gray's regression were used to obtain the overall treatment effect for outcomes and risk groups, and the Wald interaction test to estimate whether treatment benefit differed by risk group or trial. Heterogeneity of studies was assessed by Cochran's Q and I².

Results: 2780 patients from 3 trials were included. Patients with very-high risk disease had greater benefit with ltADT compared to high-risk disease (MFS HR 0.77 [0.68-0.88] vs. 0.89 [0.76-1.03]; TTM 0.61 [0.51-0.74] vs. 0.77 [0.59-0.99]; PCSM 0.71 [0.56-0.90] vs. 0.82 [0.59-1.14]; OS 0.87 [0.76-1.00] vs. 0.93 [0.79-1.08]), but there was no statistically significant difference in treatment effect by risk group (p-interaction >0.1). Heterogeneity for treatment effect across trials was low in the very high-risk group and moderate in the high-risk group.

Conclusions: Clinical risk stratification merits further evaluation in clinical trials to identify which patients with HRLPC may benefit from ltADT versus stADT.

Background: Despite the relatively low infection rate following transperineal prostate biopsy (TPB), it remains unresolved whether periprocedural antibiotic prophylaxis (PAP) can be omitted. Our aim was to compare infectious complications (genitourinary infections/GUI, fever, sepsis, readmission rate, 30-day-mortality) following TPB, considering all studies of varying levels of evidence that enable a direct comparison between patients with and without PAP.

Methods: We performed a comprehensive search in PubMed/Medline, Embase, Web of Science, and Cochrane databases, as well as grey literature sources, to identify reports published until January 2024. All studies comparing the incidence of infectious endpoints following TPB with vs. without PAP were included in the analyses. The GRADE approach was employed to assess the certainty of evidence for each comparison.

Results: Twenty-three studies met the inclusion criteria involving 6520 and 5804 patients who underwent TPB with vs. without PAP, respectively. Two of the 23 studies were randomized-controlled trials, not all studies investigated all endpoints. Pooled incidences between patients with vs. without PAP for the endpoints GUI (0.50% vs. 0.37%), fever (0.44% vs. 0.26%), sepsis (0.16% vs. 0.13%), and readmission rate (0.35% vs. 0.29%) showed no significant differences (all p > 0.250). The corresponding odds ratios (including 95% confidence interval) also revealed no statistically significant differences: 1.37 (0.74-2.54) [GUI], 0.87 (0.28-2.66) [fever], 1.30 (0.46-3.67) [sepsis], and 1.45 (0.70-3.03) [readmission rate]. No study reported events regarding 30-day-mortality. In subgroup analyses and sensitivity analyses, TPB without PAP showed no significantly higher complication rates regarding all analyzed endpoints.

Conclusions: Infectious complications after TPB occur very rarely and cannot be further reduced by PAP. Considering the results of this systematic review and adhering to the principles of effective antibiotic stewardship, omitting PAP in the context of TPB is advisable.

Background: Metastatic prostate cancer (PCa) has much lower survival and ultimately develops castration resistance, which expects novel targets and therapeutic approaches. As a result of iron-dependent lipid peroxidation, ferroptosis triggers programmed cell death and has been associated with castration-resistant prostate cancer (CRPC).

Subjects: To better understand how ferroptosis can be used to treat CRPC, we reviewed the following: First, ferroptosis mechanisms and characteristics. We then pay attention to ferroptosis effects on CRPC, and the relationship between ferroptosis and CRPC treatment. Finally, we'd like to figure out if ferroptosis could predict the prognosis of CRPC thus screening early for populations that may benefit from appropriate therapies.

Results: The review demonstrated that ferroptosis regulators like PI3K/AKT/mTOR, DECR1 et al., have a significant role in the development of CRPC and that several inducers of ferroptosis, such as erastin, BSO, RSL3, and FIN56, have already demonstrated their effects in that area. What's more, ferroptosis is crucial for radiation-induced anticancer effects by inducing lipid peroxidation and regulating p53, AMPK, and others. Additionally, it has been discovered that certain GPX4 and SLC7A11 inhibitors can increase radiosensitivity, which brings new combination strategies. Finally, among the genes associated with ferroptosis, which may be excellent predictors of prostate cancer prognosis, several risk models have been developed and shown promising predictive capabilities.

Conclusions: Ferroptosis can serve as a potential therapeutic target for CRPC, and could be a new strategy for combination therapy. Moreover, ferroptosis-related genes may be great indicators of PCa prognosis. Further research on ferroptosis in CRPC therapy can benefit from the frameworks provided by this review.

Background: Stereotactic body radiotherapy (SBRT) is pivotal in managing radio-recurrent prostate cancer (PCa). This study aims to comprehensively review its efficacy and associated severe toxicities.

Methods: A thorough review of PubMed and EMBASE databases up to July 2024 was conducted to assess recurrence-free survival (RFS) with salvage SBRT across various subgroups. Survival curves were reconstructed using WebPlotDigitizer and a newly developed shiny application.

Results: Thirty-six studies were analyzed, with 15 papers (682 patients) contributing to survival curve reconstruction. Median RFS was 36.2 months, with 2-, 3-, and 5-year rates of 64.8%, 50.7%, and 40.6%, respectively. Factors associated with improved RFS included whole-gland irradiation [focal vs. whole, hazard ratio (HR) 1.83 (95% CI: 1.16-2.87), p = 0.008], and higher biologically effective dose (BED) [120-138.1 Gy vs. 144-167.7 Gy, HR 1.40 (95% CI: 1.07-1.83), p = 0.015]. Severe (grade ≥ 3) acute and late genitourinary (GU) toxicities occurred in 1.4% (95% CI: 0.8-2.3) and 3.7% (95% CI: 2.6-4.9) of patients, respectively. Severe acute and late gastrointestinal (GI) toxicities were reported in 0.5% (95% CI: 0.2-1.1) and 0.4% (95% CI: 0.1-1.0) of patients, respectively. Combined severe GU and GI toxicities were observed in 5.8% (95% CI: 4.5-7.4) and 1.3% (95% CI: 0.7-2.2) of patients, respectively.

Conclusions: This study provides a comprehensive assessment of toxicities and conducts a pooled analysis of RFS for salvage SBRT in radio-recurrent PCa. Factors such as whole-gland irradiation, and higher BED show promise as prognostic indicators for RFS. However, confirmation through randomized controlled trials is essential due to the low levels of evidence and study heterogeneity.

Background: Androgen receptor pathway inhibitors (apalutamide [APA], enzalutamide [ENZ], abiraterone acetate plus prednisone [AAP]) combined with androgen-deprivation therapy (ADT) are effective life-prolonging treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the impact of upfront therapy for mHSPC on outcomes in real-world clinical practice in the United States.

Methods: This retrospective, observational cohort study used electronic healthcare records from the ConcertAI RWD 360 Prostate Cancer Dataset. All patients with newly diagnosed mHSPC from January 2018 to June 2023 were enrolled and followed-up until death, end of follow-up, or January 2024, whichever occurred first. Kaplan-Meier methods were used to estimate overall survival (OS), time to PSA50/PSA90 (50%/90% decline in PSA from baseline, respectively), time to undetectable PSA ( ≤ 0.2 ng/ml), and time to castration resistance (TTCR). Adjusted hazard ratios (aHR) were estimated using inverse probability of treatment weighted multivariate Cox proportional models adjusted for age, comorbidities, BMI, and baseline PSA.

Results: 4937 patients with mHSPC were included in the analysis: 315 received upfront APA + ADT, 1181 ENZ + ADT, 1760 AAP + ADT, 432 docetaxel (DTX) + ADT, and 1249 ADT alone. Percentages of patients reaching PSA50, PSA90, and undetectable PSA at 3 months were significantly higher for APA + ADT (70%/49%/44%, respectively) compared to ENZ + ADT (60%/38%/32%), AAP + ADT (59%/37%/33%) and ADT alone (32%/15%/32%). OS and TTCR were also significantly longer for APA + ADT (66%/77% respectively at 24 months) vs ENZ + ADT (55%/63%) AAP + ADT (59%/67%) and ADT alone (54%/57%). Starting treatment with APA + ADT was associated with a significantly reduced risk of death compared with ENZ + ADT (aHR, 95%CI) (0.66, 0.51-0.87), AAP + ADT (0.72, 0.55-0.94), and ADT alone (0.64, 0.49-0.84).

Conclusions: Numerous patients were not treated with intensified therapies despite their increased effectiveness. First-line APA + ADT in mHSPC was associated with statistically significantly longer OS, longer TTCR, and faster and deeper PSA responses than other life-prolonging treatments in real-world clinical practice in the US.

Background: Prostate biopsy is the most common approach for diagnosing prostate cancer (PCa); however, it has inherent limitations, such as the invasive procedure, postoperative complications, and false negative results. We aimed to provide a noninvasive diagnostic strategy for patients with highly suspected PCa and to evaluate the feasibility of performing biopsy-spared radical prostatectomy.

Methods: This prospective study included a total of 57 patients between November 10, 2022, and December 1, 2023. All 57 patients underwent radical prostatectomy without prior prostate biopsy based on a noninvasive diagnostic strategy consisting of a diagnostic prediction model [comprised of the prostate imaging-reporting and data system (PI-RADS) score and prostate-specific antigen density (PSAD)] and the ¹⁸F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/computed tomography (CT) examination. The primary endpoint was the positive predictive value (PPV) of clinically significant PCa [the International Society of Urological Pathology (ISUP) grade ≥2, Gleason score ≥3 + 4]. The secondary endpoints were a PPV of any-grade PCa (ISUP grade ≥ 1, Gleason score ≥3 + 3) and high-grade PCa (ISUP grade ≥3, Gleason score ≥4 + 3), and the false positive rate of the diagnostic strategy.

Results: Of the 371 screened patients with clinically suspected PCa, 57 patients fulfilled the criteria and consented to participate in this study. The median PSAD level was 0.56 (0.42-0.82) ng/mL²; 13 (22.8%) patients were identified as having a PI-RADS score of 4, and 44 (77.2%) patients with a PI-RADS score of 5. The median SUVmax of ¹⁸F-PSMA-1007 PET/CT was 21.6 (15.8-33.0). For the 57 enrolled patients who received radical prostatectomy directly, the PPV of clinically significant PCa was 98.2% [56/57, 95% confidence interval (CI): 90.6-100%]. Only 1.8% (1/57, 95% CI: 0.0-9.4%) of patients were diagnosed with clinically insignificant PCa (ISUP grade = 1, Gleason score = 3 + 3). The PPV of any-grade PCa and high-grade PCa were 100% and 73.7% (42/57, 95% CI: 60.3-84.5%), respectively. No one had a false positive result.

Conclusions: We proposed a noninvasive diagnostic strategy consisting sequentially of a diagnostic prediction model and the ¹⁸F-PSMA-1007 PET/CT examination for diagnosing PCa. Despite some limitations, our initial findings suggest the potential feasibility of radical prostatectomy without prior prostate biopsy.

Background: Without head-to-head trials between talazoparib+enzalutamide (TALA + ENZA), olaparib+abiraterone acetate (OLAP + AAP), and niraparib plus AAP (NIRA + AAP) the ability to evaluate their relative efficacy as first-line (1 L) treatment in metastatic castration-resistant prostate cancer (mCRPC) is limited. The objective of this study was to assess the relative efficacy between TALA + ENZA (TALAPRO-2) versus OLAP + AAP (PROpel) and NIRA + AAP (MAGNITUDE) in 1 L mCRPC via a matching-adjusted indirect treatment comparison (MAIC).

Methods: Patient-level data from TALAPRO-2 and published data from PROpel and MAGNITUDE were used. TALAPRO-2 data were reweighted to satisfy the eligibility criteria for PROpel and MAGNITUDE. Talazoparib (0.5 mg/day) plus enzalutamide (160 mg/day) was compared to olaparib (300 mg twice daily) plus abiraterone acetate (1000 mg/day) and niraparib (200 mg/day) plus abiraterone acetate (1000 mg/day). Hazard ratios (HRs) were calculated for radiographic progression-free survival (rPFS) and overall survival (OS), and odds ratios (ORs) for prostate-specific antigen (PSA) response and objective response rate (ORR). Additional efficacy outcomes were assessed.

Results: In all-comers, TALA + ENZA was statistically superior to OLAP + AAP for rPFS (HR: 0.727; 95% confidence interval [CI]: 0.565, 0.935) and PSA response (OR: 1.663; 1.101, 2.510), and numerically favored for OS (HR: 0.847; 0.667, 1.076) and ORR (OR: 1.109; 0.646, 1.903). In patients with homologous recombination repair mutations (HRRm), relative to NIRA + AAP, TALA + ENZA was statistically superior for rPFS (HR: 0.460; 0.280, 0.754), and numerically favored for OS (HR: 0.601; 0.347, 1.041) and ORR (OR: 1.524; 0.579, 4.016).

Conclusions: Results suggest that TALA + ENZA may provide improvements in clinical outcomes relative to OLAP + AAP and NIRA + AAP in 1 L mCRPC; however, inherent limitations associated with the complexity of the analyses must be considered.