Project description:BackgroundOvertreatment is a well-known clinical challenge in local prostate cancer (PCa). Although risk assessment models have contributed to a better stratification of patients with local PCa, a tailored management is still in its infancy. Over the last few decades, microRNAs (miRNAs) have shown promising results as biomarkers in PCa. The aim of this study was to investigate circulating miRNAs after management of local PCa.MethodsThe relative expression of four miRNAs (miRNA-21, -93, -125b, and miRNA-221) was assessed in plasma from 149 newly diagnosed patients with local or locally advanced PCa. Real-time polymerase chain reaction was used for analysis. A baseline sample at time of diagnosis and a follow-up sample after 6 months were assessed. The patients were grouped in an interventional cohort (radical prostatectomy, curative intent radiotherapy, or androgen-deprivation therapy alone) and an observational cohort (watchful waiting or active surveillance).ResultsIn the interventional cohort, levels of both miRNA-93 and miRNA-221 were significantly lower in the follow-up samples compared to baseline z = -2.738, P = 0.006, and z = -4.498, P < 0.001, respectively. The same observation was recorded for miRNA-125b in the observational cohort (z = -2.656, P = 0.008). Both miRNA-125b and miRNA-221 were correlated with risk assessment r = 0.23, P = 0.015, and r = 0.203, P = 0.016 respectively, while miRNA-93 showed tendency to significant correlation with the prostatectomy Gleason score (r = 0.276, P = 0.0576).ConclusionsThe current results indicate a possible role of miRNA-93 and miRNA-221 in disease monitoring in localized and locally advanced PCa. Larger studies are warranted to assess the clinical impact of these biomarkers.
Project description:Background: The study aimed to assess predictors and to identify patients at increased risk of prostate-cancer-specific mortality (CSM) after radical prostatectomy (RP). Methods: A total of 2421 men with localized and locally advanced PCa who underwent RP in 2001−2017 were included in the study. CSM predictors were assessed using multivariate competing risk analysis. Death from other causes was considered a competing event. Cumulative CSM and other-cause mortality (OCM) were calculated in various combinations of predictors. Results: During the median 8 years (interquartile range 4.4−11.7) follow-up, 56 (2.3%) of registered deaths were due to PCa. Cumulative 10 years CSM and OCM was 3.6% (95% CI 2.7−4.7) and 15.9% (95% CI 14.2−17.9), respectively. The strongest predictors of CSM were Grade Group 5 (GG5) (hazard ratio (HR) 19.9, p < 0.0001), lymph node invasion (HR 3.4, p = 0.001), stage pT3b-4 (HR 3.1, p = 0.009), and age (HR 1.1, p = 0.0007). In groups created regarding age, stage, and GG, cumulative 10 years CSM ranged from 0.4−84.9%, whereas OCM varied from 0−43.2%. Conclusions: CSM after RP is related to GGs, pathological stage, age, and combinations of these factors, whereas other-cause mortality is only associated with age. Created CSM and OCM plots can help clinicians identify patients with the most aggressive PCa who could benefit from more intensive or novel multimodal treatment strategies.
Project description:Objective:To assess the feasibility of single-port transperitoneal robotic-assisted laparoscopic radical prostatectomy (spRALP) and discuss its surgical technique. Methods:A 60-year-old male was admitted with an elevated prostate-specific antigen (PSA) level of 13.89 ng/mL and confirmed with prostate cancer on biopsy showing three of 22 positive cores with a Gleason score of 3 + 4 = 7. Multiparametric magnetic resonance (MR) and bone scintigraphy showed organ-confined disease. spRALP was performed using da Vinci Si HD surgical system, with access of a quadri-channel laparoscopic port placed supraumbilically. Two drainage tubes were placed before wound closure. The surgical procedure was largely in consistence with a conventional robotic-assisted laparoscopic radical prostatectomy. Results:The surgery was successfully carried out with a duration of 152 min and an estimated blood loss of 100 mL. The patient was discharged on postoperative Day 4 after removal of both pelvic drainage tubes. Foley catheter was removed on postoperative Day 14. No major complications were encountered. Postoperative pathology showed a Gleason score of 3 + 4 = 7 with no extraprostatic extension and negative surgical margins. Conclusion:Single-port robotic prostatectomy is feasible using the currently available robotic instruments in most Chinese robotic urological centers. Meticulous preoperative planning and careful patient selection are mandatory. Further studies concerning perioperative complications and pentafecta outcome compared with the conventional multi-port robotic prostatectomy is required.
Project description:BACKGROUND:Retzius-sparing robot-assisted laparoscopic radical prostatectomy (rsRARP) allows entire prostatectomy procedure via the pouch of Douglas. In low- and intermediate-risk prostate cancer (PCa) there is level 1 evidence that the Retzius-sparing approach impacts early continence recovery. Since specific data on aggressive and locally advanced cancer is lacking and avoiding rsRARP is presently suggested, we investigated urinary and sexual recovery, perioperative complications and early oncologic outcomes after rsRARP in this particular cohort. METHODS:Prospectively collected data of 50 consecutive men (median age 66?years) with high-risk PCa who underwent rsRARP in a single institution was analysed retrospectively. The follow-up for all patients was 12?months after surgery. RESULTS:3 vs. 12?months after surgery, 82% vs. 98% of men used no pad or one safety pad and 50% vs. 72% used no pad. 89% of patients did not observe a decline of continence if postoperative radiotherapy was carried out. Considering the 17 preoperatively potent patients who underwent bi- or unilateral nerve-sparing surgery, 41% reported their first sexual intercourse within 1?year after rsRARP. 84% of patients had ?pT3a disease and 42% positive surgical margins. A lymphadenectomy was done in 94% of patients with a median lymph node removal of 15 and lymph node metastasis in 13%. 34% underwent adjuvant radiotherapy and 22% adjuvant androgen deprivation therapy (ADT). 1-year recurrence-free survival was 96%, including 25% of patients on adjuvant or salvage ADT. CONCLUSIONS:RsRARP in high-risk PCa is feasible and results in excellent continence rates, even after postoperative radiotherapy. The potency rates are promising but need further clarification in larger cohorts. Reliable oncologic outcomes require longterm follow-up and are awaited.
Project description:More emerging evidence showed that homologous recombination (HR) defect (HRD) may predict sensitivity to platinum agents in metastatic prostate cancer (PCa). Platinum-based neoadjuvant chemotherapy for PCa with HRD has not been reported. Here, we reported a man diagnosed as locally advanced PCa with high Gleason Score (5 + 5) and low PSA level (5.2 ng/ml). Next-generation sequencing (NGS) demonstrated HRD. He received six cycles of platinum-based neoadjuvant chemotherapy before radical prostatectomy (RP). Fifteen months after RP, his PSA level was still undetectable, and no imaging progression was found, indicating a potential role for platinum-based neoadjuvant chemotherapy in locally advanced PCa with HRD.
Project description:The aim of this study was to investigate the prognostic significance of patient age with respect to tumour aggressiveness in men who underwent radical prostatectomy (RP) for prostate cancer. In this study, we reviewed the records of 743 patients who received RP without neoadjuvant or adjuvant therapy at our institution and were followed up for >2 years postoperatively. For our analyses, the patients were divided into two groups according to age: younger (<60 years) and older (≥60 years). Through uni- and multivariate analyses, associations of various clinicopathological parameters, including biochemical recurrence-free survival, with patient age, were evaluated among all patients, and the patients were stratified according to their D'Amico risk classification. Among all subjects, younger (n=126) and older (n=617) patients showed no significant differences regarding pathological parameters and biochemical recurrence-free survival (P=0.288). For the high-risk group (n=206), younger patients had a lower rate of biochemical recurrence-free survival following surgery than older patients (P=0.017), despite the fact that no significant differences were observed regarding various known prognostic parameters between the two age groups. In addition, multivariate analysis revealed that age was an independent predictor of biochemical recurrence-free survival among the high-risk group (P=0.003). Our results showed that relatively younger patients have a comparable biochemical outcome compared with their older counterparts following RP performed for prostate cancer. However, among patients with high-risk disease, younger patients have a worse biochemical outcome following RP compared with older patients.
Project description:For patients with low-risk prostate cancer (PCa), active surveillance (AS) may produce oncologic outcomes comparable to those achieved with radical prostatectomy (RP). Health-related quality-of-life (HRQoL) outcomes are important to consider, yet few studies have examined HRQoL among patients with PCa who were managed with AS. In this study, the authors compared longitudinal HRQoL in a prospective, racially diverse, and contemporary cohort of patients who underwent RP or AS for low-risk PCa.Beginning in 2007, HRQoL data from validated questionnaires (the Expanded Prostate Cancer Index Composite and the 36-item RAND Medical Outcomes Study short-form survey) were collected by the Center for Prostate Disease Research in a multicenter national database. Patients aged ?75 years who were diagnosed with low-risk PCa and elected RP or AS for initial disease management were followed for 3 years. Mean scores were estimated using generalized estimating equations adjusting for baseline HRQoL, demographic characteristics, and clinical patient characteristics.Of the patients with low-risk PCa, 228 underwent RP, and 77 underwent AS. Multivariable analysis revealed that patients in the RP group had significantly worse sexual function, sexual bother, and urinary function at all time points compared with patients in the AS group. Differences in mental health between groups were below the threshold for clinical significance at 1 year.In this study, no differences in mental health outcomes were observed, but urinary and sexual HRQoL were worse for patients who underwent RP compared with those who underwent AS for up to 3 years. These data offer support for the management of low-risk PCa with AS as a means for postponing the morbidity associated with RP without concomitant declines in mental health.
Project description:Currently, the standard management for locally advanced prostate cancer (PCa) is still controversial. In our study, we aimed to compare the survival outcomes of radical prostatectomy (RP) versus external beam radiotherapy (EBRT).We conducted analyses with a large cohort of 38,544 patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016). Propensity score matching, Kaplan-Meier method, and Cox proportional hazard regression were used to reduce the influence of bias and compare the overall survival (OS) and cancer specific survival (CSS). Several different sensitivity analyses including inverse probability of treatment weighting and standardized mortality ratio weighting were used to verify the robustness of the results.Totally, 33,388 men received RP and 5,156 men received EBRT with cT3-4N0M0 PCa were included in this study. According to the Kaplan-Meier curves, RP performed better in both OS and CSS compared with EBRT (P < .0001). In the adjusted multivariate Cox regression, RP also showed better OS and CSS benefits (OS: HR=0.50; 95% confidence interval [CI]: 0.46-0.54; P < .0001 and CSS: HR=0.43; 95% CI: 0.38-0.49; P < .0001). After propensity score matching, RP is still the management that can bring more survival benefits to patients. (OS: HR=0.46; 95% CI: 0.41-0.51; P < .0001 and CSS: HR = 0.41; 95% CI: 0.34-0.48; P < .0001).Our research demonstrated the significantly better survival benefits of RP over EBRT in patients with locally advanced PCa. The results of this study will provide more evidence to help clinicians choose appropriate treatment strategies.
Project description:PurposeMen with high-risk features (extraprostatic extension or high Gleason grade) face a high risk of prostate cancer recurrence after radical prostatectomy. Clinical trials of adjuvant systemic therapy for such patients have been limited.Patients and methodsThe SWOG (Southwest Oncology Group) S9921 study randomly assigned 983 men with high-risk features at prostatectomy to receive adjuvant therapy with androgen deprivation (ADT) alone or in combination with mitoxantrone chemotherapy. ADT consisted of goserelin and bicalutamide for 2 years.ResultsAlthough the final primary treatment comparison results are not ready for publication, this article reports results in the ADT-alone control arm with a median follow-up of 4.4 years. For these 481 men, the estimated 5-year biochemical failure-free survival is 92.5% (95% CI, 90 to 95), and 5-year overall survival is 95.9% (95% CI, 93.9 to 97.9).ConclusionThe results of this trial, taken in context, make a compelling argument for counseling all high-risk patients with prostate cancer about adjuvant ADT. This article discusses the challenges in the design and implementation of clinical trials to take the next step forward in adjuvant therapy for prostate cancer because of the excellent survival achieved with currently available therapies and highlights the need for better molecular markers to personalize care.
Project description:While radical prostatectomy (RP) plays a prominent role in the management of localized prostate cancer, its role in high risk or metastatic disease is less clear. Due to changes in prostate cancer screening patterns, particularly those made by the United States Preventive Services Task Force, data is suggesting increasing incidences of high risk and metastatic disease, underlying the importance of continued research in this area. While past approaches to management may have discouraged surgical intervention, more contemporary approaches have attempted to evaluate its effectiveness and utility. The purpose of this review is an updated discussion of the current literature regarding surgical approaches to high risk prostate cancer. The PubMed and Medline databases were queried for English language articles related to the surgical management of high-risk prostate adenocarcinoma. In this review, we examine the utility of surgery as a single or multimodal approach to management with patients with high risk, locally advanced, and metastatic prostate cancer. Outcomes measures are reviewed including data on survival and recurrence rates. Functional outcomes are an important consideration in prostate cancer management and while data is more limited, this review examines some of the key findings. Finally, a discussion regarding surgical complication rates and ongoing clinical trials is addressed. While surgery appears to be promising in this patient cohort, there remains significant heterogeneity in the data that ongoing trials may be able to address. At its current level of understanding, surgery should be considered as a potential tool in patient management, but may play a more prominent role in a multi-modality setting for optimal outcomes.