The impact of biochemical recurrence (BCR) after radical treatment of prostate cancer on oncological outcomes remains unclear. A new European Association of Urology BCR risk stratification (low and ...high risk) has been proposed. To validate these risk groups, we retrospectively analyzed data for 1125 post-radical prostatectomy (RP) BCR patients (surgery between 1992 and 2006). Univariable Kaplan-Meier plots and multivariable Cox regression models with time-dependent covariates were used to test the independent predictor status of the risk grouping on metastatic progression (MP) and prostate cancer-specific mortality (PCSM). The 5-yr MP-free and PCSM-free survival rates were significantly higher among patients with low BCR risk compared to their high-risk counterparts. In multivariable analyses, the BCR risk grouping reached independent predictor status for MP (hazard ratio HR 3.46; p<0.001) and PCSM (HR 5.12; p<0.001). Salvage radiation therapy, especially when delivered at prostate-specific antigen <0.5ng/ml, was highly protective. Our findings corroborate the validity of this novel BCR risk grouping, which is easily applicable in daily practice and could be valuable in decision-making for salvage therapy and clinical trials.
The European Association of Urology grouping for the risk of biochemical recurrence of prostate cancer after radical prostatectomy was valid when applied in a European study cohort.
Our findings corroborate the validity of the novel European Association of Urology biochemical recurrence risk grouping, which is easily applicable in daily practice and could be valuable in decision-making for salvage therapy and clinical trials.
Abstract Context The clinical significance of positive surgical margins (PSMs) in radical prostatectomy (RP) specimens and the management of affected patients remain unclear. Objective To address ...pitfalls in the pathologic interpretation of margin status; provide an update on the incidence, predictors, and long-term oncologic implications of PSMs in the era of robot-assisted laparoscopic RP (RALRP); and suggest a practical evidence-based approach to patient management. Evidence acquisition A systematic review of the literature was performed in April 2013 using Medline/PubMed, Web of Science, and Scopus databases and the Cochrane Database of Systematic Reviews. Studies focusing on PSMs in RP pertinent to the objectives of this review were included. Particular attention was paid to publications within the last 5 yr and those concerning RALRP. Evidence synthesis A total of 74 publications were retrieved. Standardized measures to overcome variability in the pathologic interpretation of surgical margins have recently been established by the International Society of Urological Pathology. The average rate of PSMs in contemporary RALRP series is 15% (range: 6.5–32%), which is higher in men with a more advanced pathologic stage and equivalent to the rate reported in prior open and laparoscopic prostatectomy series. The likelihood of PSMs is strongly influenced by the surgeon's experience irrespective of the surgical approach. Technical modifications using the robotic platform and the role of frozen-section analysis to reduce the margin positivity rate continue to evolve. Positive margins are associated with a twofold increased hazard of biochemical relapse, but their association with more robust clinical end points is controversial. Level 1 evidence suggests that adjuvant radiation therapy (RT) may favorably affect prostate-specific antigen recurrence rates, but whether the therapy also affects systemic progression, prostate cancer–specific mortality, and overall survival remains debatable. Conclusions Although positive margins in prostate cancer are considered an adverse oncologic outcome, their long-term impact on survival is highly variable and largely influenced by other risk modifiers. Adjuvant RT appears to be effective, but further study is required to determine whether early salvage RT is an equivalent alternative.
Prostate cancer (PCa) is among the most commonly diagnosed malignancies in men. Although 5-year survival in patients with localised disease reaches nearly 100%, metastatic disease still remains ...incurable. Therefore, there is a need for markers indicating metastatic dissemination.
EGFR overexpression (EGFR
) was tracked in 1039 primary tumours, circulating tumour cells from 39 d'Amico high-risk patients and metastatic samples from 21 castration-resistant PCa cases. EGFR status was compared to clinical parameters and multiple molecular factors were assessed using immunohistochemistry and gene ontology analysis. The functional aspect of EGFR was evaluated by plating PC-3 cells on soft and rigid matrices.
EGFR
was found in 14% of primary tumours, where it was associated with shorter metastasis-free survival and was an independent indicator of worse overall survival. EGFR
correlated with a pro-migratory and pro-metastatic phenotype of tumour cells as well as rich collagen fibre content. All circulating tumour cells (detected in 13% of cases) were positive for EGFR, independent of their EMT-related phenotype. EGFR
was more prevalent in castration-resistant bone metastases (29% of patients) and supported growth of human PCa cells on rigid matrices mimicking bone stiffness.
EGFR
is a stable, EMT-independent marker of PCa disseminating to rigid organs, preferentially bones.
Persistent prostate-specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP).
To investigate the impact of persistent PSA at 6wk after RP on ...long-term oncologic outcomes and to assess patient characteristics associated with persistent PSA.
Within a high-volume center database we identified patients who harbored persistent (≥0.1ng/ml) versus undetectable PSA (<0.1ng/ml) at 6wk after RP. Patients with neo- and/or adjuvant androgen-deprivation therapy (ADT) were excluded.
Logistic regression models tested for prediction of persistent PSA. Kaplan–Meier analyses and Cox regression models tested the effect of persistent PSA on metastasis-free survival (MFS), overall survival (OS), and cancer-specific survival (CSS) rates. Propensity score matching (PSM) was performed to test the impact of salvage radiotherapy (SRT) on OS and CSS in patients with persistent PSA.
Of 11 604 identified patients, 8.8% (n=1025) harbored persistent PSA. At 15yr after RP, MFS, OS, and CSS were 53.0% versus 93.2% (p<0.001), 64.7% versus 81.2% (p<0.001), and 75.5% versus 96.2% (p<0.001) for persistent versus undetectable PSA, respectively. In multivariable Cox regression models, persistent PSA represented an independent predictor for metastasis (hazard ratio HR: 3.59, p<0.001), death (HR: 1.86, p<0.001), and cancer-specific death (HR: 3.15, p<0.001). SRT was associated with improved OS (HR: 0.37, p=0.02) and CSS (HR: 0.12, p<0.01) after 1:1 PSM. Main limitation is missing data on postoperative PSA and duration of salvage ADT.
Persistent PSA is associated with worse oncologic outcome after RP, namely, metastasis, death, and cancer-specific death. In patients with persistent PSA, SRT resulted in improved OS and CSS.
We assessed the impact of persistent prostate-specific antigen (PSA) at 6wk after radical prostatectomy on oncologic outcomes. Early persistent PSA was associated with worse metastasis-free survival, overall survival, and cancer-specific survival. Salvage radiotherapy may result in a survival benefit in well-selected patients.
Persistent prostate-specific antigen (PSA; ≥0.1ng/ml) at 6wk after radical prostatectomy represents an independent predictor for worse long-term oncological outcome after radical prostatectomy in patients with nonmetastatic prostate cancer. Specifically, persistent PSA is associated with death and development of metastasis. In selected patients, salvage radiotherapy may lead to a survival benefit in patients with persistent PSA.
Abstract Background Although the initial robot-assisted radical prostatectomy (RARP) series showed 12-mo potency rates ranging from 70% to 80%, the few available comparative studies did not permit ...any definitive conclusion about the superiority of this technique when compared with retropubic radical prostatectomy (RRP) and laparoscopic radical prostatectomy (LRP). Objectives The aims of this systematic review were (1) to evaluate the current prevalence and the potential risk factors of erectile dysfunction after RARP, (2) to identify surgical techniques able to improve the rate of potency recovery after RARP, and (3) to perform a cumulative analysis of all available studies comparing RARP versus RRP or LRP. Evidence acquisition A literature search was performed in August 2011 using the Medline, Embase, and Web of Science databases. Only comparative studies or clinical series including >100 cases reporting potency recovery outcomes were included in this review. Cumulative analysis was conducted using Review Manager v.4.2 software designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK). Evidence synthesis We analyzed 15 case series, 6 studies comparing different techniques in the context of RARP, 6 studies comparing RARP with RRP, and 4 studies comparing RARP with LRP. The 12- and 24-mo potency rates ranged from 54% to 90% and from 63% to 94%, respectively. Age, baseline potency status, comorbidities index, and extension of the nerve-sparing procedure represent the most relevant preoperative and intraoperative predictors of potency recovery after RARP. Available data seem to support the use of cautery-free dissection or the use of pinpointed low-energy cauterization. Cumulative analyses showed better 12-mo potency rates after RARP in comparison with RRP (odds ratio OR: 2.84; 95% confidence interval CI: 1.46–5.43; p = 0.002). Only a nonstatistically significant trend in favor of RARP was reported after comparison with LRP (OR: 1.89; p = 0.21). Conclusions The incidence of potency recovery after RARP is influenced by numerous factors. Data coming from the present systematic review support the use of a cautery-free technique. This update of previous systematic reviews of the literature showed, for the first time, a significant advantage in favor of RARP in comparison with RRP in terms of 12-mo potency rates.
Abstract Context Despite the wide diffusion of laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALP), only few studies comparing the results of these ...techniques with the retropubic radical prostatectomy (RRP) are currently available. Objective To evaluate the perioperative, functional, and oncologic results in the comparative studies evaluating RRP, LRP, and RALP. Evidence acquisition A systematic review of the literature was performed in January 2008, searching Medline, Embase, and Web of Science databases. A “free-text” protocol using the term radical prostatectomy was applied. Some 4000 records were retrieved from the Medline database; 2265 records were retrieved from the Embase database;, and 4219 records were retrieved from the Web of Science database. Three of the authors reviewed the records to identify comparative studies. A cumulative analysis was conducted using Review Manager software v.4.2 (Cochrane Collaboration, Oxford, UK). Evidence synthesis Thirty-seven comparative studies were identified in the literature search, including a single, randomised, controlled trial. With regard to the perioperative outcome, LRP and RALP were more time consuming than RRP, especially in the initial steps of the learning curve, but blood loss, transfusion rates, catheterisation time, hospitalisation duration, and complication rates all favoured LRP. With regard to the functional results, LRP and RRP showed similar continence and potency rates. Similarly, no significant differences were identified between LRP and RALP, while a single, nonrandomised, prospective study suggested advantages in terms of both continence and potency recovery after RALP, compared with RRP. With regard to the oncologic outcome, LRP and RALP were associated with positive surgical margin rates similar to those of RRP. Conclusions The quality of the available comparative studies was not excellent. LRP and RALP are followed by significantly lower blood loss and transfusion rates, but the available data were not sufficient to prove the superiority of any surgical approach in terms of functional and oncologic outcomes. Further high-quality, prospective, multicentre, comparative studies are needed.
Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, ...these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility.
We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy.
After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 0.13-0.85;
= .02) or included (0.66 0.44-0.99;
= .04).
Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.
The role of subcellular survivin compartmentalization in the biology and prognosis of prostate cancer is unclear. We therefore investigated subcellular localization of survivin in more than 3000 ...prostate cancer patients by quantitative immunohistochemistry and performed transcriptomics of 250 prostate cancer patients and healthy donors using publicly available datasets. Survivin (BIRC5) gene expression was increased in primary prostate cancers and metastases, but did not differ in recurrent vs non-recurrent prostate cancers. Survivin immunohistochemistry (IHC) staining was limited exclusively to the nucleus in 900 prostate cancers (40.0%), and accompanied by various levels of cytoplasmic positivity in 1338 tumors (59.4%). 0.5% of prostate cancers did not express survivin. Nuclear and cytoplasmic survivin staining intensities were strongly associated with each other, pT category, and higher Gleason scores. Cytoplasmic but not nuclear survivin staining correlated with high tumor cell proliferation in prostate cancers. Strong cytoplasmic survivin staining, but not nuclear staining predicted an unfavorable outcome in univariate analyses. Multivariate Cox regression analysis showed that survivin is not an independent prognostic marker. In conclusion, we provide evidence that survivin expression is increased in prostate cancers, especially in metastatic disease, resulting in higher aggressiveness and tumor progression. In addition, subcellular compartmentalization is an important aspect of survivin cancer biology, as only cytoplasmic, but not nuclear survivin accumulation is linked to biological aggressiveness and prognosis of prostate cancers.
Abstract Background Current trials are investigating radical intervention in men with metastatic prostate cancer. However, there is a lack of safety data for radical prostatectomy as therapy in this ...setting. Objective To examine perioperative outcomes and short-term complications after radical prostatectomy for locally resectable, distant metastatic prostate cancer. Design, setting, and participants A retrospective case series from 2007 to 2014 comprising 106 patients with newly diagnosed metastatic (M1) prostate cancer from the USA, Germany, Italy, and Sweden. Intervention Radical prostatectomy and extended pelvic lymphadenectomy. Outcome measurements and statistical analysis Descriptive statistics were used to present margin status, continence, and readmission, reoperation, and overall complication rates at 90 d, as well as for 21 specific complications. Kaplan-Meier plots were used to estimate survival function. Intercenter variability and M1a/ M1b subgroups were examined. Results and limitations Some 79.2% of patients did not suffer any complications; positive-margin (53.8%), lymphocele (8.5%), and wound infection (4.7%) rates were higher in our cohort than in a meta-analysis of open radical prostatectomy performed for standard indications. At a median follow-up of 22.8 mo, 94/106 (88.7%) men were still alive. The study is limited by its retrospective design, differing selection criteria, and short follow-up. Conclusions Radical prostatectomy for men with locally resectable, distant metastatic prostate cancer appears safe in expert hands for meticulously selected patients. Overall and specific complication rates related to the surgical extirpation are not more frequent than when radical prostatectomy is performed for standard indications, and the use of extended pelvic lymphadenectomy in all of this cohort compared to its selective use in localized/locally advanced prostate cancer accounts for any extra morbidity. Patient summary Men presenting with advanced prostate cancer that has spread beyond the prostate are increasingly being considered for treatments directed at the prostate itself. On the basis of results for our international series of 106 men, surgery appears reasonably safe in this setting for certain patients.
Abstract Context Despite the large diffusion of robot-assisted radical prostatectomy (RARP), literature and data on the oncologic outcome of RARP are limited. Objective Evaluate lymph node yield, ...positive surgical margins (PSMs), use of adjuvant therapy, and biochemical recurrence (BCR)–free survival following RARP and perform a cumulative analysis of all studies comparing the oncologic outcomes of RARP and retropubic radical prostatectomy (RRP) or laparoscopic radical prostatectomy (LRP). Evidence acquisition A systematic review of the literature was performed in August 2011, searching Medline, Embase, and Web of Science databases. A free-text protocol using the term radical prostatectomy was applied. The following limits were used: humans; gender (male); and publications dating from January 1, 2008. A cumulative analysis was conducted using Review Manager software v.4.2 (Cochrane Collaboration, Oxford, UK) and Stata 11.0 SE software (StataCorp, College Station, TX, USA). Evidence synthesis We retrieved 79 papers evaluating oncologic outcomes following RARP. The mean PSM rate was 15% in all comers and 9% in pathologically localized cancers, with some tumor characteristics being the most relevant predictors of PSMs. Several surgeon-related characteristics or procedure-related issues may play a major role in PSM rates. With regard to BCR, the very few papers with a follow-up duration >5 yr demonstrated 7-yr BCR-free survival estimates of approximately 80%. Finally, all the cumulative analyses comparing RARP with RRP and comparing RARP with LRP demonstrated similar overall PSM rates (RARP vs RRP: odds ratio OR: 1.21; p = 0.19; RARP vs LRP: OR: 1.12; p = 0.47), pT2 PSM rates (RARP vs RRP: OR: 1.25; p = 0.31; RARP vs LRP: OR: 0.99; p = 0.97), and BCR-free survival estimates (RARP vs RRP: hazard ratio HR: 0.9; p = 0.526; RARP vs LRP: HR: 0.5; p = 0.141), regardless of the surgical approach. Conclusions PSM rates are similar following RARP, RRP, and LRP. The few data available on BCR from high-volume centers are promising, but definitive comparisons with RRP or LRP are not currently possible. Finally, significant data on cancer-specific mortality are not currently available.
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