Health-related quality of life of patients with prostate cancer initiating GnRH agonist therapy: the PRISME study.

OBJECTIVES: To compare the evolution of health-related quality of life (HRQoL) over 6 months of GnRH agonist (GnRHa) therapy among age groups for patients with prostate cancer (PCa). PATIENTS AND METHODS: PRISME (NCT03516110) was a non-interventional, prospective study conducted in France in patients aged ≥60 years with PCa initiating GnRHa therapy within routine care. HRQoL was evaluated at baseline and after 6 months using the EORTC quality of life in ELDerly cancer patients 14 items (QLQ-ELD14) questionnaire. Cognitive status was assessed using the Mini Mental State Examination (MMSE). Analyses of covariance compared the evolution of the change from baseline of the QLQ-ELD14 scores among age groups. RESULTS: 814 patients were enrolled (245, 60-70 years; 314, 70-75 years; 252, ≥75 years). Slight or no changes were observed in each QLQ-ELD14 dimension between baseline and 6 months, overall and by age. In the primary effectiveness analysis, there was no difference among age groups in the change from baseline in QLQ-ELD14 scores. Baseline cognitive status was lower in the oldest age group, but there were no changes in all age groups. As expected, sexual function declined in all age groups. CONCLUSION: GnRHa therapy influence on HRQoL, cognition and sexuality appeared independent of age.

Prostate cancer that has spread to other parts of the body is called "advanced prostate cancer." Hormone therapy is a common treatment for high risk localized and advanced prostate cancer. It works by lowering hormone levels, causing prostate cancers to grow more slowly or shrink. But, side effects from this kind of treatment can affect a patient's quality of life. Common side effects of hormone therapy include a loss of sex drive, erectile dysfunction, bone weakening, hot flushes, or mood disorders. Most patients with prostate cancer are over the age of 60 years, but elderly patients are often excluded from clinical trials, meaning that we lack data about them. This study assessed if there was a link between age and health-related quality of life in men with advanced prostate cancer treated with hormone therapy. The study included 814 men with advanced prostate cancer who were over 60 years old and had started a type of hormone therapy called gonadotropin-releasing hormone agonist (GnRHa) therapy. The results showed that health-related quality of life was similar after 6 months of hormone therapy, in the overall group of patients and in the different age groups (60­70, 70­75, and over 75 years of age). Cognitive impairment occurred about twice as often in patients aged over 75 years than among younger patients, before initiation of hormone therapy. Cognitive impairment was likely caused by ageing and was not associated with hormone therapy treatment. Sexual function decreased in all age groups, particularly in patients aged 60­70 years. This study did not reveal any major impact of hormone therapy on health-related quality of life in older men with advanced prostate cancer, after a 6-month period and the use of routine questionnaires.

Chromogranin A: a useful biomarker in castration-resistant prostate cancer.

PURPOSE: The natural history of prostate cancer (PC) almost always evolves to castration-resistant prostate cancer (CRPC) status, sometimes comprising pure or mixed neuroendocrine prostate cancers (NEPC) differentiation. In CRPC, monitoring using only prostate-specific antigen (PSA) is not optimal since neuroendocrine differentiated cells do not secrete PSA. Thus, monitoring with PSA and chromogranin A (CgA) may be useful. This review aims to evaluate evidence for the usefulness of CgA assessments during the monitoring of prostate cancer. METHOD: This review was based on three recent meta-analysis concerning CgA and prostate cancer. Further data were obtained from PubMed and Embase databases by searches using keywords, including chromogranin A and prostate cancer. RESULTS: CgA levels remain largely unchanged during the early PC evolution. The development of NEPC is characterised by lower PSA secretion and increased CgA secretion. Data supporting the prognostic value of high CgA baseline levels for survival are contrasting and scarce. However, increasing CgA levels early during treatment of metastatic (m)CRPC suggests resistance to treatment and predicts shorter survival, particularly in men with high baseline levels of CgA levels. In men with mCRPC, the first-line chemotherapy may be more appropriate than other agents when baseline CgA levels are high. Also, increasing CgA levels during treatment may indicate disease progression and may warrant a change of therapy. CONCLUSION: CgA monitoring at baseline and regularly during mCRPC management may be useful for monitoring disease evolution. An increased CgA baseline levels and increasing CgA levels may assist physicians with choosing and modifying therapy.

Long-term functional and oncological outcomes of nerve-sparing and prostate capsule-sparing cystectomy: a single-centre experience.

OBJECTIVES: To evaluate the technical feasibility, oncological and functional outcomes of nerve sparing cystoprostatectomy (NSCP) and prostate capsule-sparing cystectomy (PCSC) for the treatment of organ-confined bladder cancer at a single referral centre. PATIENTS AND METHODS: From April 2001 to June 2012, 60 patients underwent PCSC and 47 were treated with NSCP. Inclusion criteria for PCSC were: fully informed consent for the well-motivated patient; negative transurethral resection of the bladder neck; normal prostatic specific antigen (PSA) level (defined as <4 ng/dL during the first year of the study, which was later lowered to 2.5 ng/dL); and normal transrectal ultrasonography, with biopsy for any suspicious nodule. Patients received a complete oncological and functional follow-up. The Kaplan-Meier method was used to depict survival outcomes after surgery. RESULTS: After a median follow-up of 73 and 62 months for PCSC and NSCP, respectively, the 5-year cancer-specific survival was 90% for the PCSC group and 78% for the NSCP group (P = 0.055). Considering complications within 30 days after surgery, 13% and 21% patients had Clavien ≥III complications in the PCSC and NSCP groups, respectively (P = 0.2). For functional outcomes, at 3 months after surgery, 54 (90%) and 24 (51%) patients reported full recovery of daytime urinary continence in the PCSC and NSCP groups, respectively (P < 0.001); and for erectile function recovery, 32 (53%) and four (9%) patients in the PCSC group and in the NSCP group were respectively potent without any treatment (P < 0.001). CONCLUSIONS: NSCP and PCSC are appropriate for a subset of patients with bladder cancer, with excellent oncological and functional results. These surgical procedures should be proposed to well-motivated patients.

Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: To evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). MATERIALS AND METHODS: Among 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic patients with mCRPC, who experienced biochemical progression on treatment with AA+P 10 mg/day, were included. A corticosteroid switch to AA+D 0.5 mg/day at PSA increase was administered until radiological and/or clinical progression. The primary endpoint was progression-free-survival (PFS). A prognostic score based on independent prognostic factors was defined. RESULTS: The median time to PSA progression on AA+P was 8.94 months. The median PFS on AA+D and AA+corticosteroids (P then D) was 10.35 and 20.07 months, respectively. A total of 56.25% of patients showed a decrease or stabilization in PSA levels after the switch. In univariate analysis, three markers of switch efficiency were significantly associated with a longer PFS: long hormone-sensitivity duration (≥5 years; median PFS 16.62 vs 4.17 months, hazard ratio [HR] 0.30, 90% confidence interval [CI] 0.16-0.56); low PSA level at the time of switch (<50 ng/mL; median PFS 15.21 vs 3.86 months, HR 0.33, 90% CI 0.18-0.60); and short time to PSA progression on AA+P (<6 months; median PFS 28.02 vs 6.65 months, HR 0.41 (90% CI 0.21-0.81). In multivariate analysis, hormone sensitivity duration and PSA level were independent prognostic factors. CONCLUSION: A steroid switch from P to D appears to be a safe and non-expensive way of obtaining long-term responses to AA in selected patients with mCRPC. A longer PFS has been observed in patients with previous long hormone sensitivity duration, and/or low PSA level and/or short time to PSA progression on AA+P.

Biochemical recurrence-free conditional probability after radical prostatectomy: A dynamic prognosis.

OBJECTIVE: To estimate the conditional biochemical recurrence-free probability and to develop a predictive model according to the disease-free interval for men with clinically localized prostate cancer treated with minimally invasive radical prostatectomy. METHODS: The study population consisted of 3576 consecutive patients who underwent laparoscopic radical prostatectomy and 2619 men treated with robotic radical prostatectomy in the past 15 years at Institute Mutualiste Montsouris, Paris, France. Biochemical recurrence was defined as serum prostate-specific antigen ≥0.2 ng/dL. Univariable and multivariable survival analyses were carried out to identify the prognostic factors for overall free-of-biochemical recurrence probability and conditional survival with respect to the years from surgery without recurrence. A detailed nomogram for the static and dynamic prognosis of biochemical recurrence was developed and internally validated. RESULTS: The median follow-up period was 8.49 years (interquartile range 4.01-12.97), and 1148 (19%) patients experienced biochemical recurrence. Significant variables associated with biochemical recurrence in the multivariable model included preoperative prostate-specific antigen, positive surgical margins, extracapsular extension, pathological Gleason ≥4 + 3 and laparoscopic surgery (all P < 0.001). Conditional survival probability decreased with increasing time without biochemical recurrence from surgery. When stratified by prognosis factors, the 5- and 10-year conditional survival improved in all cases, especially in men with worse prognosis factors. The concordance index of the nomogram was 0.705. CONCLUSIONS: Conditional survival provides relevant information on how prognosis evolves over time. The risk of recurrence decreases with increasing number of years without disease. An easy-to-use nomogram for conditional survival estimates can be useful for patient counseling and also to optimize postoperative follow-up strategies.

Comparative Analysis of Partial Gland Ablation and Radical Prostatectomy to Treat Low and Intermediate Risk Prostate Cancer: Oncologic and Functional Outcomes.

PURPOSE: We analyzed the oncologic and functional outcomes of partial gland ablation compared with robot-assisted radical prostatectomy in patients with low and intermediate risk prostate cancer. MATERIALS AND METHODS: A total of 1,883 patients underwent robot-assisted radical prostatectomy and 373 underwent partial gland ablation from July 2009 to September 2015. We selected 1,458 of these participants for analysis, including 1,222 and 236 treated with robot-assisted radical prostatectomy and partial gland ablation, respectively. Patients had a Gleason score of 3 + 3 or 3 + 4, clinical stage T2b or less, prostate specific antigen 15 ng/dl or less, unilateral disease and life expectancy greater than 10 years. Propensity score matching analysis (1:2) was applied in the overall robot-assisted radical prostatectomy sample, which selected 472 patients for comparison. For partial gland ablation 188 men underwent high intensity focused ultrasound and 48 underwent cryotherapy. Oncologic outcomes were analyzed in terms of the need for salvage treatment. Partial gland ablation failure was defined as any positive control biopsy after treatment. Functional outcomes were assessed by validated questionnaires. RESULTS: Matching was successful across the 2 groups, although men treated with partial gland ablation were older (p <0.001). Mean followup in the partial gland ablation group was 38.44 months. Partial gland ablation failure was observed in 68 men (28.8%), including 53 (28.1%) treated with high intensity focused ultrasound and 15 (31.2%) treated with cryotherapy. Partial gland ablation was associated with a higher risk of salvage treatment (HR 6.06, p <0.001). Complications were comparable between the groups (p = 0.06). Robot-assisted radical prostatectomy was associated with less continence recovery and a lower potency rate 3, 6 and 12 months after surgery (p <0.001). CONCLUSIONS: In select patients with organ confined prostate cancer partial gland ablation offered good oncologic control with fewer adverse effects that required additional treatments. Potency and continence appeared to be better preserved after partial gland ablation.

Modified York Mason technique for repair of iatrogenic recto-urinary fistula: 20 years of the Montsouris experience.

PURPOSE: Iatrogenic recto-urinary fistulas are a disastrous complication of therapeutic interventions on the prostate. Many surgical approaches have been described to repair recto-urinary fistulas and no consensus has been reached regarding the better approach. The objective of this study is to present the results of our updated 20-year experience in the surgical management of recto-urinary fistula using a modified York Mason procedure. METHODS: We proceed to a retrospective single-institution review of surgically treated patients for iatrogenic recto-urinary fistulas between 1998 and 2017 by the modified York Mason technique. Descriptive analysis of our population was performed. Continuous and categorical variables were compared using Mann-Whitney and Fischer tests, respectively. All tests were two-sided with a significance level set at p value < 0.05. RESULTS: We included 30 consecutive patients treated for iatrogenic recto-urinary fistula. The median follow-up was 76 months (2-195). The median size of the fistula was 5 mm (2-20). Successful healing of the recto-urinary fistula was observed in 80, 97, and 100% of patients after 1, 2, or 3 York Mason procedure. During the study period, no one single case of acquired urinary incontinence or durable fecal incontinence has been observed. CONCLUSIONS: Our modified York Mason technique is a reliable and effective procedure with a 100% success rate for the repair of small iatrogenic recto-urinary fistulas in non-irradiated patients. It has a very low morbidity rate, and no case of postoperative urine or fecal incontinence has been observed.

Comparison of cell cycle progression score with two immunohistochemical markers (PTEN and Ki-67) for predicting outcome in prostate cancer after radical prostatectomy.

PURPOSE: Previous studies of the cell cycle progression (CCP) score in surgical specimens of prostate cancer (PCa) in patients treated by radical prostatectomy (RP) demonstrated significant association with time to biochemical recurrence (BCR). In this study, we compared the ability of the CCP score and the expression of PTEN or Ki-67 to predict BCR in a cohort of patients treated by RP. Finally, we constructed the best predictive model for BCR, incorporating biomarkers and relevant clinical variables. MATERIALS AND METHODS: The study population consisted of 652 PCa patients enrolled in a retrospective cohort and who had RP surgery in French urological centers from 2000 to 2007. RESULTS: Among the 652 patients with CCP scores and complete clinical data, BCR events occurred in 41%, and the median time from surgery to the last follow-up among BCR-free patients was 72 months. In univariate Cox analysis, the continuous CCP score and positive Ki-67 predicted recurrence with a HR of 1.44 (95% CI 1.17-1.75; p = 5.3 × 10-4) and 1.89 (95% CI 1.38-2.57; p = 1.6 × 10-4), respectively. In contrast, PTEN expression was not associated with BCR risk. Of the three biomarkers, only the CCP score remained significantly associated in a multivariable Cox model (p = 0.026). The best model incorporated CAPRA-S and CCP scores as predictors, with HRs of 1.32 and 1.24, respectively. CONCLUSION: The CCP score was superior to the two IHC markers (PTEN and Ki-67) for predicting outcome in PCa after RP.

Biochemical recurrence after radical prostatectomy: what does it mean?

BACKGROUND: Radical prostatectomy (RP) has been used as the main primary treatment for prostate cancer (PCa) for many years with excellent oncologic results. However, approximately 20-40% of those patients has failed to RP and presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been the pivotal tool for recurrence diagnosis, but there is no consensus about the best PSA threshold to define BCR until this moment. The natural history of BCR after surgical procedure is highly variable, but it is important to distinguish biochemical and clinical recurrence and to find the correct timing to start multimodal treatment strategy. Also, it is important to understand the role of each clinical and pathological feature of prostate cancer in BCR, progression to metastatic disease and cancer specific mortality (CSM). Review design: A simple review was made in Medline for articles written in English language about biochemical recurrence after radical prostatectomy. OBJECTIVE: To provide an updated assessment of BCR definition, its meaning, PCa natural history after BCR and the weight of each clinical/pathological feature and risk group classifications in BCR, metastatic disease and CSM.

External validation of a nomogram for identification of pathologically favorable disease in intermediate risk prostate cancer patients.

OBJECTIVE: To establish an external validation of the new nomogram from Gandaglia et al which provides estimates of the probability of pathological favorable disease in pre-operatively defined intermediate-risk PCa. PATIENTS AND METHODS: Overall, 2928 intermediate-risk PCa patients according to the D'Amico classification undergoing RP and bilateral lymph node dissection in seven academic centres between 2000 and 2011. Pathologically favorable PCa was defined as low-grade organ-confined disease. The Receiver Operating Characteristic (ROC) curve was obtained to quantify the overall accuracy (Area Under the Curve, AUC) of the model to predict specimen-confined (SC) disease. Calibration curve was then constructed to illustrate the relationship between the risk-estimates obtained by the model and the observed proportion of SC disease. Kaplan-Meier method was used for PSA recurrence-free survival (PSA-RFS) assessment. RESULTS: Median age was 68 years. 10.6% patients finally presented pathologically favorable disease characteristics at RP. A higher PSAD (OR = 0.01; 95%CI = 0.00-0.04; P < 0.0001) and percentage of positive cores (OR = 0.97; 95%CI = 0.96-0.98; P < 0.0001) were associated with a reduced probability of favorable disease at RP in multivariate analysis. ROC curve analysis showed strongest accuracy of the model (AUC = 0.82; 95%CI = 0.79-0.84). Favorable PCa had a significantly better PSA recurrence-free survival rates as compared to unfavorable PCa after RP (94.2% vs 74.4% at 4 years, P < 0.0001). CONCLUSIONS: This external validation of the Gandaglia nomogram shows relevant accuracy with one out of ten patients in this intermediate risk PCa group with pathologically proven organ-confined disease. This validated risk calculator can help physician to distinguish favorable intermediate risk PCa that can be treated by conservative approach or safer nerve-sparing surgery.

Effect of Prior Focal Therapy on Perioperative, Oncologic and Functional Outcomes of Salvage Robotic Assisted Radical Prostatectomy.

PURPOSE: We assessed the impact of focal therapy on perioperative, oncologic and functional outcomes in men who underwent salvage robotic assisted radical prostatectomy compared to primary robotic assisted radical prostatectomy. MATERIALS AND METHODS: Focal therapy was performed in patients presenting with Gleason score 3 + 3 or 3 + 4, clinical stage cT2a or less, serum prostate specific antigen 15 ng/ml or less, unilateral positive biopsy, maximum length of any positive core less than 10 mm and life expectancy greater than 10 years. Focal therapy was defined as target ablation of the index lesion plus a 1 cm safety margin in the normal ipsilateral prostatic parenchyma. The salvage group included 22 men who underwent salvage prostatectomy after focal therapy failure. The primary group was defined using matched pair 1:2 selection of 44 of 2,750 patients treated with primary prostatectomy. The primary and secondary end points were the between group differences in functional and oncologic outcomes, respectively. RESULTS: Complication rates were comparable (p >0.05). Pad-free probability was comparable between the groups at 1 and 2 years (p = 0.8). Recovery of erectile function was significantly lower after salvage robotic assisted radical prostatectomy (p = 0.008), which also showed a significantly lower probability of cumulative biochemical recurrence-free survival compared to primary robotic assisted radical prostatectomy (56.3% vs 92.4% at 2 years, p = 0.001). Salvage prostatectomy demonstrated a significantly increased risk of biochemical recurrence (HR 4.8, 95% CI 1.67-13.76, p = 0.004). Study limitations included the retrospective nature, the lack of randomization and the short followup. CONCLUSIONS: Salvage robotic assisted radical prostatectomy after focal therapy failure is feasible with acceptable complication rates. However, patients assigned to primary focal therapy should be advised about a poorer prognosis in terms of oncologic control and lower erectile recovery rates in case of a future salvage surgery.

Surgical method influences specimen margins and biochemical recurrence during radical prostatectomy for high-risk prostate cancer: a systematic review and meta-analysis.

PURPOSE: To perform a meta-analysis comparing the rates of positive surgical margins (PSM) and biochemical recurrence (BCR) between open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP) in patients with high-risk prostate cancer. METHODS: A systematic review was performed on Pubmed, Embase and Scopus databases in August 2016, according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. References retrieved were evaluated using the Newcastle-Ottawa scale and the Black and Down's tool for quality assessment. RESULTS: Nine retrospective cohorts comparing ORP and RARP were selected and included in the meta-analysis. All studies reported the PSMs. Patients treated with RARP presented less risk of PSMs (risk difference -0.04, p 0.02) than those treated with ORP. Five articles reported hazard ratios for BCR-free survival. Patients treated with RARP had less risk of BCR (HR 0.72, 95% CI 0.58-0.89) than those treated with ORP. Reports for PSM assessment were considered of adequate quality, while the studies retrieved for BCR assessment were considered limited because of the heterogeneity of their results. CONCLUSION: Patients with high-risk prostate cancer treated with RARP have less risk of having PSM and BCR when compared to those treated with ORP. A strong conclusion is precluded due to the observational nature of the studies retrieved for our analysis.

Improved decision making in intermediate-risk prostate cancer: a multicenter study on pathologic and oncologic outcomes after radical prostatectomy.

BACKGROUND: Prognoses for intermediate-risk prostate cancer (PCa) remain heterogeneous. Improved substratification could optimize treatment and monitoring strategies. The objective was to validate this subclassification in a radical prostatectomy (RP) series. METHODS: Between 2000 and 2011, 4038 patients who underwent RP for intermediate-risk PCa in seven French academic centers were included. Unfavorable intermediate-risk (UIR) PCa was defined as having a primary Gleason score of 4, ≥50% positive biopsy cores (PPBC), or more than one D'Amico intermediate-risk factor (i.e., cT2b, PSA 10-20, or Gleason score 7). Remaining PCa cases were classified as favorable. Main endpoints were pathologic results (pT stage, final Gleason score, surgical margin status), and oncologic outcomes were assessed according to PSA recurrence-free survival (PSA-RFS). Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. RESULTS: Median follow-up was 48 months (95% CI = [45-49]). Patients with UIR had worse PSA-RFS (68.17 vs. 81.98% at 4 years, HR = 1.97, 95% CI = [1.71; 2.27], p < 0.0001) compared to those with a favorable disease. The need for adjuvant therapy was significantly greater for UIR patients (43.5 vs. 29.2%, p < 0.0001). In multivariate analysis, primary Gleason score of 4 (HR = 1.81, 95% CI = [1.55; 2.12], p < 0.0001) and PPBC ≥ 50% (HR = 1.26, 95% CI = [1.02; 1.56], p = 0.0286) were significant preoperative predictors for worse PSA-RFS. CONCLUSIONS: This study highlights the heterogeneity of NCCN intermediate-risk patients and validates (in a large RP cohort) the previously proposed subclassification for this group. This classification can significantly predict both pathologic and oncologic outcomes. This easy-to-use stratification could help physicians' decision making. Prospective study and new tools as genomic tests and novel molecular-based approaches can improve this stratification in the future for patient counseling.

Focal cryotherapy: step by step technique description.

INTRODUCTION AND OBJECTIVE: Focal cryotherapy emerged as an efficient option to treat favorable and localized prostate cancer (PCa). The purpose of this video is to describe the procedure step by step. MATERIALS AND METHODS: We present the case of a 68 year-old man with localized PCa in the anterior aspect of the prostate. RESULTS: The procedure is performed under general anesthesia, with the patient in lithotomy position. Briefly, the equipament utilized includes the cryotherapy console coupled with an ultrasound system, argon and helium gas bottles, cryoprobes, temperature probes and an urethral warming catheter. The procedure starts with a real-time trans-rectal prostate ultrasound, which is used to outline the prostate, the urethra and the rectal wall. The cryoprobes are pretested and placed in to the prostate through the perineum, following a grid template, along with the temperature sensors under ultrasound guidance. A cystoscopy confirms the right positioning of the needles and the urethral warming catheter is installed. Thereafter, the freeze sequence with argon gas is started, achieving extremely low temperatures (-40ºC) to induce tumor cell lysis. Sequentially, the thawing cycle is performed using helium gas. This process is repeated one time. Results among several series showed a biochemical disease-free survival between 71-93% at 9-70 month- follow-up, incontinence rates between 0-3.6% and erectile dysfunction between 0-42% (1-5). CONCLUSIONS: Focal cryotherapy is a feasible procedure to treat anterior PCa that may offer minimal morbidity, allowing good cancer control and better functional outcomes when compared to whole-gland treatment.

First off-time treatment prostate-specific antigen kinetics predicts survival in intermittent androgen deprivation for prostate cancer.

BACKGROUND: Prostate-specific antigen (PSA) doubling time is relying on an exponential kinetic pattern. This pattern has never been validated in the setting of intermittent androgen deprivation (IAD). Objective is to analyze the prognostic significance for PCa of recurrent patterns in PSA kinetics in patients undergoing IAD. METHODS: A retrospective study was conducted on 377 patients treated with IAD. On-treatment period (ONTP) consisted of gonadotropin-releasing hormone agonist injections combined with oral androgen receptor antagonist. Off-treatment period (OFTP) began when PSA was lower than 4 ng/ml. ONTP resumed when PSA was higher than 20 ng/ml. PSA values of each OFTP were fitted with three basic patterns: exponential (PSA(t) = λ.e(αt)), linear (PSA(t) = a.t), and power law (PSA(t) = a.t(c)). Univariate and multivariate Cox regression model analyzed predictive factors for oncologic outcomes. RESULTS: Only 45% of the analyzed OFTPs were exponential. Linear and power law PSA kinetics represented 7.5% and 7.7%, respectively. Remaining fraction of analyzed OFTPs (40%) exhibited complex kinetics. Exponential PSA kinetics during the first OFTP was significantly associated with worse oncologic outcome. The estimated 10-year cancer-specific survival (CSS) was 46% for exponential versus 80% for nonexponential PSA kinetics patterns. The corresponding 10-year probability of castration-resistant prostate cancer (CRPC) was 69% and 31% for the two patterns, respectively. Limitations include retrospective design and mixed indications for IAD. CONCLUSION: PSA kinetic fitted with exponential pattern in approximately half of the OFTPs. First OFTP exponential PSA kinetic was associated with a shorter time to CRPC and worse CSS.

Non-metastatic castrate-resistant prostate cancer: a call for improved guidance on clinical management.

BACKGROUND: Guidelines on the clinical management of non-metastatic castrate-resistant prostate cancer (nmCRPC) generally focus on the need to continue androgen deprivation therapy and enrol patients into clinical trials of investigational agents. This guidance reflects the lack of clinical trial data with established agents in the nmCRPC patient population and the need for trials of new agents. AIM: To review the evidence base and consider ways of improving the management of nmCRPC. CONCLUSION: Upon the development of castrate resistance, it is essential to rule out the presence of metastases or micrometastases by optimising the use of bone scans and possibly newer procedures and techniques. When nmCRPC is established, management decisions should be individualised according to risk, but risk stratification in this diverse population is poorly defined. Currently, prostate-specific antigen (PSA) levels and PSA doubling time remain the best method of assessing the risk of progression and response to treatment in nmCRPC. However, optimising imaging protocols can also help assess the changing metastatic burden in patients with CRPC. Clinical trials of novel agents in nmCRPC are limited and have problems with enrolment, and therefore, improved risk stratification and imaging may be crucial to the improved management. The statements presented in this paper, reflecting the views of the authors, provide a discussion of the most recent evidence in nmCRPC and provide some advice on how to ensure these patients receive the best management available. However, there is an urgent need for more data on the management of nmCRPC.

Relationship between non-suspicious MRI and insignificant prostate cancer: results from a monocentric study.

OBJECTIVES: To assess whether non-suspicious multiparametric magnetic-resonance imaging (mpMRI) was associated with no cancer or indolent prostate cancer (PCa) in subsequent biopsies. PATIENTS AND METHODS: Retrospective analyses of a prospective database were conducted between 2009 and 2013. It included men with an abnormal digital rectal examination and/or prostate-specific antigen levels <20 ng/mL and a non-suspicious multiparametric MRI (Likert score <3). Participants underwent a systematic 12-extended-core biopsy ultrasound protocol (STD). Indolent PCa was defined as a single core with a Gleason score of 6 (3 + 3) and a cancer-core length of ≤4 mm. RESULTS: Seventy-eight patients with a negative MRI were included in the study; median patient age was 62 years (IQR 50-74). Median PSA level was 7.15 ng/mL, with a median PSA density of 0.15. The digital rectal examination was abnormal in eight cases. From MRI, 53 patients were Likert 2, 25 patients were Likert 1, and median prostate volume was 56.5 mL. From biopsies, no cancer was found in 92.3 % (n = 72). PCa was histologically confirmed in six patients (7.7 %): five cases were indolent (as defined above); only one patient had a cancer core of 5 mm long, with a Gleason score of 6 (3 + 3). All six patients were within the low-risk group according to the D'Amico classification. CONCLUSION: Men with non-suspicious mpMRI are likely to have no or indolent PCa in subsequent biopsies.

A nomogram predicting the cancer-specific mortality in patients eligible for radical cystectomy evaluating clinical data and neoadjuvant cisplatinum-based chemotherapy.

PURPOSE: Despite the increasing number of studies confirming the importance of neoadjuvant chemotherapy (NC) in patients before radical cystectomy (RC) for bladder cancer (BCa), NC remains underused. The aim of our study was to develop a nomogram predicting the cancer-specific mortality (CSM) of patients who underwent RC for transitional BCa, evaluating the available clinical information and the NC. MATERIALS AND METHODS: We identified 423 patients who underwent RC and pelvic lymph node dissection, treated or not with NC, in two European high-volume centers between 2007 and 2013. Chi-square and Student's t tests were used to evaluate differences between groups. Kaplan-Meier curves were used to assess time to cancer-specific (CSS) and overall survival (OS). Uni- (UVA) and multivariable (MVA) Cox regression analyses were developed to address predictors of CSS and OS. A nomogram based on the Cox regression coefficient was developed to show the impact of NC on CSM. RESULTS: Mean follow-up was 20.3 months. Our population had mainly pT2 disease (77.1%), and 19.4% had preoperative cisplatinum-based NC. NC showed better CSS at UVA (p = 0.014) and MVA (odds ratio: 0.44; p = 0.043). Overall, the 3-year OS and the CSS rate were 69.3 and 79%, respectively. The nomogram developed to predict the 36-month CSM showed predictive accuracy of 67%. CONCLUSIONS: We developed the first nomogram predicting the 36-month CSM rate in patients with high-risk BCa according to the clinical data. Moreover, we demonstrate that preoperative cisplatinum-based chemotherapy is associated with better CSS.

Androgen deprivation therapy in castrate-resistant prostate cancer: how important is GnRH agonist backbone therapy?

BACKGROUND: A growing number of treatment options exist to treat metastatic castrate-resistant prostate cancer (mCRPC), and with these newer options, many questions about optimising treatment remain unanswered. One recommendation that may potentially be overlooked by practitioners is that androgen deprivation therapy (ADT) should be maintained when CRPC develops and when treatment with any of the newer agents is initiated. AIM: However, to emphasise this recommendation, it is valuable to interrogate the evidence for maintaining ADT in different clinical situations. OUTCOME: This statement, reflecting the views of the authors, provides a discussion of this evidence and the rationale behind the recommendation that ADT should be continued in CRPC.