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Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9×10-7 and GAB2, p = 2.0×10-6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS-versus treatment for the initial management of patients with low-risk PC.

Background: A wide range of disorders can be detected in the urine. Tumor-modifying proteins in the urine may serve as a diagnostic tool for cancer patients and the alterations in their profiles may indicate efficacies of chemotherapy, radiotherapy, and surgery. Methods: We focused on urinary proteomes of patients with prostate cancer and identified tumor-modifying proteins in the samples before and after prostatectomy. Protein array analysis was conducted to evaluate a differential profile of tumor-promoting cytokines, while mass spectrometry-based global proteomics was conducted to identify tumor-suppressing proteins. Results: The result revealed striking differences by prostatectomy. Notably, the urine from the post-prostatectomy significantly decreased the tumorigenic behaviors of prostate tumor cells as well as breast cancer cells. We observed that angiogenin, a stimulator of blood vessel formation, was reduced in the post-prostatectomy urine. By contrast, the levels of three cell-membrane proteins such as prostasin (PRSS8), nectin 2 (PVRL2), and nidogen 1 (NID1) were elevated and they acted as extracellular tumor-suppressing proteins. These three proteins, given extracellularly, downregulated tumorigenic genes such as Runx2, Snail, and transforming growth factor beta and induced apoptosis of tumor cells. However, the role of NID1 differed depending on the location, and intracellular NID1 was tumorigenic and reduced the percent survival. Conclusions: This study demonstrated that prostatectomy remarkably altered the profile of urinary proteomes, and the post-prostatectomy urine provided tumor-suppressive proteomes. The result sheds novel light on the dynamic nature of the urinary proteomes and a unique strategy for predicting tumor suppressors. [ABSTRACT FROM AUTHOR]

With the advancement of early detection tools for prostate cancer and ability to better localize disease, there has been increased interest in focal or targeted therapies that carry less morbidity than traditional whole-gland treatments. The Sonablate® high-intensity focused ultrasound (HIFU) device has Food and Drug Administration (FDA) 510(K) clearance in the United States for ablation of prostate tissue. HIFU utilizes an ultrasound (US) transducer that focuses US beams on a preset point as much as 4 cm from the energy source without injuring intervening tissue. The Sonablate system guides the surgeon step-by-step to perform effective ablation of a target lesion. The surgeon can assess treatment effect with tissue change monitoring, and care is taken to prevent rectal wall injury. We believe hemiablation is the most favorable focal HIFU treatment to optimize cancer control and minimize the side effects associated with whole gland therapy. We recommend considering HIFU ablation as an extension of active surveillance rather than definitive treatment. Further research on long-term oncologic and functional outcomes is warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Determining the optimal treatment for biochemical recurrence (BCR) after radical prostatectomy (RP) is challenging. OBJECTIVE:We evaluated the ability of CCP score (a prognostic RNA expression signature) to discriminate between systemic disease and local recurrence in patients with BCR after RP. METHODS: Sixty patients with BCR after RP were selected for analysis based on: 1) metastatic disease, 2) non-response to salvage external beam radiotherapy (EBRT), and 3) durable response to salvage EBRT. CCP scores were generated from the RNA expression of 46 genes. Logistic regression assessed the association between CCP score and patient group. RESULTS: Passing CCP scores were generated for 47 patients with complete clinical and pathologic data. CCP score predicted clinical status when comparing patients with metastatic disease or non-responders to salvage therapy to patients with durable response (p = 0.006). CCP score remained significantly predictive of clinical status after accounting for time to BCR, PSA level at BCR, and Gleason score (p = 0.0031). CONCLUSIONS: Elevated CCP score was associated with increased risk of systemic disease, indicating that CCP score may be useful in identifying patients with BCR who are most likely to benefit from salvage radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose Urinary continence is a driver of quality of life after radical prostatectomy. In this study we evaluated the impact of a biological bladder neck sling on the return of urinary continence after robot-assisted radical prostatectomy. Materials and Methods This study compared early continence in patients undergoing robot-assisted radical prostatectomy with a sling and without a sling in a 2-group, 1:1, parallel, randomized controlled trial. Patients were blinded to group assignment. The primary outcome was defined as urinary continence (0 to 1 pad per day) at 1 month postoperatively. Inclusion criteria were organ confined prostate cancer and a prostate specific antigen less than 15 ng/ml. Exclusion criteria were any prior surgery on the prostate, a history of neurogenic bladder and history of pelvic radiation. A chi-squared test was used for the primary outcome. Results A total of 147 patients were randomized (control 74, sling 73) and 92% were available for primary end point analysis at 1 month. There were no significant differences in baseline or perioperative data except that operating room time was 20.1 minutes longer for the sling group (p=0.04). The continence rate was similar between the control and sling groups at 1 month (47.1% vs 55.2%, p=0.34) and 12 months (86.7% vs 94.5%, p=0.15), respectively. Adverse events were similar between the control and sling groups (10.8% vs 13.7%, p=0.59). Conclusions The application of an absorbable urethral sling at robot-assisted radical prostatectomy was well tolerated with no increase in obstructive symptoms in this randomized trial. However, the sling failed to show a significant improvement in continence. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between operative time, approach, and length of stay (LOS) in partial nephrectomy (PN), radical prostatectomy (RP), and adrenalectomy (AD). Materials and Methods: Using the National Surgical Quality Improvement Program database, we identified all PN, RP, and AD from 2010 to 2012. Non-prostate cancer RP were excluded. The primary outcome was LOS. Descriptive comparisons were drawn between open and minimally invasive surgery (MIS) for each surgery. Multiple linear regression assessed the impact of open versus MIS and operative time on LOS when controlling for confounders. Results: We identified 3760 PN (60% MIS), 12,081 RP (82% MIS), and 1684 AD (76% MIS) cases for inclusion. Differences in operative time were identified. In PN and RP, MIS mean operative time was 10 to 23 minutes longer ( p<0.001 each); while for AD, open was 35 minutes longer ( p<0.001). Open procedures had consistently longer median LOS ( p<0.001 all). Results of the linear regression are given next. Conclusions: Operative time and surgical approach are directly associated with LOS, independent of complications and patient comorbidities. [ABSTRACT FROM AUTHOR]

Pelvic lymphadenectomy for prostate cancer is an important tool in the prognostication of the disease in selected patients who are at risk of occult lymph node metastases. This procedure, usually performed in conjunction with radical prostatectomy, had progressed successfully from an open approach to the current robot-assisted approach. The following article and accompanying video describe the surgical technique of robot-assisted pelvic lymphadenectomy for prostate cancer. We also discuss the indications, patient selection, preparation, complications, and tips to avoid the major pitfalls in the procedure. [ABSTRACT FROM AUTHOR]

Information about the topics discussed at the third annual Interactive Genitourinary Cancer Conference (IGUCC3) that was held in Budapest, Hungary from April 30 to May 1, 2011 is presented. Topics include the promotion of multidisciplinary collaboration, the available treatment options for prostate cancer, and the challenges in the management of metastatic castration-resistant prostate cancer. It also explores the use of imaging methods, biomarkers and biopsy-based techniques in cancer patients.

Purpose: We characterized prostate cancer focality in regard to clinicopathological features, prognostic value and impact on biochemical outcome. Materials and Methods: We retrospectively reviewed the records of 1,366 patients in our prospective database who underwent radical prostatectomy between 1999 and 2010 for clinically localized prostate cancer with pathological evaluation using whole mount sectioning techniques and tumor mapping. Unifocal disease was defined as the identification of a solitary cancer focus in the prostate without additional tumor foci or satellite lesions, ie multifocal disease, on histopathological evaluation. Cox regression modeling was used to identify predictors of biochemical progression among groups. Results: A total of 184 patients (13%) fulfilled our unifocal tumor criteria. Unifocal tumors tended to be smaller in volume and in greatest diameter than multifocal tumors (p <0.0001 and <0.005, respectively). Of patients with pathologically insignificant disease the relative proportion with unifocal tumors increased to 28% from 13% in the overall cohort (p <0.0005). Also, tumor focality failed to predict biochemical recurrence in univariate and multivariate models. Accordingly we noted no significant differences in 5-year biochemical recurrence-free survival for unifocal and multifocal tumors (66% and 61%, respectively, p = 0.76). Limitations of this study include its retrospective nature. Conclusions: In this study tumor focality failed to predict patients likely to experience biochemical failure. Tumor characteristics were similar regardless of focality. However, unifocal tumors had smaller volume and were more commonly seen as clinically insignificant compared to multifocal tumors. [ABSTRACT FROM AUTHOR]

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To report the long-term outcome of high-grade prostate cancer treated with radical prostatectomy (RP) as initial monotherapy, analyse the effect of clinical and pathological variables on survival, and report cancer-related symptoms. PATIENTS AND METHODS A retrospective chart review was conducted to identify patients with Gleason 8–10 prostate cancer found on pathological review in men undergoing RP as initial therapy for clinically localized disease between 1988 and 2005. Kaplan-Meier analysis was used to calculate event-free survival. Univariable and multivariable analyses were used to assess the effects of clinical and pathological variables on prostate-specific antigen (PSA) recurrence. RESULTS After excluding 20 patients, 119 were identified with pathologically confirmed high-grade cancers at the time of RP. The overall median (interquartile range) follow-up was 73 (41–113) months. Twenty-four (20%) patients had organ-confined cancer, 60 (50%) had specimen-confined cancer, and 14 (12%) had nodal metastasis. Kaplan-Meier analysis showed overall survival rates at 5 and 10 years, respectively, of 90% and 75%, cancer-specific survival of 92% and 82%, and a PSA recurrence-free follow-up at 5 years of 31%. Using univariable analysis, preoperative PSA level, pathological Gleason score, pathological stage, surgical margin status and tumour volume were found to significantly affect the PSA recurrence-free follow-up. No variables were significant on multivariable analysis. Cancer-related symptoms were reported by only 14 patients, with a median time from surgery to first symptom of 43 months. CONCLUSION High-grade prostate cancer can be treated with RP as initial monotherapy with an acceptable 10-year cancer-specific survival (82%). The PSA recurrence-free follow-up is poor (31% at 5 years). However, few patients progress to symptomatic recurrence after PSA relapse within the first 5 years. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common cancer diagnosis in men. While often perceived as a slow, indolent malignancy, prostate cancer trails only lung cancer among cancer-related mortality in men. Current diagnosis and treatment algorithms are plagued by overdiagnosis of non-lethal indolent prostate cancer with no proven means to predict, detect, and prevent aggressive lethal prostate cancer in men most at risk. These challenges are particularly concerning for African-American men who demonstrate increased rates of prostate cancer incidence and mortality when compared to other ethnic groups. With the completion of the human genome project, technology and techniques now exist to differentiate cancer from normal tissues based on the expression patterns of thousands of genes assessed simultaneously on a single microarray gene 'chip'. This platform has greatly improved our understanding of genes that regulate tumor behavior once cancer is established. Microarrays can also be utilized in patients without cancer to determine which patients are at high risk for tumor development and in need of rational prevention strategies. Constitutional single nucleotide polymorphisms (SNPs) are one source of genetic variation and may serve as a means to identify these high-risk individuals. SNPs are single nucleotide base pair changes within a gene which occur in one percent or more of the population. SNPs can contribute to a disease state by altering the function of a protein encoded by a gene without affecting gene expression. This review will examine the current understanding of constitutional SNPs associated with prostate cancer carcinogenesis, highlight two current diagnostic array platforms and discuss implications for future prevention and screening programs. [ABSTRACT FROM AUTHOR]

Purpose: We examined the safety and potential efficacy of transrectally delivered high intensity focused ultrasound for the full gland ablation of previously untreated localized prostate cancer. Materials and Methods: A total of 20 patients with localized prostate cancer underwent 1 to 3 high intensity focused ultrasound treatments of the prostate. The primary outcome was safety and the secondary outcomes were prostate specific antigen, prostate biopsy and quality of life measures. Results: A total of 19 patients had complete followup. Serious adverse events related to treatment were limited with the most common adverse event being transient urinary retention more than 30 days in duration in only 10% of patients. Rectal injury occurred in 1 patient. With 1 to 3 treatments 42% of the patients achieved prostate specific antigen less than 0.5 ng/ml and a negative prostate biopsy. Conclusions: High intensity focused ultrasound in patients with previously untreated prostate cancer is generally well tolerated and it has the potential to completely ablate the prostate gland. With further refinement of the optimal treatment dose and technique this technology has the potential to be an effective form of therapy for localized prostate cancer. [Copyright &y& Elsevier]

The article focuses on a study on the effectiveness of combined percentage of Gleason patterns 4 and 5 in radical prostatectomy specimens in predicting cancer-specific survival among prostate cancer patients treated at Indiana University Medical Center in Indianapolis. The study analyzed various clinical and pathologic characteristics of the disease. It found that a higher combined percentage of Gleason patterns 4 and 5 was associated with older age, higher preoperative serum prostate-specific antigen level and lymph node metastasis.

Purpose: In radical prostatectomy specimens Gleason score 7 is among the most commonly assigned scores for prostate carcinoma accounting for 30% to 50% of cases. Gleason score 7 is different from other more differentiated prostate carcinomas (tumors of Gleason scores 5 and 6) with a significantly worse outcome and higher rate of recurrence. Nonetheless, Gleason score 7 tumors are heterogeneous. In this study we examined the differences in clinical outcome between primary Gleason grade 3 and 4 tumors in patients who underwent radical prostatectomy, and determined the influence of tertiary Gleason pattern 5 on patient outcome. Materials and Methods: A total of 504 patients underwent radical prostatectomy for prostate cancer and 228 of the patients (45%) had a Gleason score of 7. Cases were analyzed for a variety of clinical and pathological parameters. The influence of primary Gleason pattern and tertiary Gleason pattern 5 on patient outcome was assessed in the Cox regression model. Results: Among 228 patients with Gleason score 7 prostatic adenocarcinoma, 91 (40%) had a primary Gleason pattern 4 and 137 (60%) had primary Gleason pattern 3. Patients of the former group were more likely to have a higher pathological stage (p = 0.003), more likely to have PSA recurrence (p = 0.02) and more likely to have a tertiary Gleason pattern 5 (p <0.0001). A total of 37 (41%) patients with primary Gleason 4 had a tertiary Gleason pattern 5, whereas only 13 (9%) patients with primary Gleason 3 had a tertiary Gleason pattern 5. In the Cox regression model controlling for tumor stage and surgical margin status, the primary Gleason pattern was not an independent predictor of PSA recurrence (p = 0.80), whereas the presence of tertiary Gleason pattern 5 was a significant predictor of PSA recurrence (hazard ratio 2.10, 95% CI 1.24-3.55, p = 0.006). Five-year PSA recurrence-free survival was 70% for patients without a tertiary Gleason pattern 5 compared to 19% for those patients with a tertiary Gleason pattern 5. Conclusions: Among patients with Gleason score 7, primary Gleason grade 4 indicates a likelihood of higher tumor stage and higher probability of PSA recurrence than does primary pattern 3. However, it does not independently predict a worse outcome after controlling for other known prognostic parameters associated with disease progression. Regardless of whether the primary Gleason pattern is 3 or 4, a tertiary Gleason pattern 5 is the strongest predictor of a worse outcome in patients with Gleason grade 7 prostatic adenocarcinoma. Therefore, tertiary pattern 5 should be reported in radical prostatectomy specimens. [Copyright &y& Elsevier]

OBJECTIVE To analyse tumour extent as a predictor of cancer progression after radical prostatectomy (RP), using a multivariate Cox regression model, as several variables (e.g. Gleason grade and tumour stage) are well-established prognostic factors in prostate cancer but it is uncertain if the visual estimation of tumour extent (percentage of carcinoma) is an independent predictor for prostate cancer recurrence. PATIENTS AND METHODS Tumour extent was estimated in the RP specimens from 504 men with clinically localized prostate cancer; clinical follow-up data were available for 459 men. The mean (range) follow-up was 44.3 (1.5–144) months. Cancer progression was defined by the development of biochemical recurrence, local recurrence, or distant metastasis. Multivariate analysis was used to assess tumour extent as a predictor of cancer progression. RESULTS Of the 459 patients, 157 had cancer progression; the mean tumour extent was 36% and 24% in those with and without cancer progression, respectively ( P < 0.001). Univariate analysis showed a significant association between the visual estimation of tumour extent and tumour stage, Gleason grade, surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis, and preoperative serum prostate-specific antigen level (all P < 0.001). However, in a multivariate Cox regression model controlling for pathological stage, Gleason score, and surgical margin status, the visual estimation of tumour extent was no longer a significant predictor of cancer progression ( P = 0.84). CONCLUSION The visual estimation of tumour extent was associated with various established prognostic factors for prostate cancer, and with cancer progression in a univariate analysis, but it was not a significant predictor of cancer progression in the multivariate analysis controlling for pathological stage, Gleason score, and surgical margin status. [ABSTRACT FROM AUTHOR]

OBJECTIVE To test the hypothesis that prostate cancer patients with clinical stage cT1c and cT2 have similar outcomes and clinicopathological features, and should be grouped together. PATIENTS AND METHODS From a series of men with prostate cancer who had a radical retropubic prostatectomy (RP), we assessed those with cT1c (223) and cT2 (65) adenocarcinoma. All RP specimens were totally embedded and whole-mounted; tumour volume was measured using the grid method. Clinical and pathological characteristics were analysed. RESULTS Patients with cT2 tumours were more likely to have a higher Gleason score ( P = 0.04) and final pathological stage ( P = 0.05) than those with cT1c tumours. There was no significant difference in age ( P = 0.92), preoperative PSA level ( P = 0.17), prostate weight ( P = 0.34), tumour volume ( P = 0.16), surgical margin status ( P = 0.86), multifocality ( P = 0.92), the presence of perineural invasion ( P = 0.09), or high-grade prostatic intraepithelial neoplasia ( P = 0.99) between patients with clinical stage cT1c and those with cT2 tumours. There was no difference in PSA recurrence between patients with clinical stage T1c and those with cT2 tumours ( P = 0.27). CONCLUSIONS Patients with clinical stage cT2 tumours have a higher Gleason score and advanced pathological stage than tumours detected because of a high serum PSA level (cT1c). These results suggest that clinical stage cT1c tumours should be separated from clinical stage cT2 disease, but the PSA recurrence rate for both tumour stages is similar, indicating a need for further evaluation and refinement of the current clinical staging system. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging-guided transurethral ultrasound ablation (TULSA) of the prostate uses ultrasound to thermally coagulate tissue under real-time MRI guidance. Real-time feedback from closed-loop MRI thermometry automatically controls treatment parameters to match tissue response in the prescribed ablation volume. The pivotal study of TULSA ("TACT", NCT02766543), which included a low- to intermediate-risk prostate cancer (PCa) population, has reached the end of the 5-year follow-up duration. Here we report the safety and efficacy outcomes at 5 years The TACT study enrolled 115 patients across 13 sites in 5 countries. Eligibility criteria included stage ≤ T2b, PSA ≤ 15 ng/mL, and Grade Group (GG) 1-2 disease. The protocol prescribed a single whole-gland TULSA treatment sparing the prostatic urethra and urinary sphincter, and repeat TULSA was not allowed. The primary endpoints were PSA reduction and adverse events, both assessed at 1 year. Histologic control on 10-core biopsy, and prostate volume reduction on multiparametric MRI (mpMRI) were also assessed at 1 year. Other secondary endpoints, assessed to 5 years, included adverse events, quality of life, PSA, and the rate of salvage treatment. Baseline (median [IQR]) age and PSA were 65 (59-69) years and 6.3 (4.6-7.9) ng/mL, with ≥GG2 disease in 72/115 men. At 1y, median prostate volume decreased from 37.3 to 2.8 cc (92%); 94/111 (85%) were free of ≥GG2 disease. By 5y, median (IQR) PSA decreased to 0.6 (0.18-1.9) ng/mL (n=68); 25 (21.7%) received salvage treatment (10 prostatectomy, 11 radiotherapy, 3 ADT, 1 surgery+radiation) without unexpected complications. Early predictors of treatment failure by 5 years included 1y PSA (OR=3; CI[1.7,5.4]) and visible lesion on 1y mpMRI (OR=12; CI[4.4,34]) (both p≤0.001). Failure modes include undertreatment due to patient selection or targeting error, and misalignment caused by intraprocedural swelling/motion. By 5 years, 61/66 (92%) recovered pad-free continence; 80/92 (87%) preserved erections sufficient for penetration. Grade 3 adverse events occurred in 12 men (10%), with no Grade≥4 event or rectal injury. Effective disease control is durable to 5 years after a single TULSA procedure, with a favorable safety profile. Favorable preservation of genitourinary quality of life is also durable to 5 years. Treatment failure modes include screening and intraprocedural factors. While the pivotal study represents early experience with TULSA, the risk of failure is mitigated by modern protocols. Such protocols include best practices for screening for intraprostatic calcifications that can lead to undertreatment, refined strategies for device positioning, and thermal dose escalation to address undertreatment that is visible on intraprocedural imaging. Factors from intraprocedural imaging and early clinical follow-up can predict salvage therapy by 5 years. [ABSTRACT FROM AUTHOR]

Introduction This study was performed to estimate the human radiation dosimetry for [ 68 Ga]Ga-HBED-CC (PSMA-11) ( 68 Ga PSMA-11). Methods Under an RDRC-approved research protocol, we evaluated the biodistribution and pharmacokinetics of 68 Ga PSMA-11 with serial PET imaging following intravenous administration to nine prostate cancer patients in whom clinical [ 11 C]acetate PET/CT exams had been independently performed under Expanded Access IND 118,204. List-mode imaging was performed over the initial 0–10 min post-injection with the pelvis in the field-of-view. Whole-body images were acquired, pelvis-to-head, at 15, 60, and 90-min post-injection. Additional images of the pelvis were acquired at 40-min and 115-min, and voided urine collected from each subject at 48-min and 120-min post-injection. Radiation dosimetry estimates were calculated from these data using the OLINDA software package. Results Renal uptake was high and relatively invariant, ranging from 11% to 14% of the injected dose between 15 and 90-min post-injection. Radioactivity collected in the voided urine accounted for 14% of the injected dose over a period of 120-min. Lymph nodes and skeletal metastases suspicious for prostate cancer recurrence were detected in a greater number of patients using 68 Ga PSMA-11 than using 11 C-acetate. Conclusion Kidneys are the critical organ following 68 Ga PSMA-11 administration, receiving an estimated dose of 0.413 mGy/MBq. Advances in knowledge and implications for patient care This study confirms that the kidneys will be the critical organ following intravenous administration of 68 Ga PSMA-11, and provided data consistent with the expectation that 68 Ga PSMA-11 will be superior to [ 11 C]acetate for defining sites of recurrence in prostate cancer patients presenting with biochemical relapse. [ABSTRACT FROM AUTHOR]

Background: Incontinence and impotence occur following radical prostatectomy due to injury to nerves and sphincter muscle. Preserving nerves and muscle adjacent to prostate cancer risks positive surgical margins. Advanced imaging with MRI has improved cancer localization but limitations exist.Objective: To measure the accuracy for assessing extra-prostatic extension at nerve bundles for 2 PSMA-PET tracers and to compare the PET accuracy to standard-of-care predictors including MRI and biopsy results.Materials and Methods: We studied men with PSMA-targeted PET imaging, performed prior to prostatectomy in men largely with intermediate to high-risk prostate cancer, and retrospectively evaluated for assessment of extra-prostatic extension with whole-mount analysis as reference standard. Two different PSMA-PET tracers were included: 68Ga-PSMA-11 and 68Ga-P16-093. Blinded reviews of the PET and MRI scans were performed to assess extra-prostatic extension (EPE). Sensitivity and specificity for extra-prostatic extension were compared using McNemar's Chi2.Results: Pre-operative PSMA-PET imaging was available for 71 patients with either 68Ga-P16-093 (n = 25) or 68Ga-PSMA-11 (n = 46). There were 24 (34%) with pT3a (EPE) and 16 (23%) with pT3b (SVI). EPE Sensitivity (87% vs. 92%), Specificity (77% vs. 76%), and ROC area (0.82 vs. 0.84) were similar between P16-093 and PSMA-11, respectively (P = 0.87). MRI (available in only 45) found high specificity (83%) but low sensitivity (60%) for EPE when using a published grading system. MRI sensitivity was significantly lower than the PSMA-PET (60% vs. 90%, P = 0.02), but similar to PET when using a >5 mm capsular contact (76% vs. 90%, P = 0.38). A treatment change to "nerve sparing" was recommended in 21 of 71 (30%) patients based on PSMA-PET imaging.Conclusions: Presurgical PSMA-PET appeared useful as a tool for surgical planning, changing treatment plans in men with ≥4+3 or multi-core 3+4 prostate cancer resulting in preservation of nerve-bundles. [ABSTRACT FROM AUTHOR]

Development of methods for rapid distinction between cancerous and non-neoplastic tissues is an important goal in disease diagnosis. To this end, desorption electrospray ionization mass spectrometiy (DESI-MS) imaging was applied to analyze the lipid profiles of thin tissue sections of 68 samples of human prostate cancer and normal tissue. The disease state of the tissue sections was determined by independent histopathological examination. Cholesterol sulfate was identified as a differentiating compound, found almost exclusively in cancerous tissues including tissue containing precancerous lesions. The presence of cholesterol sulfate in prostate tissues might serve as a tool for prostate cancer diagnosis although confirmation through larger and more diverse cohorts and correlations with clinical outcome data is needed. [ABSTRACT FROM AUTHOR]

Objectives To assess urinary quality-of-life (QoL) and oncologic outcomes between wide resection (WR) robot-assisted laparoscopic radical prostatectomy (RALP) and non-WR (NWR) RALP in men with intermediate- or high-risk (Cancer of the Prostate Risk Assessment [CAPRA]-9 >2) prostate adenocarcinoma. Methods Patients undergoing RALP (2004–2013) for intermediate- or high-risk prostate adenocarcinoma were analyzed. Kaplan-Meier methodology with Cox proportional hazards regression evaluated biochemical recurrence–free survival (BCR-FS). Multiple logistic regression was used to determine the relationship between (1) WR with positive surgical margins (+SM) and (2) WR with posterolateral+SM after adjusting for demographics and CAPRA-9 score. University of California, Los Angeles-Prostate Cancer Index and Extended Prostate Cancer Index Composite questionnaires assessed urinary QoL. Multiple mixed-effects linear regression adjusting for demographics and CAPRA-9 evaluated differences in QoL between WR and NWR. Results A total of 483 RALP cases met inclusion criteria—129 (26.7%) underwent WR and 354 (73.3%) underwent NWR-RALP. There were no demographic differences between groups. Burden of disease was greater in patients undergoing WR ( P <0.001). There was no difference in+SM rates between WR and NWR ( P = 0.505). Adjusting for demographics and CAPRA-9 score, WR patients had a clinically relevant 27% decrease in posterolateral+SM (odds ratio = 0.73; 95% CI: 0.38–1.41; P = 0.351). WR was not associated with worse BCR-FS (hazard ratio = 1.24; 95% CI: 0.83–1.86, P = 0.30). Adjusting for pathology, University of California, Los Angeles and Extended Prostate Cancer Index Composite urinary domain scores were similar between WR and NWR groups. Conclusion Despite WR patients having worse clinical disease, WR-RALP can be performed with minimal detriment to BCR-FS and urinary QoL. The greater incidence of occult metastasis in higher risk patients may make surgical technique a nonsignificant factor. Nevertheless, WR remains a reasonable option for complete surgical excision. [ABSTRACT FROM AUTHOR]