Anne-Maree Haynes

Superior Quality of Life and Improved Surgical Margins Are Achievable with Robotic Radical Prostatectomy After a Long Learning Curve: A Prospective Single-surgeon Study of 1552 Consecutive Cases

BACKGROUND Comparative studies suggest functional and perioperative superiority of robot-assisted radical prostatectomy (RARP) over open radical prostatectomy (ORP). OBJECTIVE To determine whether high-volume experienced open surgeons can improve their functional and oncologic outcomes with RARP and, if so, how many cases are required to surpass ORP outcomes and reach the learning curve plateau. DESIGN, SETTING, AND PARTICIPANTS A prospective observational study compared two surgical techniques: 1552 consecutive men underwent RARP (866) or ORP (686) at a single Australian hospital from 2006 to 2012, by one surgeon with 3000 prior ORPs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Demographic and clinicopathologic data were collected prospectively. The Expanded Prostate Cancer Index Composite quality of life (QoL) questionnaire was administered at baseline, 1.5, 3, 6, 12, and 24 mo. Multivariate linear and logistic regression modelled the difference in QoL domains and positive surgical margin (PSM) odds ratio (OR), respectively, against case number. RESULTS AND LIMITATIONS A total of 1511 men were included in the PSM and 609 in the QoL analysis. RARP sexual function scores surpassed ORP scores after 99 RARPs and increased to a mean difference at 861st case of 11.0 points (95% confidence interval [CI], 5.9-16.1), plateauing around 600-700 RARPs. Early urinary incontinence scores for RARP surpassed ORP after 182 RARPs and increased to a mean difference of 8.4 points (95% CI, 2.1-14.7), plateauing around 700-800 RARPs. The odds of a pT2 PSM were initially higher for RARP but became lower after 108 RARPs and were 55% lower (OR: 0.45; 95% CI, 0.22-0.92) by the 866th RARP. The odds of a pT3/4 PSM were initially higher for RARP but decreased, plateauing around 200-300 RARPs with an OR of 1.15 (0.68-1.95) at the 866th RARP. Limitations include single-surgeon data and residual confounding. CONCLUSIONS RARP had a long learning curve with inferior outcomes initially, and then showed progressively superior sexual, early urinary, and pT2 PSM outcomes and similar pT3 PSM and late urinary outcomes. Learning RARP was worthwhile for this high-volume surgeon, but the learning curve may not be justifiable for late-career/low-volume surgeons; further studies are needed.

Prognostic significance of Gleason pattern in patients with Gleason score 7 prostate carcinoma

In the current study, the authors sought to further stratify the prognosis of patients with Gleason score (GS) 7 prostate carcinoma. They assessed the influence on outcome of a predominant poorly differentiated Gleason pattern (primary Gleason pattern [GP] 4) and/or a coincident small focus of poorly differentiated tumor of higher grade (tertiary GP 5).

Should experienced open prostatic surgeons convert to robotic surgery? The real learning curve for one surgeon over 3 years

Study Type – Therapy (case series)
Level of Evidence 4

Prognostic Significance of Pathologic Features in Localized Prostate Cancer Treated With Radical Prostatectomy: Implications for Staging Systems and Predictive Models

PURPOSE Although predicting outcome for men with clinically localized prostate cancer (PC) has improved, the staging system and nomograms used to do this are based on results from the North American health system. To be internationally applicable, these models require testing in cohorts from a variety of different health systems based on the predominant PC case identification methods used. PATIENTS AND METHODS We studied 732 men with localized PC treated with radical prostatectomy and no preoperative therapy between 1986 and 1999 at one Australian institution to determine the effect of clinicopathologic features on disease-free survival. RESULTS Preoperative serum prostate-specific antigen (PSA) concentration, Gleason score, pathologic stage, and year of surgery were independent predictors of outcome. Although margin status demonstrated only a trend toward significance in multivariate modeling overall, it proved to be independent in subgroups based on later year of surgery (1986 to 1994 v 1995 to 1998), preoperative PSA of less than 10 ng/mL, and Gleason score > or = 7. Adjuvant radiation therapy improved disease-free survival rates in patients with multiple surgical margin involvement. CONCLUSION This work confirms the prognostic significance of pathologic stage, Gleason score, and preoperative serum PSA. In the context of a contemporaneous screening effect in Australia, these findings may have implications for methods that predict outcome following surgery as screening becomes more prevalent in a population. The independent prognostic effect of margin status may alter with an increase in the proportion of screening-identified PCs. Staging systems and nomograms that predict outcome following surgery require validation in cohorts with different health practices before being universally applied.

High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy.

Study Type – Prognosis (case series)

Outcomes of transperineal template-guided prostate biopsy in 409 patients

With an aging population and routine use of PSA testing, there is an increase in men undergoing biopsy to assess for prostate cancer. The most common route for accessing the prostate is through the rectum, which potentially exposes the patient to otherwise innocuous Enterobacteriaceae. The rising incidence of extended‐spectrum beta‐lactamase has been linked to a rise in post‐TRUS biopsy infection rates internationally. The study describes an alternative route for biopsy of the prostate that is associated with a very low infection rate, whilst still maintaining a good tumour detection rate.

Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers

Background: Previously, we showed that gene suppression commonly occurs across chromosome 2q14.2 in colorectal cancer, through a process of long-range epigenetic silencing (LRES), involving a combination of DNA methylation and repressive histone modifications. We now investigate whether LRES also occurs in prostate cancer across this 4-Mb region and whether differential DNA methylation of 2q14.2 genes could provide a regional panel of prostate cancer biomarkers. Methods: We used highly sensitive DNA methylation headloop PCR assays that can detect 10 to 25 pg of methylated DNA with a specificity of at least 1:1,000, and chromatin immunoprecipitation assays to investigate regional epigenetic remodeling across 2q14.2 in prostate cancer, in a cohort of 195 primary prostate tumors and 90 matched normal controls. Results: Prostate cancer cells exhibit concordant deacetylation and methylation of histone H3 Lysine 9 (H3K9Ac and H3K9me2, respectively), and localized DNA hypermethylation of EN1, SCTR, and INHBB and corresponding loss of H3K27me3. EN1 and SCTR were frequently methylated (65% and 53%, respectively), whereas INHBB was less frequently methylated. Conclusions: Consistent with LRES in colorectal cancer, we found regional epigenetic remodeling across 2q14.2 in prostate cancer. Concordant methylation of EN1 and SCTR was able to differentiate cancer from normal (P < 0.0001) and improved the diagnostic specificity of GSTP1 methylation for prostate cancer detection by 26%. Impact: For the first time we show that DNA methylation of EN1 and SCTR promoters provide potential novel biomarkers for prostate cancer detection and in combination with GSTP1 methylation can add increased specificity and sensitivity to improve diagnostic potential. Cancer Epidemiol Biomarkers Prev; 20(1); 148–59. ©2011 AACR.

Medium-term oncological outcomes for extended vs saturation biopsy and transrectal vs transperineal biopsy in active surveillance for prostate cancer.

To assess, in men undergoing active surveillance (AS) for low‐risk prostate cancer, whether saturation or transperineal biopsy altered oncological outcomes, compared with standard transrectal biopsy.

The impact of nerve sparing on incidence and location of positive surgical margins in radical prostatectomy

Study Type – Therapy (case series)

A multiparametric magnetic resonance imaging-based risk model to determine the risk of significant prostate cancer prior to biopsy

To develop and externally validate a predictive model for detection of significant prostate cancer.