Study Type – Therapy (case series)
Level of Evidence 4 OBJECTIVE To critically analyse the learning curve for one experienced open surgeon converting to robotic surgery for radical prostatectomy (RP). PATIENTS AND METHODS From February 2006 to December 2008, 502 patients had retropubic RP (RRP) while concurrently 212 had robot‐assisted laparoscopic RP (RALP) by one urologist. We prospectively compared the baseline patient and tumour characteristics, variables during and after RP, histopathological features and early urinary functional outcomes in the two groups. RESULTS The patients in both groups were similar in age, preoperative prostate‐specific antigen level, and prostatic volume. However, there were more high‐stage (T2b and T3, P= 0.02) and ‐grade (Gleason 9, P= 0.01) tumours in the RRP group. The mean (range) operative duration was 147 (75–330) min for RRP and 192 (119–525) min for RALP (P < 0.001); 110 cases were required to achieve ‘3‐h proficiency’. Major complication rates were 1.8% and 0.8% for RALP and RRP, respectively. The overall positive surgical margin (PSM) rate was 21.2% in the RALP and 16.7% in the RRP group (P= 0.18). PSM rates for pT2 were comparable (11.6% vs 10.1%, P= 0.74). pT3 PSM rates were higher for RALP than RRP (40.5% vs 28.8%, P= 0.004). The learning curve started to plateau in the overall PSM rate after 150 cases. For the pT2 and pT3 PSM rates, the learning curve tended to flatten after 140 and 170 cases, respectively. The early continence rates were comparable (P= 0.07) but showed a statistically significant improvement after 200 cases. CONCLUSIONS Our analysis of the learning curve has shown that certain components of the curve for an experienced open surgeon transferring skills to the robotic platform take different times. We suggest that patient selection is guided by these milestones, to maximize oncological outcomes.

Purpose-To assess the feasibility of luminal water imaging (LWI), a quantitative T 2 -based MRI technique, for the detection and grading of prostatic cancer (PCa).Material and Methods-18 patients with biopsy proven PCa provided informed consent to be included in this institutional human ethics board approved prospective study between January 2015, and January 2016. Patients underwent 3T MRI shortly before radical prostatectomy. T 2 distributions were generated with regularized Non-Negative Least Squares (NNLS)algorithm from multi-echo spin echo MRI data. From T 2 distributions, maps of seven MR parameters: N comp , T 2-short , T 2-long , geometric mean T 2 (gmT 2 ), Luminal Water Fraction (LWF), A short , and A long were generated and compared with digitized images of Hematoxylin and Eosin (H&E) stained whole-mount histology sections. Paired-t-test determined significant differences between MR parameters in malignant and non-malignant tissue. Correlation with Gleason score (GS) was evaluated with Spearman's rank correlation test. Diagnostic accuracy was evaluated using logistic generalized linear mixed effect models (GLMMs) and receiver operating characteristic (ROC) analysis. Results-The average values of four MR parameters: gmT 2 , A short , A long , and LWF were significantly different between malignant and non-malignant tissue. All MR parameters except for T 2-long showed significant correlation (P<0.05) with GS in peripheral zone (PZ). The highest correlation with GS was obtained for LWF (−0.78 ± 0.11, p < 0.001

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Only 30–35% of patients with positive surgical margins after radical prostatectomy develop recurrent disease. Adjuvant radiotherapy reduces the rate of biochemical relapse or metastasis and improves overall survival after radical prostatectomy. Various pathological factors, such as location and extent of positive margins, have been proposed as possible prognostic factors in men with margin‐positive prostate cancer, however, the recent International Society of Urological Pathology consensus meeting in Boston noted that there is limited data on the significance of Gleason grade of the carcinoma at a positive margin. The present study shows that the presence of high grade prostate cancer, i.e. Gleason pattern 4 or 5, at a positive surgical margin is an independent predictor of biochemical recurrence after radical prostatectomy. Moreover, patients with lower grade carcinoma at the margin have a similar prognosis to men with negative margins. Hence, assessment of Gleason grade at the site of positive margin may aid optimal selection of patients for adjuvant radiotherapy. OBJECTIVE To establish predictors of biochemical recurrence by analysing the pathological characteristics of positive surgical margins (PSMs), including Gleason grade of the carcinoma at the involved margin. PATIENTS AND METHODS Clinicopathological and outcome data on 940 patients who underwent radical prostatectomy (RP) between 1997 and 2003 were collected. Of these, 285 (30.3%) patients with PSMs were identified for pathological review, including assessment of location of margin, linear extent, number of PSMs, plane of margin and Gleason grade (3 vs 4 or 5) at the margin. RESULTS At a median follow‐up of 82 months, the biochemical recurrence rate of the PSM cohort was 29%. On univariate analysis, the presence of Gleason grade 4 or 5 at the margin (34.4% of cases) was significantly associated with biochemical recurrence (hazard ratio [HR] 2.80, 95% confidence interval [CI]= 1.82–4.32, P < 0.001) compared with the presence of Gleason grade 3. Linear extent of margin involvement was also associated with recurrence (P= 0.009). Single vs multiple margin involvement, location, and plane of the involved margin were not significant predictors of recurrence. On multivariate analysis, Gleason grade 4 or 5 at the margin remained an independent predictor of recurrence (HR 2.14, 95% CI = 1.29–4.03, P= 0.003). CONCLUSION The Gleason grade at the site of a PSM identifies patients at increased risk of biochemical recurrence and should aid stratification of patients for adjuvant radiation therapy.

Purpose-To determine the relationship between parameters measured from luminal water imaging (LWI), a new MRI T 2 mapping technique, and the corresponding tissue composition in prostate.Material and Methods-17 patients with prostate cancer were examined with a 3D multi-echo spin echo sequence at 3T prior to undergoing radical prostatectomy. Maps of seven MR parameters, called N, T 2-short , T 2-long , A short , A long , geometric mean T 2 time (gmT 2 ), and luminal water fraction (LWF), were generated using non-negative least squares (NNLS) analysis of the T 2 decay curves. MR parametric maps were correlated to digitized whole-mount histology sections. Percentage area of tissue components, including luminal space, nuclei, and cytoplasm plus stroma, was measured on the histology sections by using color-based image segmentation. Spearman's rank correlation test was used to evaluate the correlation between MR parameters and the corresponding tissue components, with particular attention paid to the correlation between LWF and percentage area of luminal space.Results-N, T 2-short , A long , gmT 2 , and LWF showed significant correlation (P<0.05) with percentage area of luminal space and stroma plus cytoplasm. T 2-short , and gmT 2 also showed significant correlation (P<0.05) with percentage area of nuclei. Overall, the strongest correlation was observed between LWF and luminal space (Spearman's coefficient of rank correlation=0.75, p < 0.001).

Background:Increasing evidence supporting the role of immune checkpoint blockade in cancer management has been bolstered by recent reports demonstrating significant and durable clinical responses across multiple tumour types, including metastatic urothelial carcinoma (mUC). The majority of these results are achieved via blockade of the programmed death (PD) axis, which like CTLA-4 blockade permits T-cell activation and immune-mediated anti-tumour activity- essentially harnessing the patient’s own immune system to mount an anti-neoplastic response. However, while clinical responses can be striking, our understanding of the biology of immune checkpoint blockade is only beginning to shed light on how to maximize and even improve patient outcomes with immune checkpoint blockade, especially in UC.Methods:We performed a literature review for immune checkpoint blockade with a focus on rationale for checkpoint therapy and outcomes in UC. We also highlight the advances made in other tumour types, with a focus on the recent 2015 meeting of the American Society for Clinical Oncology.Results:In heavily pre-treated UC, trials are suggesting objective response rates above 30% . These impressive results are seen across multiple different tumour types, especially those with high burden of DNA level mutations. Identification of prognostic biomarkers is currently under investigation, in order to improve patient selection. Interestingly, response to PD-1 directed therapy is seen even in patients with no evidence of PD-1 positivity on immunohistochemistry. This has led to the development of enhanced biomarkers including assessing DNA mutation rates and immune gene signatures, to improve patient selection.Conclusions:Immune checkpoint blockade is an exciting cancer treatment modality which is demonstrating impressive clinical results across multiple tumour types. For UC, anti-PD directed therapy represents a much needed treatment in the metastatic, post chemotherapy context. Potential for these agents to have clinical utility in non-metastatic UC is still to be assessed.