Summary Background The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and ...overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone. Methods The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50–69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers PSA, free PSA, intact PSA, hK2, MSMB, MIC1, genetic polymorphisms 232 SNPs, and clinical variables age, family, history, previous prostate biopsy, prostate exam), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com , number ISRCTN84445406. Findings The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (p<0·0001), the area under the curve was 0·56 (95% CI 0·55–0·60) with PSA alone and 0·74 (95% CI 0·72–0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (p<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of ≥3 ng/mL to diagnose high risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI 24–39) and could avoid 44% (35–54) of benign biopsies. Interpretation The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes. Funding Stockholm County Council (Stockholms Läns Landsting).
Abstract Context Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) have gained popularity. ...Objective To report a systematic literature review and cumulative analysis of perioperative outcomes and complications of RARC in comparison with ORC and LRC. Evidence acquisition Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy . RARC case series and studies comparing RARC with either ORC or LRC were collected. Cumulative analysis was conducted. Evidence synthesis The searches retrieved 105 papers. According to the different diversion type, overall mean operative time ranged from 360 to 420 min. Similarly, mean blood loss ranged from 260 to 480 ml. Mean in-hospital stay was about 9 d for all diversion types, with consistently high readmission rates. In series reporting on RARC with either extracorporeal or intracorporeal conduit diversion, overall 90-d complication rates were 59% (high-grade complication: 15%). In series reporting RARC with intracorporeal continent diversion, the overall 30-d complication rate was 45.7% (high-grade complication: 28%). Reported mortality rates were ≤3% for all diversion types. Comparing RARC and ORC, cumulative analyses demonstrated shorter operative time for ORC, whereas blood loss and in-hospital stay were better with RARC (all p values <0.003). Moreover, 90-d complication rates of any-grade and 90-d grade 3 complication rates were lower for RARC (all p values <0.04), whereas high-grade complication and mortality rates were similar. Conclusions RARC can be performed safely with acceptable perioperative outcome, although complications are common. Cumulative analyses demonstrated that operative time was shorter with ORC, whereas RARC may provide some advantages in terms of blood loss and transfusion rates and, more limitedly, for postoperative complication rates over ORC and LRC. Patient summary Although open radical cystectomy (RC) is still regarded as a standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RC are becoming more popular. Robotic RC can be safely performed with acceptably low risk of blood loss, transfusion, and intraoperative complications; however, as for open RC, the risk of postoperative complications is high, including a substantial risk of major complication and reoperation.
Abstract Context Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly performed. ...Objective To report on a systematic literature review and cumulative analysis of pathologic, oncologic, and functional outcomes of RARC in comparison with ORC and LRC. Evidence acquisition Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy . RARC case series and studies comparing RARC with either ORC or LRC were collected. A cumulative analysis was conducted. Evidence synthesis The searches retrieved 105 papers, 87 of which reported on pathologic, oncologic, or functional outcomes. Most series were retrospective and had small case numbers, short follow-up, and potential patient selection bias. The lymph node yield during lymph node dissection was 19 (range: 3–55), with half of the series following an extended template (yield range: 11–55). The lymph node–positive rate was 22%. The performance of lymphadenectomy was correlated with surgeon and institutional volume. Cumulative analyses showed no significant difference in lymph node yield between RARC and ORC. Positive surgical margin (PSM) rates were 5.6% (1–1.5% in pT2 disease and 0–25% in pT3 and higher disease). PSM rates did not appear to decrease with sequential case numbers. Cumulative analyses showed no significant difference in rates of surgical margins between RARC and ORC or RARC and LRC. Neoadjuvant chemotherapy use ranged from 0% to 31%, with adjuvant chemotherapy used in 4–29% of patients. Only six series reported a mean follow-up of >36 mo. Three-year disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates were 67–76%, 68–83%, and 61–80%, respectively. The 5-yr DFS, CSS, and OS rates were 53–74%, 66–80%, and 39–66%, respectively. Similar to ORC, disease of higher pathologic stage or evidence of lymph node involvement was associated with worse survival. Very limited data were available with respect to functional outcomes. The 12-mo continence rates with continent diversion were 83–100% in men for daytime continence and 66–76% for nighttime continence. In one series, potency was recovered in 63% of patients who were evaluable at 12 mo. Conclusions Oncologic and functional data from RARC remain immature, and longer-term prospective studies are needed. Cumulative analyses demonstrated that lymph node yields and PSM rates were similar between RARC and ORC. Conclusive long-term survival outcomes for RARC were limited, although oncologic outcomes up to 5 yr were similar to those reported for ORC. Patient summary Although open radical cystectomy (RC) is still regarded as the standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RCs are becoming more popular. Templates of lymph node dissection, lymph node yields, and positive surgical margin rates are acceptable with robot-assisted RC. Although definitive comparisons with open RC with respect to oncologic or functional outcomes are lacking, early results appear comparable.
The telomerase reverse transcriptase (TERT) promoter, an important element of telomerase expression, has emerged as a target of cancer-specific mutations. Originally described in melanoma, the ...mutations in TERT promoter have been shown to be common in certain other tumor types that include glioblastoma, hepatocellular carcinoma, and bladder cancer. To fully define the occurrence and effect of the TERT promoter mutations, we investigated tumors from a well-characterized series of 327 patients with urothelial cell carcinoma of bladder. The somatic mutations, mainly at positions −124 and −146 bp from ATG start site that create binding motifs for E-twenty six/ternary complex factors (Ets/TCF), affected 65.4% of the tumors, with even distribution across different stages and grades. Our data showed that a common polymorphism rs2853669, within a preexisting Ets2 binding site in the TERT promoter, acts as a modifier of the effect of the mutations on survival and tumor recurrence. The patients with the mutations showed poor survival in the absence hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.02–4.70 but not in the presence (HR 0.42, 95% CI 0.18–1.01) of the variant allele of the polymorphism. The mutations in the absence of the variant allele were highly associated with the disease recurrence in patients with Tis, Ta, and T1 tumors (HR 1.85, 95% CI 1.11–3.08). The TERT promoter mutations are the most common somatic lesions in bladder cancer with clinical implications. The association of the mutations with patient survival and disease recurrence, subject to modification by a common polymorphism, can be a unique putative marker with individualized prognostic potential.
Abstract Background Robot-assisted laparoscopic radical prostatectomy (RALP) has become widely used without high-grade evidence of superiority regarding long-term clinical outcomes compared with open ...retropubic radical prostatectomy (RRP), the gold standard. Objective To compare patient-reported urinary incontinence and erectile dysfunction 12 mo after RALP or RRP. Design, setting, and participants This was a prospective, controlled, nonrandomised trial of patients undergoing prostatectomy in 14 centres using RALP or RRP. Clinical-record forms and validated patient questionnaires at baseline and 12 mo after surgery were collected. Outcome measurements and statistical analyses Odds ratios (ORs) were calculated with logistic regression and adjusted for possible confounders. The primary end point was urinary incontinence (change of pad less than once in 24 h vs one time or more per 24 h) at 12 mo. Secondary end points were erectile dysfunction at 12 mo and positive surgical margins. Results and limitations Of 2625 eligible men, 2431 (93%) could be evaluated for the primary end point. At 12 mo after RALP, 366 men (21.3%) were incontinent, as were 144 (20.2%) after RRP. The adjusted OR was 1.08 (95% confidence interval CI, 0.87–1.34). Erectile dysfunction was observed in 1200 men (70.4%) 12 mo after RALP and 531 (74.7%) after RRP. The adjusted OR was 0.81 (95% CI, 0.66–0.98). The frequency of positive surgical margins did not differ significantly between groups: 21.8% in the RALP group and 20.9% in the RRP group (adjusted OR: 1.09; 95% CI, 0.87–1.35). The nonrandomised design is a limitation. Conclusions In a Swedish setting, RALP for prostate cancer was modestly beneficial in preserving erectile function compared with RRP, without a statistically significant difference regarding urinary incontinence or surgical margins. Patient summary We compared patient-reported urinary incontinence after prostatectomy with two types of surgical technique. There was no statistically significant improvement in the rate of urinary leakage, but there was a small improvement regarding erectile function after robot-assisted operation.
To investigate the reliability with which healthcare professionals with different levels of expertise are able to impart the exact location of prostate cancer (PCA) after (A) reading written magnetic ...resonance imaging (MRI) reports, (B) attending MRI presentations in multidisciplinary team meetings (MDT), and (C) examining 3D printed prostate models, which represents a new technology to describe the location of PCA lesions.
We used three different PCA cases to assess the three information tools. Construct validation was performed using two healthcare groups with different levels of expertise: (1) Nine expert urologists in PCA, and (2) nine medical students. After each information tool, the study participants plotted the tumor location in a 2-dimensional prostate diagram. A scoring system was established to evaluate the drawings in terms of accuracy of plotting tumor position. Data are shown as median scores with interquartile range.
Within the expert group, no significant difference was seen in the overall scoring results between the information tools (p = 0.34). Medical students performed significantly worse with MDT information (p = 0.03). Experts performed better in all three information tools compared to students, resulting in a significantly 25% higher overall total score (25.022.3-26.7 vs. 20.015.0-24.0, p<0.001). The difference was largest after MDT information, with experts showing a 49% better scoring (p<0.001), and second largest with the 3D printed models, showing a 17% better scoring of the experts (p = 0.07). No difference was found in the written MRI report scoring results between experts and students.
3D printed models provided better orientation guide to medical students compared to MDT MRI presentations. This indicates that the 3D printed models might be easier to understand than the current gold standard MDT conferences. Therefore, 3D models may play an increasingly important role in providing guidance for orientation for less experienced individuals, such as surgical trainees.
Abstract Background Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, ...8–10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3 + 4 = 7 and 4 + 3 = 7 are often considered the same prognostic group. Objective To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data. Design, setting, and participants Between 2005 and 2014, 20 845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions. Outcome measurements and statistical analysis Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores. Results and limitations In the surgery cohort, we found large differences in recurrence rates between both Gleason 3 + 4 versus 4 + 3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3 + 4, 4 + 3, 8, and 9–10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five–grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death. Conclusions The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. Patient summary We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.
Abstract Context Radical prostatectomy (RP) approaches have rarely been compared adequately with regard to margin and perioperative complication rates. Objective Review the literature from 2002 to ...2010 and compare margin and perioperative complication rates for open retropubic RP (ORP), laparoscopic RP (LRP), and robot-assisted LRP (RALP). Evidence acquisition Summary data were abstracted from 400 original research articles representing 167 184 ORP, 57 303 LRP, and 62 389 RALP patients (total: 286 876). Articles were found through PubMed and Scopus searches and met a priori inclusion criteria (eg, surgery after 1990, reporting margin rates and/or perioperative complications, study size >25 cases). The primary outcomes were positive surgical margin (PSM) rates, as well as total intra- and perioperative complication rates. Secondary outcomes included blood loss, transfusions, conversions, length of hospital stay, and rates for specific individual complications. Weighted averages were compared for each outcome using propensity adjustment. Evidence synthesis After propensity adjustment, the LRP group had higher positive surgical margin rates than the RALP group but similar rates to the ORP group. LRP and RALP showed significantly lower blood loss and transfusions, and a shorter length of hospital stay than the ORP group. Total perioperative complication rates were higher for ORP and LRP than for RALP. Total intraoperative complication rates were low for all modalities but lowest for RALP. Rates for readmission, reoperation, nerve, ureteral, and rectal injury, deep vein thrombosis, pneumonia, hematoma, lymphocele, anastomotic leak, fistula, and wound infection showed significant differences between groups, generally favoring RALP. The lack of randomized controlled trials, use of margin status as an indicator of oncologic control, and inability to perform cost comparisons are limitations of this study. Conclusions This meta-analysis demonstrates that RALP is at least equivalent to ORP or LRP in terms of margin rates and suggests that RALP provides certain advantages, especially regarding decreased adverse events.
Over the years, several techniques for performing robot-assisted prostatectomy have been implemented in an effort to achieve optimal oncological and functional outcomes.
To provide an evidence-based ...description and video-based illustration of currently available dissection techniques for robotic prostatectomy.
A literature search was performed to retrieve articles describing different surgical approaches and techniques for robot-assisted radical prostatectomy (RARP) and to analyze data supporting their use. Video material was provided by experts in the field to illustrate these approaches and techniques.
Multiple surgical approaches are available: extraperitoneal, transvesical, transperitoneal posterior, transperitoneal anterior, Retzius sparing, and transperineal. Surgical techniques for prostatic dissection sensu strictu are the following: omission of the endopelvic fascia dissection, bladder neck preservation, incremental nerve sparing by means of an antegrade or retrograde approach, and preservation of the puboprostatic ligaments and dorsal venous complex. Recently, techniques for total or partial prostatectomy have been described.
Different surgical approaches and techniques for robotic prostatectomy have been analyzed.
Two randomized controlled trials evaluating the extraperitoneal versus the transperitoneal approach have demonstrated similar results. Level I evidence on the Retzius-sparing approach demonstrated earlier return to continence than the traditional anterior approach. The question whether Retzius-sparing RARP is associated with a higher rate of positive surgical margins is still open due to the intrinsic bias in terms of surgical expertise in the available comparative studies. This technique also offers an advantage in patients who have received kidney transplantation. Retrospective evidence suggests that the more the anatomical dissection (eg., more periprostatic tissue is preserved), the better the functional outcome in terms of continence. Yet, two randomized controlled trials evaluating the different techniques of dissection have so far been produced. Partial prostatectomies should not be offered outside clinical trials.
Several techniques and approaches are available for prostate dissection during RARP. While the Retzius-sparing approach seems to provide earlier return to continence than the traditional anterior transperitoneal approach, no technique has been proved to be superior to other(s) in terms of long-term outcomes in randomized studies.
We have summarized available approaches for the surgical treatment of prostate cancer. Specifically, we described the different techniques that can be adopted for the surgical removal of the prostate using robotic technology.
Update on robotic cystectomy Grauer, Ralph; Wiklund, N. Peter
Current opinion in urology,
11/2021, Letnik:
31, Številka:
6
Journal Article
Purpose of review
This article aims to discuss recently published (2019–2021) studies on robot-assisted radical cystectomy (RARC) with attention to evidence comparing intracorporeal (ICUD) and ...extracorporeal urinary diversion (ECUD) in terms of intraoperative and perioperative metrics.
Recent findings
RARC produces equivalent oncological outcomes compared to open radical cystectomy (ORC). The benefits of RARC are most pronounced perioperatively. ICUD has been increasingly used at centers of excellence as it reduces intestinal exposure, which may incrementally minimize morbidity compared to ECUD or ORC. As the learning curve for ICUD diversion has flattened, retrospective analyses have emerged that suggest this technique may hold benefit over both ORC and RARC with ECUD, though current data is conflicting, and a randomized controlled study is forthcoming.
Summary
ORC is the current ‘gold standard’ management for muscle-invasive bladder cancer. Based on the premise of the minimization of perioperative morbidity, the development of RARC, most recently with ICUD, seeks to improve patient outcomes. Despite a protracted learning curve, many expert bladder cancer centers have adopted an intracorporeal approach. As more centers adopt, refine, and climb the learning curve for ICUD, a clearer insight of its effect on morbidity will be revealed—informing further adoption of the technique.