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IntroductionFocal therapy (FT) for localized prostate cancer (PCa) is a promising treatment strategy. Although, according to guidelines, it should be regarded as an experimental option, its introduction into clinical practice has occurred at an accelerated speed. It is, thus, crucial for Urologists to understand FT limitations and potential drawbacks that may derive from its use.MethodsWe performed a literature search of peer-reviewed English language articles using Pubmed and the words “focal therapy” AND “prostate cancer” to identify relevant articles. Web search was complemented by manual search.ResultsFrom a biological perspective, in contrast with the index lesion theory, which still needs to be better supported, PCa is a multifocal and multiclonal entity. Also, the effects of FT on PCa microenvironment are unclear. From a clinical perspective, patient selection is still not precisely defined. Even when all variables potentially decreasing mpMRI and biopsy accuracy are optimized, up to one out of two men may be incorrectly selected for FT, leaving a significant proportion of clinically significant PCa (csPCa) untreated. Underestimation of PCa volume and variant histologies are other additional mpMRI potential limitations. No RCTs have been performed against the standard of care to support FT. There is absence of long-term results and FT series reaching medium-term follow-up have non-optimal oncological control with significant re-treatment needs. When PCa recurs/persists after FT, little is known about the appropriate management strategies and their outcomes. Finally, the optimal follow-up scheme post-FT remains unclear.ConclusionsSeveral arguments are present against the use of FT for localized PCa. Studies are needed to overcome current limitations and support FT before it can be included as part of the standard management of prostate cancer.

BackgroundMotorized articulating laparoscopic instruments (ALI) offer more degrees of freedom than conventional laparoscopic instruments (CLI). However, a difficult learning curve and complex instrument handling are still a problem of ALI. We compared the performance of new prototypes of motorized ALI with CLI in a series of standardized laparoscopic tasks performed by laparoscopic novices. Further, usability of the new ALI was assessed.MethodsA randomized cross-over study with 50 laparoscopic novices who either started with CLI and then changed to ALI (CA) or vice versa (AC) was conducted. All participants performed the European training in basic laparoscopic urological skills (E-BLUS) with each instrument in given order. Time and errors were measured for each exercise. Instrument usability was assessed.ResultsOverall, using CLI was significantly faster (CLI 4:27 min vs. ALI 4:50 min; p-value 0.005) and associated with fewer exercise failures in needle guidance (CLI 0 vs. ALI 12; p-value 0.0005) than ALI. Median amount of errors was similar for both instruments. Instrument sequence did not matter, as CA and AC showed comparable completion times. Regarding the learning effect, participants were significantly faster in the second attempt of exercises than in the first. In the needle guidance task, participants using CLI last demonstrated a significant speed improvement, whereas ALI were significantly slower in the second run. Regarding usability, CLI were preferred over ALI due to lighter weight and easier handling. Nevertheless, participants valued ALI’s additional degrees of freedom.ConclusionUsing new motorized ALI in the E-BLUS examination by laparoscopic novices led to a worse performance compared to CLI. An explanation could be that participants felt overwhelmed by ALI and that ALI have an own distinct learning curve. As participants valued ALI’s additional degrees of freedom, however, a future application of ALI could be for training purposes, ideally in combination with CLI.

ObjectiveAge is known to have an impact on outcomes after radical prostatectomy (RP). However, age differences can be investigated from a cross-sectional as well as from a longitudinal perspective. This study combines both perspectives.Materials and methodsLAP-01 is the first multicenter randomized patient blinded trial comparing outcomes after robotic-assisted and laparoscopic RP. This study stratified the entire population that received nerve-sparing surgery and was potent at baseline by the following ages: ≤ 60 years, 61–65 years, and > 65 years. Potency was assessed using the IIEF-5. The EORTC QLQ-C30 was used for global health perception and the EORTC QLQ-PR25 for urinary symptoms. Continence was assessed by the number of pads used. Longitudinal change was assessed using either validated anchor-based criteria or the 1 or 0.5-standard-deviation criterion. Worsening of continence was measured by increasing numbers of pads.Results310 patients were included into this study. Older patients had a significantly higher risk for worsening of continence at 3 and 6 months (OR 2.21, 95% CI [1.22, 4.02], p = 0.009 and OR 2.00, 95% CI [1.16, 3.46], p = 0.013, respectively); at 12 months, the odds of worsening did not differ significantly between age groups. Potency scores were better in younger patients from a cross-sectional perspective, but longitudinal change did not differ between the age groups. In contrast, global health perception was better in older patients from a cross-sectional perspective and longitudinal decreases were significantly more common among the youngest patients, at 12 months (36.9% vs. 24.4%, p = 0.038).ConclusionFrom a cross-sectional perspective, function scores were better in younger patients, but from a longitudinal perspective, age differences were found in continence only. In contrast, global health scores were better in older patients from a cross-sectional and longitudinal perspective.Trial registrationThe LAP-01 trial was registered with the U.S. National Library of Medicine clinical trial registry (clinicaltrials.gov), NCT number: NCT03682146, and with the German Clinical Trial registry (Deutsches Register Klinischer Studien), DRKS ID number: DRKS00007138.

BackgroundWith growing interest in focal therapy (FT) of prostate cancer (PCa) there is an increasing armamentarium of treatment modalities including high-intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE), vascular targeted photodynamic therapy (VTP), focal brachytherapy (FBT) and stereotactic ablative radiotherapy (SABR). Currently there are no clear recommendations as to which of these technologies are appropriate for individual patient characteristics. Our intention was to review the literature for special aspects of the different technologies that might be of advantage depending on individual patient and tumour characteristics.MethodsThe current literature on FT was screened for the following factors: morbidity, repeatability, tumour risk category, tumour location, tumour size and prostate volume and anatomical issues. The ESUT expert panel arrived at consensus regarding a position statement on a structured pathway for available FT technologies based on a combination of the literature and expert opinion.ResultsSide effects were low across different studies and FT modalities with urinary continence rates of 90–100% and erectile dysfunction between 5 and 52%. Short to medium cancer control based on post-treatment biopsies were variable between ablative modalities. Expert consensus suggested that posterior lesions are better amenable to FT using HIFU. Cryotherapy provides best possible outcomes for anterior tumours. Apical lesions, when treated with FBT, may yield the least urethral morbidity.ConclusionsFurther prospective trials are required to assess medium to long term disease control of different ablative modalities for FT. Amongst different available FT modalities our ESUT expert consensus suggests that some may be better for diffe`rent tumour locations. Tumour risk, tumour size, tumour location, and prostate volume are all important factors to consider and might aid in designing future FT trials.

Intratumoural heterogeneity (ITH) is a major cause of cancer-associated lethality. Extensive genomic ITH has previously been reported in clear cell renal cell carcinoma (ccRCC). Here we address the question whether ITH increases with malignant progression and can hence be exploited as a prognostic marker. Unexpectedly, precision quantitative image analysis reveals that the degree of functional ITH is virtually identical between primary ccRCCs of the lowest stage and advanced, metastatic tumours. Functional ITH was found to show a stage-independent topological pattern with peak proliferative and signalling activities almost exclusively in the tumour periphery. Exome sequencing of matching peripheral and central primary tumour specimens reveals various region-specific mutations. However, these mutations cannot directly explain the zonal pattern suggesting a role of microenvironmental factors in shaping functional ITH. In conclusion, our results indicate that ITH is an early and general characteristic of malignant growth rather than a consequence of malignant progression. It has been increasingly recognised that tumours are not made up of a homogeneous population of cells. Here, the authors show heterogeneous expression of five protein markers in renal cell cancer and demonstrate that the progression of the tumour does not influence the degree of heterogeneity in the tumour.

PurposeTo analyze urinary continence outcome following robot-assisted radical prostatectomy (RARP) for aggressive prostate cancer in men aged ≥ 70 and < 70 years.MethodsRetrospective analyses of prospectively collected long-term data from a monocentric cohort of 350 men with D’Amico high-risk prostate cancer undergone robot-assisted radical prostatectomy at a single institution between 2005 and 2016. The association between time since operation and zero-pad urinary continence recovery was comparatively analyzed by separate pre-operative and post-operative Cox proportional-hazard regression models.ResultsMedian age in the age group ≥ 70 years was 73 years compared with 62 years in the < 70 year age group. Distribution of men receiving adjuvant and salvage radiotherapy/hormonal therapy was similar in both age groups. Urinary continence recovery rate at 12, 24, and 36 months after surgery of men aged ≥ 70 years was 66, 79 and 83%, respectively, and statistically similar to that of men < 70 years: 71, 81, and 85% (log-rank test p = 0.24). Multivariable analyses demonstrated no significant difference in return to continence between the two age groups (p = 0.28 and p = 0.17). In addition, clinical stage and type of nerve sparing (unilateral, bilateral or non-nerve sparing) were found to be independently predictive of pad-free continence recovery.ConclusionsRegardless of age, return to continence in men with aggressive prostate cancer undergoing RARP continues to improve way beyond the first 12 months after surgery. Considering the dire effects of post-operative radiotherapy on continence in this aggressive cancer cohort, advanced age alone should not discourage recommending multimodal therapy involving RARP.

A venous tumor thrombus (VTT) is a potentially lethal complication of renal cell carcinoma (RCC) but virtually nothing is known about the underlying natural history. Based on our observation that venous thrombi contain significant numbers of viable tumor cells, we applied multiregion whole exome sequencing to a total of 37 primary tumor and VTT samples including normal tissue specimens from five consecutive patients. Our findings demonstrate mutational heterogeneity between primary tumor and VTT with 106 of 483 genes (22%) harboring functional SNVs and/or indels altered in either primary tumor or thrombus. Reconstruction of the clonal phylogeny showed clustering of tumor samples and VTT samples, respectively, in the majority of tumors. However, no new subclones were detected suggesting that pre-existing subclones of the primary tumor drive VTT formation. Importantly, we found several lines of evidence for “BRCAness” in a subset of tumors. These included mutations in genes that confer “BRCAness”, a mutational signature and an increase of small indels. Re-analysis of SNV calls from the TCGA KIRC-US cohort confirmed a high frequency of the “BRCAness” mutational signature AC3 in clear cell RCC. Our findings warrant further pre-clinical experiments and may lead to novel personalized therapies for RCC patients.

Purpose To analyze postoperative complications after laparoscopic radical cystectomy (LRC) and evaluate its risk factors in a large prospective cohort built by the ESUT across European centers involved in minimally invasive urology in the last decade. Methods Patients were prospectively enrolled, and data were retrospectively analyzed. Only oncologic cases were included. There were no formal contraindications for LRC: Also patients with locally advanced tumors (pT4a), serious comorbidities, and previous major abdominal surgery were enrolled. All procedures were performed via a standard laparoscopic approach, with no robotic assistance. Early and late postoperative complications were graded according to the modified Clavien–Dindo classification. Multivariate logistic regression was performed to explore possible risk factors for developing complications. Results A total of 548 patients were available for final analysis, of which 258 (47 %) experienced early complications during the first 90 days after LRC. Infectious, gastrointestinal, and genitourinary were, respectively, the most frequent systems involved. Postoperative ileus occurred in 51/548 (9.3 %) patients. A total of 65/548 (12 %) patients underwent surgical re-operation, and 10/548 (2 %) patients died in the early postoperative period. Increased BMI ( p  = 0.024), blood loss ( p  = 0.021), and neoadjuvant treatment ( p  = 0.016) were significantly associated with a greater overall risk of experiencing complications on multivariate logistic regression. Long-term complications were documented in 64/548 (12 %), and involved mainly stenosis of the uretero-ileal anastomosis or incisional hernias. Conclusions In this multicenter, prospective, large database, LRC appears to be a safe but morbid procedure. Standardized complication reporting should be encouraged to evaluate objectively a surgical procedure and permit comparison across studies.

Although digital and data-based technologies are widespread in various industries in the context of Industry 4.0, the use of smart connected devices in health care is still in its infancy. Innovative solutions for the medical environment are affected by difficult access to medical device data and high barriers to market entry because of proprietary systems. In the proof-of-concept project OP 4.1, we show the business viability of connecting and augmenting medical devices and data through software add-ons by giving companies a technical and commercial platform for the development, implementation, distribution, and billing of innovative software solutions. The creation of a central platform prototype requires the collaboration of several independent market contenders, including medical users, software developers, medical device manufacturers, and platform providers. A dedicated consortium of clinical and scientific partners as well as industry partners was set up. We demonstrate the successful development of the prototype of a user-centric, open, and extensible platform for the intelligent support of processes starting with the operating room. By connecting heterogeneous data sources and medical devices from different manufacturers and making them accessible for software developers and medical users, the cloud-based platform OP 4.1 enables the augmentation of medical devices and procedures through software-based solutions. The platform also allows for the demand-oriented billing of apps and medical devices, thus permitting software-based solutions to fast-track their economic development and become commercially successful. The technology and business platform OP 4.1 creates a multisided market for the successful development, implementation, distribution, and billing of new software solutions in the operating room and in the health care sector in general. Consequently, software-based medical innovation can be translated into clinical routine quickly, efficiently, and cost-effectively, optimizing the treatment of patients through smartly assisted procedures.

Key Points Robot-assisted surgery has revolutionized laparoscopy, particularly enabling surgeons with no laparoscopic training to learn and perform reconstructive procedures with a shortened learning curve Laparoscopic surgery will benefit from new developments, such as 4K ultrahigh-definition and 3D high-definition video technology, flexible instruments, suturing devices, and sealing devices using bipolar and ultrasound technology Sophisticated camera holders and ergonomic platforms, enabling the surgeon to perform the procedure in a sitting position or with arm and chest support, will further benefit laparoscopic surgery The use of specific platforms for single-site surgery might increase the application of laparoendoscopic single-site surgery for urological indications Laparoscopy remains an important surgical technique, particularly for ablative procedures Distribution of robot-assisted surgery is limited by high purchase and maintenance costs for the only existing robotic system, but new robots are expected soon Laparoscopic techniques are subject to continuous change and benefit from new developments. Robot-assisted surgery has substantially revolutionized laparoscopy, increasing its distribution; however, it is associated with considerable costs. In this Review, Rassweiler and Teber discuss technical improvements, developing technologies and speculate on the future of minimally invasive surgery and laparoscopy in urology. In the past 10 years, laparoscopy has been challenged by robotic surgery; nevertheless, laparoscopic techniques are subject to continuous change. Ultrahigh definition is the next development in video technology, it delivers fourfold more detail than full high definition resulting in improved fine detail, increased texture, and an almost photographic emulsion of smoothness of the image. New 4K ultrahigh-definition technology might remove the current need for the use of polarized glasses. New devices for laparoscopy include advanced sealing devices, instruments with six degrees of freedom, ergonomic platforms with armrests and a chest support, and camera holders. A manually manipulated robot-like device is still at the experimental stage. Robot-assisted surgery has substantially revolutionized laparoscopy, increasing its distribution; however, robot-assisted surgery is associated with considerable costs. All technical improvements of laparoscopic surgery are extremely valuable to further simplify the use of classical laparoscopy.