Publications by authors named "Giancarlo Marra"

134 Publications

An Algorithm to Personalize Nerve Sparing in Men with Unilateral High-Risk Prostate Cancer.

J Urol 2021 Sep 22:101097JU0000000000002205. Epub 2021 Sep 22.

Department of Urology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Purpose: Current guidelines do not provide strong recommendations on the preservation of the neurovascular bundles during RP in case of HR PCa and/or suspicious EPE. We aimed to evaluate when, in case of unilateral HR disease, contralateral NS should be considered or not.

Methods: Within a multi-institutional dataset we selected patients with unilateral HR PCa defined as: unilateral EPE and/or SVI on mpMRI or unilateral ISUP 4-5 or PSA ≥20 ng/ml. To evaluate when to perform NS based on the risk of contralateral EPE, we relied on CHAID, a recursive machine learning partitioning algorithm developed to identify risk groups, which was fit to predict the presence of EPE on final pathology, contralaterally to the prostate lobe with HR disease.

Results: 705 patients were identified. Contralateral EPE was documented in 87 (12%) patients. The CHAID identified three groups: i) absence of SVI on mpMRI and index lesion's diameter ≤15 mm; ii) index lesion's diameter ≤15 mm and contralateral ISUP 2-3 or index lesion's diameter >15 mm and negative contralateral biopsy or ISUP 1 iii) SVI on mpMRI or index lesion's diameter >15 mm and contralateral biopsy ISUP 2-3. We named those groups as low- intermediate- and high-risk for contralateral EPE. The rate of EPE and PSMs across the groups were: 4.8%, 14%, 26% and 5.6%, 13%, 18%, respectively.

Conclusions: Our study challenges current guidelines by proving that wide bilateral excision in men with unilateral HR disease is not justified. Pending external validation, we propose performing NS and incremental NS in case of contralateral low- and intermediate EPE risk, respectively.
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http://dx.doi.org/10.1097/JU.0000000000002205DOI Listing
September 2021

Survival Outcomes After Immediate Radical Cystectomy Versus Conservative Management with Bacillus Calmette-Guérin Among T1 High-grade Micropapillary Bladder Cancer Patients: Results from a Multicentre Collaboration.

Eur Urol Focus 2021 Aug 18. Epub 2021 Aug 18.

Department of Urology, Spedali Civili di Brescia, Brescia, Italy.

Background: Literature lacks clear evidence regarding the optimal treatment for non-muscle-invasive micropapillary bladder cancer (MPBC) due to its rarity and the presence of only small sample size and single-centre studies.

Objective: To assess cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and conservative management among T1 high-grade (HG) MPBC.

Design, Setting, And Participants: We retrospectively analysed a multicentre dataset including 119 T1 HG MPBC patients treated between 2005 and 2019 at 15 tertiary referral centres. The median follow-up time was 35 mo (interquartile range: 19-64).

Intervention: Patients underwent immediate RC versus conservative management with bacillus Calmette-Guérin.

Outcomes Measurements And Statistical Analysis: Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Multivariable Cox analyses were performed to assess independent predictors of disease recurrence and disease progression after conservative management; covariates consisted of pure MPBC, concomitant lymphovascular invasion (LVI), and carcinoma in situ at initial diagnosis.

Results And Limitations: Immediate RC and conservative management were performed in 27% and 73% of patients, respectively. CSM and OM did not differ significantly among patient treated with immediate RC versus conservative management (Pepe-Mori test p = 0.5 and log-rank test p = 0.9, respectively). Overall, 66.7% and 34.5% of patients experienced disease recurrence and disease progression after conservative management, respectively. At multivariable Cox analyses, concomitant LVI was an independent predictor of disease recurrence (p = 0.01) and progression (p = 0.03), while pure MPBC was independently associated with disease progression (p = 0.03). The absence of a centralised re-review and the retrospective design represent the main limitations of our study.

Conclusions: Conservative management could achieve satisfactory results among T1 HG MPBC patients with neither pure MPBC nor LVI at initial diagnosis.

Patient Summary: Bacillus Calmette-Guérin seems to be an effective therapy for T1 micropapillary bladder cancer patients with neither pure micropapillary disease nor lymphovascular invasion at initial diagnosis.
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http://dx.doi.org/10.1016/j.euf.2021.07.015DOI Listing
August 2021

Risk Stratification of Patients Candidate to Radical Prostatectomy Based on Clinical and Multiparametric Magnetic Resonance Imaging Parameters: Development and External Validation of Novel Risk Groups.

Eur Urol 2021 Aug 13. Epub 2021 Aug 13.

Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.

Background: Despite the key importance of magnetic resonance imaging (MRI) parameters, risk classification systems for biochemical recurrence (BCR) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) are still based on clinical variables alone.

Objective: We aimed at developing and validating a novel classification integrating clinical and radiological parameters.

Design, Setting, And Participants: A retrospective multicenter cohort study was conducted between 2014 and 2020 across seven academic international referral centers. A total of 2565 patients treated with RP for PCa were identified.

Outcome Measurements And Statistical Analysis: Early BCR was defined as two prostate-specific antigen (PSA) values of ≥0.2 ng/ml within 3 yr after RP. Kaplan-Meier and Cox regressions tested time and predictors of BCR. Development and validation cohorts were generated from the overall patient sample. A model predicting early BCR based on Cox-derived coefficients represented the basis for a nomogram that was validated externally. Predictors consisted of PSA, biopsy grade group, MRI stage, and the maximum diameter of lesion at MRI. Novel risk categories were then identified. The Harrel's concordance index (c-index) compared the accuracy of our risk stratification with the European Association of Urology (EAU), Cancer of the Prostate Risk Assessment (CAPRA), and International Staging Collaboration for Cancer of the Prostate (STAR-CAP) risk groups in predicting early BCR.

Results And Limitations: Overall, 200 (8%), 1834 (71%), and 531 (21%) had low-, intermediate-, and high-risk disease according to the EAU risk groups. The 3-yr overall BCR-free survival rate was 84%. No differences were observed in the 3-yr BCR-free survival between EAU low- and intermediate-risk groups (88% vs 87%; p = 0.1). The novel nomogram depicted optimal discrimination at external validation (c-index 78%). Four new risk categories were identified based on the predictors included in the Cox-based nomogram. This new risk classification had higher accuracy in predicting early BCR (c-index 70%) than the EAU, CAPRA, and STAR-CAP risk classifications (c-index 64%, 63%, and 67%, respectively).

Conclusions: We developed and externally validated four novel categories based on clinical and radiological parameters to predict early BCR. This novel classification exhibited higher accuracy than the available tools.

Patient Summary: Our novel and straightforward risk classification outperformed currently available preoperative risk tools and should, therefore, assist physicians in preoperative counseling of men candidate to radical treatment for prostate cancer.
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http://dx.doi.org/10.1016/j.eururo.2021.07.027DOI Listing
August 2021

Editorial Comment.

Authors:
Giancarlo Marra

J Urol 2021 11 12;206(5):1191. Epub 2021 Aug 12.

Department of Surgical Sciences, Città della Salute e della Scienza and University of Turin, Turin, Italy.

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http://dx.doi.org/10.1097/JU.0000000000001939.01DOI Listing
November 2021

Disentangling tumorigenesis-associated DNA methylation changes in colorectal tissues from those associated with ageing.

Epigenetics 2021 Aug 9:1-18. Epub 2021 Aug 9.

Institute of Molecular Cancer Research, University of Zurich, Switzerland.

Physiological ageing and tumorigenesis are both associated with epigenomic alterations in human tissue cells, the most extensively investigated of which entails de novo cytosine methylation (i.e., hypermethylation) within the CpG dinucleotides of CpG islands. Genomic regions that become hypermethylated during tumorigenesis are generally believed to overlap regions that acquire methylation in normal tissues as an effect of ageing. To define the extension of this overlap, we analysed the DNA methylomes of 48 large-bowel tissue samples taken from women of different ages during screening colonoscopy: 18 paired samples of normal and lesional tissues from donors harbouring a precancerous lesion and 12 samples of normal mucosa from tumour-free donors. Each sample was subjected to targeted, genome-wide bisulphite sequencing of ~2.5% of the genome, including all CpG islands. In terms of both its magnitude and extension along the chromatin, tumour-associated DNA hypermethylation in these regions was much more conspicuous than that observed in the normal mucosal samples from older (vs. younger) tumour-free donors. 83% of the ageing-associated hypermethylated regions (n = 2501) coincided with hypermethylated regions observed in tumour samples. However, 86% of the regions displaying hypermethylation in precancerous lesions (n = 16,772) showed no methylation changes in the ageing normal mucosa. The tumour-specificity of this latter hypermethylation was validated using published sets of data on DNA methylation in normal and neoplastic colon tissues. This extensive set of genomic regions displaying tumour-specific hypermethylation represents a rich vein of putative biomarkers for the early, non-invasive detection of colorectal tumours in women of all ages.
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http://dx.doi.org/10.1080/15592294.2021.1952375DOI Listing
August 2021

Focal Therapy for Prostate Cancer: Complications and Their Treatment.

Front Surg 2021 12;8:696242. Epub 2021 Jul 12.

Department of Urology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Focal therapy is a modern alternative to selectively treat a specific part of the prostate harboring clinically significant disease while preserving the rest of the gland. The aim of this therapeutic approach is to retain the oncological benefit of active treatment and to minimize the side-effects of common radical treatments. The oncological effectiveness of focal therapy is yet to be proven in long-term robust trials. In contrast, the toxicity profile is well-established in randomized controlled trials and multiple robust prospective cohort studies. This narrative review summarizes the relevant evidence on complications and their management after focal therapy. When compared to whole gland treatments, focal therapy provides a substantial benefit in terms of adverse events reduction and preservation of genito-urinary function. The most common complications occur in the peri-operative period. Urinary tract infection and acute urinary retention can occur in up to 17% of patients, while dysuria and haematuria are more common. Urinary incontinence following focal therapy is very rare (0-5%), and the vast majority of patients recover in few weeks. Erectile dysfunction can occur after focal therapy in 0-46%: the baseline function and the ablation template are the most important factors predicting post-operative erectile dysfunction. Focal therapy in the salvage setting after external beam radiotherapy has a significantly higher rate of complications. Up to one man in 10 will present a severe complication.
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http://dx.doi.org/10.3389/fsurg.2021.696242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311122PMC
July 2021

Radiation Therapy After Radical Prostatectomy: What Has Changed Over Time?

Front Surg 2021 9;8:691473. Epub 2021 Jul 9.

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

The role and timing of radiotherapy (RT) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) remains controversial. While recent trials support the oncological safety of early salvage RT (SRT) compared to adjuvant RT (ART) in selected patients, previous randomized studies demonstrated that ART might improve recurrence-free survival in patients at high risk for local recurrence based on adverse pathology. Although ART might improve survival, this approach is characterized by a risk of overtreatment in up to 40% of cases. SRT is defined as the administration of RT to the prostatic bed and to the surrounding tissues in the patient with PSA recurrence after surgery but no evidence of distant metastatic disease. The delivery of salvage therapies exclusively in men who experience biochemical recurrence (BCR) has the potential advantage of reducing the risk of side effects without theoretically compromising outcomes. However, how to select patients at risk of progression who are more likely to benefit from a more aggressive treatment after RP, the exact timing of RT after RP, and the use of hormone therapy and its duration at the time of RT are still open issues. Moreover, what the role of novel imaging techniques and genomic classifiers are in identifying the most optimal post-operative management of PCa patients treated with RP is yet to be clarified. This narrative review summarizes most relevant published data to guide a multidisciplinary team in selecting appropriate candidates for post-prostatectomy radiation therapy.
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http://dx.doi.org/10.3389/fsurg.2021.691473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298897PMC
July 2021

Radical Prostatectomy: Sequelae in the Course of Time.

Front Surg 2021 28;8:684088. Epub 2021 May 28.

Division of Oncology/Unit of Urology, Urological Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy.

Radical prostatectomy (RP) is a frequent treatment for men suffering from localized prostate cancer (PCa). Whilst offering a high chance for cure, it does not come without a significant impact on health-related quality of life. Herein we review the common adverse effects RP may have over the course of time. A collaborative narrative review was performed with the identification of the principal studies on the topic. The search was executed by a relevant term search on PubMed from 2010 to February 2021. Rates of major complications in patients undergoing RP are generally low. The main adverse effects are erectile dysfunction varying from 11 to 87% and urinary incontinence varying from 0 to 87% with a peak in functional decline shortly after surgery, and dependent on definitions. Different less frequent side effects also need to be taken into account. The highest rate of recovery is seen within the first year after RP, but even long-term improvements are possible. Nevertheless, for some men these adverse effects are long lasting and different, less frequent side effects also need to be taken into account. Despite many technical advances over the last two decades no surgical approach can be clearly favored when looking at long-term outcome, as surgical volume and experience as well as individual patient characteristics are still the most influential variables. The frequency of erectile function and urinary continence side effects after RP, and the trajectory of recovery, need to be taken into account when counseling patients about their treatment options for prostate cancer.
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http://dx.doi.org/10.3389/fsurg.2021.684088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193923PMC
May 2021

The role of lymph node dissection in salvage radical prostatectomy for patients with radiation recurrent prostate cancer.

Prostate 2021 Aug 31;81(11):765-771. Epub 2021 May 31.

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

Purpose: To examine the effect of lymph node dissection on the outcomes of patients who underwent salvage radical prostatectomy (SRP).

Material And Methods: We retrospectively reviewed data from radiation-recurrent patients with prostate cancer (PCa) who underwent SRP from 2000-2016. None of the patients had clinical lymph node involvement before SRP. The effect of the number of removed lymph nodes (RLNs) and the number of positive lymph nodes (PLNs) on biochemical recurrence (BCR)-free survival, metastases free survival, and overall survival (OS) was tested in multivariable Cox regression analyses.

Results: About 334 patients underwent SRP and pelvic lymph node dissection (PLND). Lymph node involvement was associated with increased risk of BCR (p < .001), metastasis (p < .001), and overall mortality (p = .006). In a multivariable Cox regression analysis, an increased number of RLNs significantly lowered the risk of BCR (hazard ratio [HR] 0.96, p = .01). In patients with positive lymph nodes, a higher number of RLNs and a lower number of PLNs were associated with improved freedom from BCR (HR 0.89, p = .001 and HR 1.34, p = .008, respectively). At a median follow-up of 23.9 months (interquartile range, 4.7-37.7), neither the number of RLNs nor the number of PLNs were associated with OS (p = .69 and p = .34, respectively).

Conclusion: Pathologic lymph node involvement increased the risk of BCR, metastasis and overall mortality in radiation-recurrent PCa patients undergoing SRP. The risk of BCR decreased steadily with a higher number of RLNs during SRP. Further research is needed to support this conclusion and develop a precise therapeutic adjuvant strategy based on the number of RLNs and PLNs.
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http://dx.doi.org/10.1002/pros.24173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361975PMC
August 2021

Available evidence on HIFU for focal treatment of prostate cancer: a systematic review.

Int Braz J Urol 2021 Apr 20;47. Epub 2021 Apr 20.

Department of Urology, Institut Mutualiste Montsouris, Paris, France.

Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa.

Material And Methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included.

Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade.

Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2021.0091DOI Listing
April 2021

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study.

BJU Int 2021 Oct 8;128(4):440-450. Epub 2021 Sep 8.

Great Western Hospitals NHS Foundation Trust, Swindon, UK.

Objective: To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation.

Patients And Methods: This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries.

Results: Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3-34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1-30.2), UTUC (n = 128) 1.14% (95% CI 0.77-1.52), renal cancer (n = 107) 1.05% (95% CI 0.80-1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32-2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03-1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90-4.15; P < 0.001), male sex 1.30 (95% CI 1.14-1.50; P < 0.001), and smoking 2.70 (95% CI 2.30-3.18; P < 0.001).

Conclusions: A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer.
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http://dx.doi.org/10.1111/bju.15483DOI Listing
October 2021

Editorial Comment.

Authors:
Giancarlo Marra

J Urol 2021 08 7;206(2):317. Epub 2021 May 7.

Department of Surgical Sciences, Città della Salute e della Scienza and University of Turin, Turin, Italy.

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http://dx.doi.org/10.1097/JU.0000000000001776.01DOI Listing
August 2021

Long-term Outcomes of Focal Cryotherapy for Low- to Intermediate-risk Prostate Cancer: Results and Matched Pair Analysis with Active Surveillance.

Eur Urol Focus 2021 Apr 26. Epub 2021 Apr 26.

Department of Urology, Institut Mutualiste Montsouris and Université Paris Descartes, Paris, France.

Background: To date, only one trial compared focal therapy and active surveillance (AS) for low-risk prostate cancer (PCa). In addition, long-term outcomes of focal cryotherapy (FC) are lacking.

Objective: Our aim was to evaluate long-term outcomes of FC and compare them with AS.

Design, Setting, And Participants: We included two prospective series of 121 (FC) and 459 (AS) consecutive patients (2008-2018) for low- to intermediate-risk PCa.

Outcome Measurements And Statistical Analysis: Study outcomes were radical therapy-free or androgen deprivation therapy (ADT)-free, any treatment-free, metastasis-free, and overall survival. A matched pair analysis was performed using seven covariates.

Results And Limitations: The median FC follow-up was 85 mo (interquartile range 58-104); 92 (76%) men had International Society of Urological Pathology (ISUP) grade 1. Among matched variables, no significant differences were present except for cT stage and year of entry (both p < 0.01). Ten-year radical therapy-free or ADT-free, any treatment-free, metastasis-free, and overall survival were 51%, 40.2%, 93.9%, and 97%, respectively for FC. No differences were noted with AS (all p > 0.05), with the exception of time to radical therapy, time to radical therapy and ADT, and time to any treatment, all being shorter for AS (all p < 0.01). Freedom from radical treatment or ADT was higher for FC (AS 10 yr 39.3%; p = 0.04). Complications were relatively rare (26.5%) and mainly of low grade (Clavien >2, n = 3); three men developed incontinence (p = 0.0814), while both International Index of Erectile Function 5 and International Prostate Symptom Score scores increased (p = 0.0287 and p = 0.0165, respectively). Limitations include absence of randomization.

Conclusions: At an early long-term follow-up, FC in the context of mainly low-risk PCa is safe and increases time to radical therapy but does not provide meaningful oncological advantages compared with AS.

Patient Summary: We compared focal cryotherapy with active surveillance mainly for low-risk prostate cancer. Focal cryotherapy, despite having fewer complications, did not yield meaningful advantages over active surveillance at 10 yr. Active surveillance should be preferred to focal cryotherapy for these patients.
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http://dx.doi.org/10.1016/j.euf.2021.04.008DOI Listing
April 2021

"Virtually Perfect" for Some but Perhaps Not for All: Launching Telemedicine in the Bronx during the COVID-19 Pandemic. Letter.

J Urol 2021 07 27;206(1):176-177. Epub 2021 Mar 27.

Department of Urology and Clinical Research Group on Predictive Onco-Urology, APHP, Sorbonne University Paris, France.

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http://dx.doi.org/10.1097/JU.0000000000001773DOI Listing
July 2021

Comparing oncological outcomes of laparoscopic vs open radical nephroureterectomy for the treatment of upper tract urothelial carcinoma: A propensity score-matched analysis.

Arab J Urol 2020 Sep 4;19(1):31-36. Epub 2020 Sep 4.

Department of Urology, Luzerner Kantonsspital, Luzern, Switzerland.

Objectives: To compare oncological outcomes of open (ORNU) and laparoscopic radical nephroureterectomy (LRNU) after controlling for preoperative patient-derived factors.

Patients And Methods: We evaluated a multi-institutional collaborative database composed of 3984 patients diagnosed with upper tract urothelial carcinoma (UTUC) treated with RNU between 2006 and 2018. To adjust for potential selection bias, propensity score matching adjusted for age, gender and American society Anesthesiology (ASA) score was performed with one ORNU patient matched to one LRNU patient. Uni- and multivariable Cox regression evaluating the risk of overall recurrence, cancer-specific mortality (CSM) and overall mortality (OM) in the overall population and after propensity matching were performed.

Results: In total, 3984 patients underwent RNU, of these 3227 (81%) patients were treated with ORNU and 757 (19%) patients with LRNU. Within a median follow-up of 62 months, 1276 recurrences, 844 CSMs and 1128 OMs were recorded. On multivariable analyses, the LRNU approach was associated with an increased risk of overall recurrence (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.03-1.54; = 0.02), but on the other hand LRNU was associated with a protective effect on CSM (HR 0.74, 95% CI 0.56-0.98; = 0.04). After propensity matching analyses adjusted for age, gender and ASA score, 757 patients treated with LRNU and 757 patients treated with ORNU were available for the analyses. On multivariable Cox regression, LRNU vs ORNU was not associated with any difference in overall recurrence ( = 0.08), CSM ( = 0.1) or OM ( = 0.9).

Conclusion: Our present data suggest that even if the type of approach to RNU was associated with different survival outcomes considering the overall population, this difference vanished when adjusted for potential confounders in propensity matching analyses. Therefore, we found that LRNU is not inferior to the ORNU approach for the treatment of UTUC.

Abbreviations: ASA: American Society of Anesthesiology; CIS: carcinoma ; CSM: cancer-specific mortality; HR: hazard ratio; IQR: interquartile range; LN: lymph node; LNI: lymph node invasion; LVI: lymphovascular invasion; OM: overall mortality; pT: pathological tumour stage; RCT: randomised controlled trial; (L)(O)RNU: (laparoscopic) (open) radical nephroureterectomy; UTUC: upper tract urothelial carcinoma.
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http://dx.doi.org/10.1080/2090598X.2020.1817720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954493PMC
September 2020

Frailty impact on postoperative complications and early mortality rates in patients undergoing radical cystectomy for bladder cancer: a systematic review.

Arab J Urol 2020 Nov 2;19(1):9-23. Epub 2020 Nov 2.

Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland.

: To assess the prevalence of frailty, a status of vulnerability to stressors leading to adverse health events, in bladder cancer patients undergoing radical cystectomy (RC), and test the impact of frailty measurements on postoperative adverse outcomes. : A systematic review of English-language articles published up to April 2020 was performed. Electronic databases were searched to quantify the frailty prevalence in RC patients and assess the predictive ability of frailty indexes on RC-related outcomes as postoperative complications, early mortality, hospitalization length (LOS), costs, discharge dispositions, readmission rate. : Eleven studies were selected. Patients' frailty was identified by Johns Hopkins indicator (JHI) in two studies, 11-item modified Frailty Index (mFI) in four, 5-item simplified FI (sFI) in three, 15-point mFI in one, Fried Frailty Criteria in one. Considering all the frailty measurements applied, 8% and 31% of patients were frail or pre-frail, respectively. Frail (43%) and pre-frail patients (35%) were more at risk of major complications compared to non-frail (27%) using sFI; with JHI the percentages of frail and non-frail were 53% versus 19%. According to JHI and mFI frailty was related to longer LOS and higher costs. JHI identified that 3% of frail patients experience in-hospital mortality versus 1.5% of non-frail. Finally, using sFI, frail (28%), and pre-frail (19%) were more likely to be discharged non-home compared to non-frail patients (8%) and had a higher risk of 30-day mortality (4% and 2% versus 1%). : Almost half of RC patients were frail or pre-frail, conditions significantly related to an increased risk of postoperative adverse events with higher rates of major complications and early mortality. The most-used frailty index was mFI, while JHI and sFI resulted the most reliable to predict early postoperative RC-related adverse outcomes and should be routinely included in clinical practice after better standardization throughout prospective comparative studies. : ACG: Adjusted Clinical Groups; ACS: American College Surgeons; AUC: area under the curve; BCa: bladder cancer; CCI: Charlson Comorbidity Index; CSHA-FI: Canadian Study of Health and Aging Frailty Index; CCS: Clavien-Dindo Classification Score; ERAS: Enhanced Recovery After Surgery; FFC: Fried Frailty Criteria; (e)(m)(s)FI: (extended) (modified) (simplified) Frailty Index; ICU: intensive care unit; IQR: interquartile range; (p)LOS: (prolonged) length of hospital stay; NSQIP: National Surgical Quality Improvement Program; OR: odds ratio; (O)PN: (open) partial nephrectomy; PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses; (O)(RA)RC: (open)(robot-assisted) radical cystectomy; (O)RN: (open) radical nephrectomy; ROC: receiver operating characteristic; RNU: radical nephroureterectomy; (R)RP: (retropubic) radical prostatectomy; RR: relative risk; THCs: total hospital charges; nephrectomy; UD: urinary diversion.
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http://dx.doi.org/10.1080/2090598X.2020.1841538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954492PMC
November 2020

Utilization of focal therapy for patients discontinuing active surveillance of prostate cancer: Recommendations of an international Delphi consensus.

Urol Oncol 2021 Mar 3. Epub 2021 Mar 3.

Division of Urology, Duke University Medical Center, Durham, NC. Electronic address:

Background: With the advancement of imaging technology, focal therapy (FT) has been gaining acceptance for the treatment of select patients with localized prostate cancer (CaP). We aim to provide details of a formal physician consensus on the utilization of FT for patients with CaP who are discontinuing active surveillance (AS).

Methods: A 3-stage Delphi consensus on CaP and FT was conducted. Consensus was defined as agreement by ≥80% of physicians. An in-person meeting was attended by 17 panelists to formulate the consensus statement.

Results: Fifty-six respondents participated in this interdisciplinary consensus study (82% urologist, 16% radiologist, 2% radiation oncology). The participants confirmed that there is a role for FT in men discontinuing AS (48% strongly agree, 39% agree). The benefit of FT over radical therapy for men coming off AS is: less invasive (91%), has a greater likelihood to preserve erectile function (91%), has a greater likelihood to preserve urinary continence (91%), has fewer side effects (86%), and has early recovery post-treatment (80%). Patients will need to undergo mpMRI of the prostate and/or a saturation biopsy to determine if they are potential candidates for FT. Our limitations include respondent's biases and that the participants of this consensus may not represent the larger medical community.

Conclusions: FT can be offered to men coming off AS between the age of 60 to 80 with grade group 2 localized cancer. This consensus from a multidisciplinary, multi-institutional, international expert panel provides a contemporary insight utilizing FT for CaP in select patients who are discontinuing AS.
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http://dx.doi.org/10.1016/j.urolonc.2021.01.027DOI Listing
March 2021

Molecular biomarkers in the context of focal therapy for prostate cancer: recommendations of a Delphi Consensus from the Focal Therapy Society.

Minerva Urol Nefrol 2021 01 13. Epub 2021 Jan 13.

Department of Urology, Città della Salute e della Scienza, University of Turin, Turin, Italy.

Background: Focal Therapy (FT) for Prostate Cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localised PCa.

Materials And Methods: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, i) the current/present role; ii) the potential/future role; iii) the recommended features for future studies. Consensus was defined using a 70% agreement threshold.

Results: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (n=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (n=3), a consensus on a partial agreement (n=1), and a consensus on uncertainty (n=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localised PCa. Research efforts in this field should be considered a priority.

Conclusions: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.
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http://dx.doi.org/10.23736/S0393-2249.20.04160-0DOI Listing
January 2021

Oncological outcomes of salvage radical prostatectomy for recurrent prostate cancer in the contemporary era: A multicenter retrospective study.

Urol Oncol 2021 05 10;39(5):296.e21-296.e29. Epub 2021 Jan 10.

Department of Urology, Mayo Clinic, Rochester, MN.

Background: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR).

Methods: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed.

Results: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up.

Conclusions: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings.
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http://dx.doi.org/10.1016/j.urolonc.2020.11.002DOI Listing
May 2021

An "expressionistic" look at serrated precancerous colorectal lesions.

Authors:
Giancarlo Marra

Diagn Pathol 2021 Jan 10;16(1). Epub 2021 Jan 10.

Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Background: Approximately 60% of colorectal cancer (CRC) precursor lesions are the genuinely-dysplastic conventional adenomas (cADNs). The others include hyperplastic polyps (HPs), sessile serrated lesions (SSL), and traditional serrated adenomas (TSAs), subtypes of a class of lesions collectively referred to as "serrated." Endoscopic and histologic differentiation between cADNs and serrated lesions, and between serrated lesion subtypes can be difficult.

Methods: We used in situ hybridization to verify the expression patterns in CRC precursors of 21 RNA molecules that appear to be promising differentiation markers on the basis of previous RNA sequencing studies.

Results: SSLs could be clearly differentiated from cADNs by the expression patterns of 9 of the 12 RNAs tested for this purpose (VSIG1, ANXA10, ACHE, SEMG1, AQP5, LINC00520, ZIC5/2, FOXD1, NKD1). Expression patterns of all 9 in HPs were similar to those in SSLs. Nine putatively HP-specific RNAs were also investigated, but none could be confirmed as such: most (e.g., HOXD13 and HOXB13), proved instead to be markers of the normal mucosa in the distal colon and rectum, where most HPs arise. TSAs displayed mixed staining patterns reflecting the presence of serrated and dysplastic glands in the same lesion.

Conclusions: Using a robust in situ hybridization protocol, we identified promising tissue-staining markers that, if validated in larger series of lesions, could facilitate more precise histologic classification of CRC precursors and, consequently, more tailored clinical follow-up of their carriers. Our findings should also fuel functional studies on the pathogenic significance of specific gene expression alterations in the initiation and evolution of CRC precursor subtypes.
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http://dx.doi.org/10.1186/s13000-020-01064-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797135PMC
January 2021

Clinical, surgical, pathological and follow-up features of kidney cancer patients with Von Hippel-Lindau syndrome: novel insights from a large consortium.

World J Urol 2021 Aug 8;39(8):2969-2975. Epub 2021 Jan 8.

Unit of Urology, University Vita-Salute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.

Purpose: To investigate the natural history and follow-up after kidney tumor treatment of Von Hippel-Lindau (VHL) patients.

Materials And Methods: A multi-institutional European consortium of patients with VHL syndrome included 96 non-metastatic patients treated at 9 urological departments (1987-2018). Descriptive and survival analyses were performed.

Results And Limitations: Median age at VHL diagnosis was 34 years (IQR 25-43). Two patients (2.1%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 60.4 vs. 68.7 vs. 30.2 vs. 15.6 vs. 15.6% of patients, respectively. 45% of patients had both CNS and pancreatic diseases alongside kidney. The median interval between VHL diagnosis and renal cancer treatment resulted 79 months (IQR 0-132), and median index tumor size leading to treatment was 35.5 mm (IQR 28-60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4 cm. With a median follow-up of 8 years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10 years, respectively. Overall mortality was 4% and 7.5% at 5 and 10 years, respectively. During the follow-up, 50% of patients did not receive a second active renal treatment. Finally, 25.3% of patients had CKD at last follow-up.

Conclusions: Mean period between VHL diagnosis and renal cancer detection is roughly three years, with significant variability. Although, most renal tumors are small low-grade, clinical progression and mortality are not negligible. Moreover, kidney function represents a key issue in VHL patients.
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http://dx.doi.org/10.1007/s00345-020-03574-5DOI Listing
August 2021

Natural history of widespread high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation: should we rebiopsy them all?

Scand J Urol 2021 Apr 7;55(2):129-134. Epub 2021 Jan 7.

Division of Urology, Città della Salute e della Scienza - Molinette Hospital, University of Turin, Turin, Italy.

Objective: To evaluate the premalignant potential of high-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP).

Methods: Patients diagnosed with monofocal HGPIN (mHGPIN), widespread HGPIN (≥4 cores, wHGPIN) and/or ASAP who underwent at least one rebiopsy during their follow-up, were enrolled. All enrollment biopsies underwent central pathologic revision. Risks for PCa were estimated using Fine and Gray method for competing risk.

Results: Pathologic revision changed the original diagnosis in 32.3% of cases. Among 336 cases enrolled, PCa was diagnosed in 164 (48.8%), and more specifically in 20 (30.3%) mHGPIN, 10 (34.5%) wHGPIN, 101 (54.0%) ASAP, and 33 (61.1%) HGPIN + ASAP (mean follow-up 124 months). Most PCa were Gleason score 6(3 + 3) (51.0%) and 7(3 + 4) (34.3%). On multivariate analysis, HGPIN + ASAP (HR 2.76,  < 0.001) and ASAP alone (HR 2.41,  < 0.001) were the only lesions significantly associated with PCa development. Of all cancers detected, 64.3% were at first rebiopsy. A rebiopsy performed within 3 months after ASAP diagnosis had a 45% chance of finding PCa. At Kaplan-Meier survival curves, median PCa-free survival was 48.1 months for HGPIN + ASAP and 64.9 months for ASAP ( 0.0005 at Log-rank test). At 1 year, 70% of HGPIN + ASAP, 73% of ASAP, 89% of wHGPIN, and 84% of mHGPIN were PCa-free.

Conclusion: The diagnosis of ASAP and HGPIN strongly relies on the expertise of dedicated uro-pathologists. Finding of ASAP is a strong risk factor for a subsequent PCa diagnosis, advising a rebiopsy, possibly within 3 months. m/wHGPIN should not be routinely rebiopsied.
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http://dx.doi.org/10.1080/21681805.2020.1866659DOI Listing
April 2021

A Systematic Review of the Emerging Role of Immune Checkpoint Inhibitors in Metastatic Castration-resistant Prostate Cancer: Will Combination Strategies Improve Efficacy?

Eur Urol Oncol 2020 Nov 23. Epub 2020 Nov 23.

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Context: The role of immune checkpoint inhibition (ICI) in the treatment of prostate cancer (PC) still remains elusive. It has been proposed that combination of ICI with other molecules increases the efficacy of immunotherapy in PC.

Objective: To systematically review the literature to assess the potential role of ICI in combination with additional therapies for the management of metastatic castration-resistant PC (mCRPC).

Evidence Acquisition: A systematic review using Medline and scientific meeting records was carried out in September 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. Ongoing trials of immunotherapy with standard mCRPC therapeutics were identified via a systematic search on ClinicalTrials.gov.

Evidence Synthesis: A total of five full-text papers, ten congress abstracts, and 15 trials on ClinicalTrials.gov were identified. Preclinical evidence suggests that combinational approaches might be considered to enhance the efficacy of ICI in PC patients. This led to the design of more than 50 immunotherapy-based clinical trials. The majority of the studies focus on ICI combinations with vaccines, androgen deprivation therapy, chemotherapy, PARP inhibition, radiotherapy, and prostate-specific membrane antigen-guided radioligand therapy. Preliminary analyses reported promising findings for the use of ICI in combination with other anticancer therapies. However, no phase 3 trial has yet reported final results, so no level 1 evidence with long-term outcomes currently supports the combination of ICI with mCRPC therapies.

Conclusions: Preclinical and clinical trials have demonstrated that combining immunotherapy with standard mCRPC treatment options has the potential to provide a synergistic effect. Nonetheless, a better understanding of the mechanism and of the optimal treatment approach is still needed.

Patient Summary: We reviewed the literature on immunotherapy in combination with standard treatments for patients with metastatic castration-resistant prostate cancer (mCRPC). Current evidence supports the hypothesis that immunotherapeutic drugs might be effective in mCRPC if combined with other treatment options. However, results of ongoing trials are still awaited before this novel treatment approach can be implemented in the daily practice.
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http://dx.doi.org/10.1016/j.euo.2020.10.010DOI Listing
November 2020

Is partial nephrectomy safe and effective in the setting of frail comorbid patients affected by renal cell carcinoma? Insights from the RECORD 2 multicentre prospective study.

Urol Oncol 2021 01 27;39(1):78.e17-78.e26. Epub 2020 Oct 27.

Department of Urology, University of Florence, Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, Florence, Italy. Electronic address:

Background: To investigate the perioperative and morbidity outcomes after partial nephrectomy (PN) in patients with short life expectancy (SLE) (≥95% 10-year expected mortality (10y-EM)), to assess the main predictors of outcomes in this population and to compare these results with those of a group at the opposite upper range with long LE (LLE, ≤5% 10y-EM) relying on a multicenter Italian prospective registry of kidney surgery (the RECORD 2 project).

Methods: Clinical data of 4,325 patients undergone kidney surgery were collected at 26 urological Italian Centers from 2013 to 2016. SLE was defined as a ≥95% 10y-EM (assessed using the age-adjusted Charlson comorbidity index [CCI]). A multivariable logistic regression for overall postoperative complications, acute kidney injury (AKI), positive surgical margins (SM) and ∆ estimated glomerular filtration rate (eGFR) ≥25% at 2 years from surgery was performed in patients with SLE including clinically relevant variables. Adjusted outcomes reported as mean (SD) of the 2 groups were generated using separate multivariable logistic regression models and compared.

Results: Overall, 559 patients with SLE were selected. Patients had an ASA score ≥3 in 58.4% of cases. A clinical T1a, T1b, and T2 stage was found in 412 (74.5%), 124 (22.4%), and 17 (3.1%) patients. The median PADUA score was 7 (6-8). Surgical and medical postoperative complication rates were registered in 14.8% and 6% cases. Postoperative AKI was reported in 27.3% cases, positive surgical margins (PSM) in 9.3% cases. In this subgroup of patients, ASA score, cerebrovascular disease, surgery in low volume centers, and open surgery were independent predictors of overall complications. ASA and PADUA scores, renal clamping, resection technique and lower eGFR at baseline were independent predictors of AKI. PADUA score, open approach and resection technique were independent predictors of PSM. Cardiovascular disease, hilar clamping, and resection technique were independent predictors of eGFR decrease >25% at 2 years from surgery. Patients with SLE were compared with those with LLE (n = 302). All analyzed parameters at baseline were significantly different among the groups with the exception of cancer laterality. After adjusting for several clinical variables, the SLE group had a significantly higher risk rate of adjusted overall postoperative complication rate compared to the LLE group (20.6% ± 0.36 vs. 9.9% ± 0.65, P < 0.0001), while the overall intraoperative complications (4.1% ±0.13 vs. 2.3% ± 0.23), overall postoperative major complications (3.8% ± 0.09 vs. 1.9% ± 0.14) adjusted AKI (24.2% ± 0.37 vs. 22.6% ± 0.92), positive surgical margins (8% ± 0.22 vs. 6.4% ± 0.49), and 2-year RF loss (13.4% ± 0.17 vs. 12.4% ± 0.74).

Conclusion: In selected patients with SLE, PN is feasible with an acceptable safety profile that is overall comparable to patients with no LE limitations. While a robotic approach and surgery performed in high volume centers could reduce the risk of complications, an off-clamp approach and a SE surgical technique may decrease the risk of postoperative AKI and of longer term eGFR decrease.
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http://dx.doi.org/10.1016/j.urolonc.2020.09.022DOI Listing
January 2021

The effectiveness of multiparametric magnetic resonance imaging in bladder cancer (Vesical Imaging-Reporting and Data System): A systematic review.

Arab J Urol 2020 Mar 1;18(2):67-71. Epub 2020 Mar 1.

Department of Urology, Luzerner Kantonsspital, Spitalstrasse, Luzern, Switzerland.

Objective: To evaluate the role of the Vesical Imaging-Reporting and Data System (VI-RADS) score in the diagnostic pathway of bladder cancer.

Methods: A systemic search of the contemporary literature was performed in December 2019 using the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE), and Web of Science databases focussing on all available articles on VI-RADS.

Results: Overall, six of 15 articles were included. All the available articles evaluated the ability of radiologists to use the VI-RADS score for discriminating non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC). Considering a cut-off VI-RADS score of >2, the sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were 78-91.9%, 85-91%.1, 69-78%, and 88-97.1%, respectively. Considering a VI-RADS score cut-off of >3, the sensitivity, specificity, PPV and NPV were 77-94.6%, 43.9-96.5%, 51.6-86%, and 63.7-93%, respectively. Good interobserver agreement was demonstrated in the evaluated studies with a κ score of 0.73-0.89. Only one study evaluated the utility of VI-RADS in determining the presence of MIBC in patients treated with transurethral resection of the bladder diagnosed with high-grade T1 before the second transurethral resection using a VI-RADS score cut-off of >2; the sensitivity, specificity, PPV and NPV were 85%, 93.6%, 74.5%, and 96.6%, respectively.

Conclusion: The VI-RADS score, using multiparametric magnetic resonance imaging, showed excellent results in discriminating MIBC from NMIBC. Preliminary results have been reported for its use in patients with high-grade T1 bladder cancer. These results need to be validated in high-quality real-world settings.

Abbreviations: DCE: dynamic contrast enhancement; DWI: diffusion-weighted imaging; (N)MIBC: (non-)muscle-invasive bladder cancer; mpMRI: multiparametric MRI; TURBT: transurethral resection of bladder tumour; (N)(P)PV: (negative) (positive) predictive value; SC: structural category; T2W: T2-weighted; VI-RADS: vesical imaging-reporting and data system.
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http://dx.doi.org/10.1080/2090598X.2020.1733818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473244PMC
March 2020

Initial Experience with Radical Prostatectomy Following Holmium Laser Enucleation of the Prostate.

Eur Urol Focus 2020 Sep 19. Epub 2020 Sep 19.

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Background: Although an increasing number of prostate cancer (PCa) patients received holmium laser enucleation of the prostate (HoLEP) previously for benign prostatic obstruction (BPO), there is still no evidence regarding the outcomes of radical prostatectomy (RP) in this setting.

Objective: To assess functional and oncological results of RP in PCa patients who received HoLEP for BPO previously in a contemporary multi-institutional cohort.

Design, Setting, And Participants: A total of 95 patients who underwent RP between 2011 and 2019 and had a history of HoLEP were identified in two institutions. Functional as well as oncological follow-up was prospectively assessed and retrospectively analyzed.

Intervention: RP following HoLEP compared with RP without previous transurethral surgery.

Outcome Measurements And Statistical Analysis: Patients with complete follow-up data were matched with individuals with no history of BPO surgery using propensity score matching. Complications were assessed using the Clavien-Dindo scale.

Results And Limitations: The median follow-up was 50.5 mo. We found no significant impact of previous HoLEP on positive surgical margin rate (14.0% [HoLEP] vs 18.8% [no HoLEP], p =  0.06) and biochemical recurrence-free survival (hazard ratio 0.74, 95% confidence interval [CI] 0.32-1.70, p =  0.4). Patients with a history of HoLEP had increased 1-yr urinary incontinence rates after RP. After adjusting for confounders, no significant impact of previous HoLEP was found (odds ratio [OR] 0.87, 95% CI 0.74-1.01; p = 0.07). Previous HoLEP did not hamper 1-yr erectile function recovery (OR 1.22, 95% CI 1.05-1.43; p =  0.01). Limitations include retrospective design and small sample size.

Conclusions: RP after previous HoLEP is surgically feasible, with low complication rates and no negative impact on biochemical recurrence-free survival. However, in a multivariable analysis, we observed significantly worse 1-yr continence rates in patients after previous HoLEP.

Patient Summary: In the current study, we assessed the oncological and functional outcomes of radical prostatectomy in patients who underwent holmium laser enucleation of the prostate (HoLEP) previously due to prostatic bladder outlet obstruction. A history of HoLEP did not hamper oncological results, 1-yr continence, and erectile function recovery.
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http://dx.doi.org/10.1016/j.euf.2020.09.003DOI Listing
September 2020

Management of Patients with Node-positive Prostate Cancer at Radical Prostatectomy and Pelvic Lymph Node Dissection: A Systematic Review.

Eur Urol Oncol 2020 10 12;3(5):565-581. Epub 2020 Sep 12.

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Context: Optimal management of prostate cancer (PCa) patients with lymph node invasion at radical prostatectomy and pelvic lymph node dissection still remains unclear.

Objective: To assess the effectiveness of postoperative treatment strategies for pathologically node-positive PCa patients. The secondary aim was to identify the most relevant prognostic factors to guide the management of pN1 patients.

Evidence Acquisition: A systematic review was performed in January 2020 using Medline, Embase, and other databases. A total of 5063 articles were screened, and 26 studies including 12 537 men were selected for data synthesis and included in the current review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations.

Evidence Synthesis: Ten-year biochemical recurrence (BCR)-free, clinical recurrence-free, cancer-specific (CSS), and overall (OS) survival rates ranged from 28% to 56%, 70% to 92%, 72% to 98%, and 60% to 87.6%, respectively. A total of seven, five, and six studies assessed the oncological outcomes of observation, adjuvant radiotherapy (aRT), or adjuvant androgen deprivation therapy (ADT), respectively. Initial observation followed by salvage therapies at the time of recurrence represents a safe option in selected patients with a low disease burden. The use of aRT with or without ADT might improve survival in men with locally advanced disease and a higher number of positive nodes. Risk stratification according to pathological Gleason score, number of positive nodes, pathological stage, and surgical margins status is the key to risk stratification and selection of the optimal postoperative therapy. Limitations of this systematic review are the retrospective design of the studies included and the lack of data on adverse events.

Conclusions: While the majority of men with pN1 disease would experience BCR after surgery, long-term disease-free survival has been reported in selected patients. Management options to improve oncological outcomes include observation versus adjuvant therapies such as aRT and/or ADT. Disease characteristics should be used to select the optimal postoperative management for pN1 PCa patients.

Patient Summary: Finding node-positive prostate cancer after a radical prostatectomy often leads to high postoperative prostate-specific antigen levels and is overall a poor prognostic factor. However, this does not necessarily translate into poor survival for all men. Management can be tailored to the severity of disease and options include observation, androgen deprivation therapy, and/or radiotherapy.
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http://dx.doi.org/10.1016/j.euo.2020.08.005DOI Listing
October 2020

Indications for and complications of pelvic lymph node dissection in prostate cancer: accuracy of available nomograms for the prediction of lymph node invasion.

BJU Int 2021 03 19;127(3):318-325. Epub 2020 Sep 19.

Division of Urology, Città della Salute e della Scienza, Molinette Hospital, University of Turin, Torino, Italy.

Objectives: To externally validate the currently available nomograms for predicting lymph node invasion (LNI) in patients with prostate cancer (PCa) and to assess the potential risk of complications of extended pelvic lymph node dissection (ePLND) when using the recommended threshold.

Methods: A total of 14 921 patients, who underwent radical prostatectomy with ePLND at eight European tertiary referral centres, were retrospectively identified. After exclusion of patients with incomplete biopsy or pathological data, 12 009 were included. Of these, 609 had undergone multiparametic magnetic resonance imaging-targeted biopsies. Among ePLND-related complications we included lymphocele, lymphoedema, haemorrhage, infection and sepsis. The performances of the Memorial Sloan Kettering Cancer Centre (MSKCC), Briganti 2012, Briganti 2017, Briganti 2019, Partin 2016 and Yale models were evaluated using receiver-operating characteristic curve analysis (area under the curve [AUC]), calibration plots, and decision-curve analysis.

Results: Overall, 1158 patients (9.6%) had LNI, with a mean of 17.7 and 3.2 resected and positive nodes, respectively. No significant differences in AUCs were observed between the MSKCC (0.79), Briganti 2012 (0.79), Partin 2016 (0.78), Yale (0.80), Briganti 2017 (0.81) and Briganti 2019 (0.76) models. A direct comparison of older models showed that better discrimination was achieved with the MSKCC and Briganti 2012 nomograms. A tendency for underestimation was seen for all the older models, whereas the Briganti 2017 and 2019 nomograms tended to overestimate LNI risk. Decision-curve analysis showed a net benefit for all models, with a lower net benefit for the Partin 2016 and Briganti 2019 models. ePLND-related complications were experienced by 1027 patients (8.9%), and 12.6% of patients with pN1 disease.

Conclusions: The currently available nomograms have similar performances and limitations in the prediction of LNI. Miscalibration was present, however, for all nomograms showing a net benefit. In patients with only systematic biopsy, the MSKCC and Briganti 2012 nomograms were superior in the prediction of LNI.
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http://dx.doi.org/10.1111/bju.15220DOI Listing
March 2021

Transperitoneal vs retroperitoneal minimally invasive partial nephrectomy: comparison of perioperative outcomes and functional follow-up in a large multi-institutional cohort (The RECORD 2 Project).

Surg Endosc 2021 08 27;35(8):4295-4304. Epub 2020 Aug 27.

Division of Urology, Department of Oncology- School of Medicine, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy.

Background: Aim of this study was to evaluate and compare perioperative outcomes of transperitoneal (TP) and retroperitoneal (TR) approaches in a multi-institutional cohort of minimally invasive partial nephrectomy (MI-PN).

Material And Methods: All consecutive patients undergone MI-PN for clinical T1 renal tumors at 26 Italian centers (RECORd2 project) between 01/2013 and 12/2016 were evaluated, collecting the pre-, intra-, and postoperative data. The patients were then stratified according to the surgical approach, TP or RP. A 1:1 propensity score (PS) matching was performed to obtain homogeneous cohorts, considering the age, gender, baseline eGFR, surgical indication, clinical diameter, and PADUA score.

Results: 1669 patients treated with MI-PN were included in the study, 1256 and 413 undergoing TP and RP, respectively. After 1:1 PS matching according to the surgical access, 413 patients were selected from TP group to be compared with the 413 RP patients. Concerning intraoperative variables, no differences were found between the two groups in terms of surgical approach (lap/robot), extirpative technique (enucleation vs standard PN), hilar clamping, and ischemia time. Conversely, the TP group recorded a shorter median operative time in comparison with the RP group (115 vs 150 min), with a higher occurrence of intraoperative overall, 21 (5.0%) vs 9 (2.1%); p = 0.03, and surgical complications, 18 (4.3%) vs 7 (1.7%); p = 0.04. Concerning postoperative variables, the two groups resulted comparable in terms of complications, positive surgical margins and renal function, even if the RP group recorded a shorter median drainage duration and hospital length of stay (3 vs 2 for both variables), p < 0.0001.

Conclusions: The results of this study suggest that both TP and RP are feasible approaches when performing MI-PN, irrespectively from tumor location or surgical complexity. Notwithstanding longer operative times, RP seems to have a slighter intraoperative complication rate with earlier postoperative recovery when compared with TP.
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http://dx.doi.org/10.1007/s00464-020-07919-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263535PMC
August 2021
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