Abstract Context There is uncertainty regarding the oncologic effectiveness of kidney-sparing surgery (KSS) compared with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). ...Objective To systematically review the current literature comparing oncologic outcomes of KSS versus RNU for UTUC. Evidence acquisition A computerised bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of KSS versus RNU. Approaches considered for KSS were segmental ureterectomy (SU) and ureteroscopic (URS) or percutaneous (PC) management. Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we identified 22 nonrandomised comparative retrospective studies published between 1999 and 2015 that were eligible for inclusion in this systematic review. A narrative review and risk-of-bias (RoB) assessment were performed using cancer-specific survival (CSS) as the primary end point. Evidence synthesis Seven studies compared KSS overall ( n = 547) versus RNU ( n = 1376). Information on the comparison of SU ( n = 586) versus RNU ( n = 3692), URS ( n = 162) versus RNU ( n = 367), and PC ( n = 66) versus RNU ( n = 114) was available in 10, 5, and 2 studies, respectively. No significant difference was found between SU and RNU in terms of CSS or any other oncologic outcomes. Only patients with low-grade and noninvasive tumours experienced similar CSS after URS or PC when compared with RNU, despite an increased risk of local recurrence following endoscopic management of UTUC. The RoB assessment revealed, however, that the analyses were subject to a selection bias favouring KSS. Conclusions Our systematic review suggests similar survival after KSS versus RNU only for low-grade and noninvasive UTUC when using URS or PC. However, selected patients with high-grade and invasive UTUC could safely benefit from SU when feasible. These results should be interpreted with caution due to the risk of selection bias. Patient summary We reviewed the studies that compared kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma. We found similar oncologic outcomes for favourable tumours when using ureteroscopic or percutaneous management, whereas indications for segmental ureterectomy could be extended to selected cases of aggressive tumours.
Urothelial carcinoma of the bladder (UC) has a poor prognosis, partly because of chemotherapy resistance. Molecular classifications have shown their interest and can help to offer personalized ...treatment. In this study, we evaluated the feasibility of an immunohistochemical study to divide advanced UC into clinico-pathological-molecular subgroups and evaluate phenotypic correspondence between primary UC and matched lymph node metastases (LMN). An eight-antibody immunohistochemical panel was performed on UC and matched LMN from patients treated with radical cystectomy. One hundred eighty-seven UCs (100 pN0 tumor and 87 pN+ tumor) were tested. Multiple correspondence analysis showed that UC expressing GATA3 also expressed FOXA1 (
p
= 0.010) and did not stain for CK5/6 (
p
= 0.031) nor CK14 (
p
= 0.003). UC expressing CK14 coexpressed CK5/6 (
p
< 0.0001), had high Ki67 (
p
= 0.010) and no GATA3 (
p
= 0.003) nor FOXA1 (
p
= 0.011) expression. Loss of expression of STAG2 was associated with high Ki67 (
p
= 0.001). Sixty-seven percent of CK5/6 CK14+ GATA3 FOAXA1− patients had high Ki67 expression vs 37% of GATA3 FOXA1+ CK5/6 CK14− patients (
p
= 0.024). The majority of CK5/6 CK14+ GATA3 FOAXA1− patients (92%) had advanced disease (pT3-pT4) whilst 86% of pT1-T2 cases were GATA3 FOXA1+ CK5/6 CK14− (
p
= 0.041). Differential antigen expression between 63 pN+ primary tumors and their corresponding LNM showed the following concordance percentages: p53 (76%), p63 (75%), CK5/6 (65%), CK14 (89%), GATA3 (75%), FOXA1 (68%), STAG2 (65%), and Ki-67 (71%). These results support the interest of immunohistochemistry for subtype profiling in metastatic UC, using CK5/6, CK14, GATA3, and FOXA1, highlighting also few phenotypical modifications when tumor spreads to lymph nodes.
PURPOSE OF REVIEWDuring the last 15 years several updates in the Gleason grading have been made. With the help of pertinent research results pathologists have gained a better insight into the ...meanings of several prostate cancer (PCa) patterns and know better how to classify them in the Gleason grade system.
RECENT FINDINGSDuring the last years PCa with cribriform architecture has be given much attention. Many data have also been published about the meaning of comedonecrosis and its relationship with Gleason pattern 4 and 5. The correlationship between comedonecrosis and intraductal PCa has also been highlighted in the recent literature. Intraductal PCa is one of the most described topics at the moment with implications to treatment such as radiation therapy. We also highlight several practical issues such as the differences of grading in prostate biopsies and prostatectomies and describe the problematic of reporting a minor high-grade pattern.
SUMMARYMany new and recent data have allowed to refine diagnosis in PCa and improve the patientsʼs treatment. We show that comedonecrosis can be overgraded and insist on the implication with cribriform and intraducatal carcinomas. Furthermore, we describe the importance of these PCa types especially in the consideration of further treatment.
Isolated pancreatic metastases of renal cell carcinoma (IsPMRCC) are a rare manifestation of metastatic, clear-cell renal cell carcinoma (RCC) in which distant metastases occur exclusively in the ...pancreas. In addition to the main symptom of the isolated occurrence of pancreatic metastases, the entity surprises with additional clinical peculiarities: (a) the unusually long interval of about 9 years between the primary RCC and the onset of pancreatic metastases; (b) multiple pancreatic metastases occurring in 36% of cases; (c) favourable treatment outcomes with a 75% 5-year survival rate; and (d) volume and growth-rate dependent risk factors generally accepted to be relevant for overall survival in metastatic surgery are insignificant in isPMRCC. The genetic and epigenetic causes of exclusive pancreatic involvement have not yet been investigated and are currently unknown. Conversely, according to the few available data in the literature, the following genetic and epigenetic peculiarities can already be identified as the cause of the protracted course: 1. high genetic stability of the tumour cell clones in both the primary tumour and the pancreatic metastases; 2. a low frequency of copy number variants associated with aggressiveness, such as 9p, 14q and 4q loss; 3. in the chromatin-modifying genes, a decreased rate of PAB1 (3%) and an increased rate of PBRM1 (77%) defects are seen, a profile associated with a favourable course; 4. an increased incidence of KDM5C mutations, which, in common with increased PBRM1 alterations, is also associated with a favourable outcome; and 5. angiogenetic biomarkers are increased in tumour tissue, while inflammatory biomarkers are decreased, which explains the good response to TKI therapy and lack of sensitivity to IT.
Management of men with penile squamous cell carcinoma (PSCC) who have high-risk features following radical inguinal lymphadenectomy (ILND) remains controversial. European Association of Urology ...guidelines state that adjuvant inguinal radiotherapy (AIRT) is “not generally recommended”. Despite this, many centres continue to offer AIRT to a subset of men.
To undertake a systematic review of the evidence on AIRT in node-positive men with PSCC.
A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with no language or date restriction. Inclusion criteria were men with PSCC, pathologically staged inguinal node positive after ILND. The intervention included ILND with AIRT compared with ILND alone. Primary outcomes were relapse-free survival and toxicity. Risk of bias assessment was undertaken.
A total of 913 abstracts were identified and screened independently by two reviewers. Seven studies were eligible for inclusion: six full-text manuscripts and one conference abstract. All were retrospective series and at a high risk of bias. The selected studies included 1605 men. Indications for AIRT varied but were typically involvement of two or more inguinal nodes or extranodal extension. Regional recurrence rate following AIRT was reported at 10–91.7%. Only one study reported on toxicity. Two studies compared recurrence and survival between men who received and who did not receive AIRT, with no significant difference (p>0.05).
The evidence indicates that men treated with AIRT do not gain benefit with respect to relapse or survival. Uncertainty remains due to the retrospective nature and high risks of bias across the evidence. Given the lack of evidence supporting AIRT, it cannot be recommended for routine practice.
Men with penile cancer who have involvement of the inguinal lymph nodes are at a high risk of cancer recurrence and death. We reviewed the literature to see if radiation treatment after removal of the nodes provided benefit. We did not find any good-quality evidence supporting this treatment, and hence it cannot be recommended.
The published evidence on adjuvant inguinal radiotherapy following radical inguinal lymphadenectomy in men with penile cancer is limited and at a high risk of bias. The evidence identified failed to demonstrate any evidence of a recurrence or survival benefit.
Intraductal carcinoma of the prostate (IDC-P) has emerged as a distinct entity with significant clinical implications in prostate cancer (PCa) management. Despite historically being considered an ...extension of invasive PCa, IDC-P shows unique biological characteristics that challenge traditional diagnostic and therapeutic settings. This review explores the clinical management of IDC-P. While the diagnosis of IDC-P relies on specific morphological criteria, its detection remains challenging due to inter-observer variability. Emerging evidence underscores the association of IDC-P with aggressive disease and poor clinical outcomes across various PCa stages. However, standardized management guidelines for IDC-P are lacking. Recent studies suggest considering adjuvant and neoadjuvant therapies in specific patient cohorts to improve outcomes and tailor treatment strategies based on the IDC-P status. However, the current level of evidence regarding this is low. Moving forward, a deeper understanding of the pathogenesis of IDC-P and its interaction with conventional PCa subtypes is crucial for refining risk stratification and therapeutic interventions.
This Seminar presents the current best practice for the diagnosis and management of bladder cancer. The scope of this Seminar ranges from current challenges in pathology, such as the evolving ...histological and molecular classification of disease, to advances in personalised medicine and novel imaging approaches. We discuss the current role of radiotherapy, surgical management of non-muscle-invasive and muscle-invasive disease, highlight the challenges of treatment of metastatic bladder cancer, and discuss the latest developments in systemic therapy. This Seminar is intended to provide physicians with knowledge of current issues in bladder cancer.
Although pathology is the gold standard for confirming the diagnosis of prostate cancer (PCa), several marker for diagnosis may be useful and will helpin doubtful cases to confirm the diagnosis of ...PCa. Therfore it is important to spread the knowledge of immunomarker, in order to improve the clinicians understanding of stains and their usefulness. Like in other organs, clinicians and pathologists would like not to rely only on pathological criteria such as PSA, Gleason score, tumor size and pT stage, but also on tumor stains, permitting to predict prognosis and patients outcome, especially in patients with intermediate risk. Many markers have been proposed, but none is at the very moment approuved for current use.
In bladder cancer patients treated with radical cystectomy (RC), controversy exists regarding the impact of the annual hospital volume (HV) and/or surgeon volume (SV) on oncological outcomes and ...quality of care.
A systematic review was performed to evaluate the impact of HV and SV on clinical outcomes. Primary outcomes included in-hospital, 30-d, and 90-d mortality. Secondary outcomes included complications, long-term survival, positive surgical margin rate, lymphadenectomy performance, length of hospital stay, neobladder performance, and blood loss/transfusion rate.
Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched. Comparative studies published after the year of 2000 including patients who underwent RC for bladder cancer were eligible for inclusion. Partial cystectomy was an exclusion criterion. Risk of bias (RoB) assessment was performed according to the ROBINS-1 tool.
After screening of 1190 abstracts, 39 studies recruiting 549 542 patients were included. All studies were retrospective observation cohort studies (level of evidence 3). Twenty-two studies reported on HV only, six studies on SV only, and 12 on both. Higher HV, specifically an HV of >10, was associated with improved primary and secondary outcomes in most studies. In addition, there is some evidence that an HV of >20 improves outcomes. For SV, limited and conflicting data are reported. Most studies had moderate to high RoB. The results were synthesized narratively.
Acknowledging the lower level of evidence, HV is likely associated with in-hospital, 30- and 90-d mortality, as well as the secondary outcomes assessed. Based on this study, the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel recommends hospitals to perform at least 10, and preferably >20, RCs annually or refer the patient to a center that reaches this number. For SV, limited and conflicting data are available. The available evidence suggests HV rather than SV to be the main driver of perioperative outcomes.
Current literature suggests that the number of bladder removal operations per hospital per year is associated with postoperative survival as well as the quality of care provided.
Based on this systematic review, the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel recommends hospitals to perform at least 10 and preferably >20 radical cystectomies annually or refer patients to a center that performs this number. Hospital volume is likely associated with lower in-hospital, 30-d, and 90-d mortality as well as more favorable secondary outcomes (complications, long-term survival, positive surgical margin rate, lymphadenectomy performance, length of hospital stay, neobladder performance, and blood loss/transfusion rates). For surgeon volume, the evidence is less convincing and the main driver of outcomes seems to be the hospital volume. Notwithstanding the evidence limitations, this systematic review includes data of more than 500000 unique patients.
The new World Health Organization classification of tumours of the urinary system and male genital organs (4th edn) has several changes from previous versions, and was published in January 2016. New ...pathways have been discovered in the development of bladder cancer, and were included in this new classification. Guidance from the International Collaboration on Cancer Reporting (ICCR) helped to clarify open questions, in conjunction with the new classification. The histological groups of urothelial carcinoma evolved. Grading remained the same, despite controversy among European urologists. Substaging of pT1 tumours is recommended for the first time, and the ICCR has made recommendations on how to report this. Furthermore, worldwide advice has been published on the use of immunohistochemistry, and recommendations have been made to try to standardize the handling of bladder cancer from a histopathological point of view. At a molecular level, bladder cancer groups have been stratified, and an upcoming molecular classification permits a novel view of this malignancy. This review will try to summarize the most important changes.
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