Probably, patients with de novo (synchronous) and recurrent (metachronous) oligometastatic hormone-sensitive prostate cancer have different oncologic outcomes. Thus, we are challenged with different ...scenarios in clinical practice, where different treatment options may apply. In the last years, several prospective studies have focused on the treatment of patients with de novo oligometastatic hormone-sensitive prostate cancer. Not only the addition of systemic therapeutic treatments, such as chemotherapy with docetaxel, abiraterone, enzalutamide, and apalutamide, next to androgen deprivation therapy, demonstrated to improve outcomes in these patients but also local therapy of the primary has been demonstrated to improve outcomes of low-volume metastatic disease. Next to radiotherapy, also radical prostatectomy has been reported as a feasible and safe treatment option. Additional metastasis-directed therapy in de novo metastatic disease is currently examined by four trials. In the recurrent metastatic setting, less data are available, and it remains uncertain if patients can be treated in the same way as synchronous oligometastatic disease. Metastasis-directed therapy has demonstrated to prolong outcomes, while data on survival are still missing.
Introduction: The aim of the study was to examine cancer-specific mortality (CSM) of unconventional urethral cancers. Methods: Within the SEER (2004–2016) database, we analyzed CSM of 165 patients ...with unconventional urethral-cancer histology. Kaplan-Meier plots were used to test the effect of unconventional histologies in urethral cancer on CSM. Results: Of 165 eligible patients, the Mullerian type accounted for 55 (33.3%) versus melanocytic (26.7%) versus neuroendocrine 25 (15.2%) versus lymphoma 22 (13.3%) versus mesenchymal/sarcoma 15 (9.1%) versus spindle cell 4 (2.1%) patients. Median age at diagnosis was 81 years in spindle cell, 75 in melanocytic, 74 in neuroendocrine and mesenchymal/sarcoma, 67 in lymphoma, and 62 years Mullerian type (p < 0.001). Of all, 116 (70.3%) were female. The Mullerian type exhibited the highest female ratio (96.4%) versus the lowest female ratio in neuroendocrine (24.0%). The Mullerian type was most frequent in African-American females. In Caucasian females, the melanocytic type was most frequent (49.1%). In African-American (38.9%) and Caucasian males (33.3%), neuroendocrine histology was most frequent. Three-year CSM was, respectively, 27.5%, 23.1% 22.3%, 20.5%, and 16.1% for melanocytic, mesenchymal/sarcoma, Mullerian type, neuroendocrine, and lymphoma histology. Median cancer-specific survival was 106 versus 10 months for combined nonmetastatic versus metastatic nonconventional histologies. Conclusion: Important age, sex, racial/ethnic group distribution, and survival differences exist between each unconventional urethral-cancer histological subtypes.
This study aimed to evaluate the impact of preoperative double-J stent (DJ) in pyeloplasty patients on perioperative complications, recurrence, and quality of life (QoL).
Pyeloplasties due to ...ureteropelvic junction obstructions between January 2010 and December 2020 were consecutively identified. A standardized follow-up questionnaire was used. Tabulation was made according to preoperative DJ versus no DJ. Subgroup analyses addressed primary robotic pyeloplasties.
Of 95 pyeloplasty patients, 62% received a preoperative DJ. Patients with preoperative DJ exhibited higher rates of Clavien-Dindo (CD) 2 (22 vs. 11%) complications, but not of CD3 (8.5 vs. 8.3%, p = 0.5). After a median follow-up of 61 months, 9 patients exhibited a recurrence, of whom 7 had a preoperative DJ. In QoL assessment, comparable findings were made between patients with and without preoperative DJ. In robotic pyeloplasty patients (n = 73), patients with preoperative DJ (58%, n = 42) experienced higher CD3 complication rates, compared to patients without preoperative DJ (12 vs. 6.5%). Moreover, higher rates of recurrences were observed in preoperative DJ patients (12 vs. 3.2%).
In a contemporary pyeloplasty cohort, the midterm success rate was good with 91%. Our findings suggest that preoperative DJ is associated with higher recurrence rates. However, QoL did not differ between patients with and without preoperative DJ.
We aimed to test for survival differences between testicular pure teratoma vs. mixed germ cell tumor (GCT) patients in a stage-specific fashion. Pure teratoma and mixed GCT in primary tumor specimens ...were identified within the Surveillance, Epidemiology, and End Results database (2004-2019). Kaplan-Meier curves depicted five-year overall survival (OS) and subsequently, cumulative incidence plots depicted cancer-specific mortality (CSM) and other-cause mortality (OCM) in a stage-specific fashion. Multivariable competing risks regression (CRR) models were used. Of 9049 patients, 299 (3%) had pure teratoma. In stage I, II and III, five-year OS rates differed between pure teratoma and mixed GCT (stage I: 91.6 vs. 97.2%,
< 0.001; stage II: 100 vs. 95.9%,
< 0.001; stage III: 66.8 vs. 77.8%,
= 0.021). In stage I, survival differences originated from higher OCM (6.4 vs. 1.2%;
< 0.001). Conversely in stage III, survival differences originated from higher CSM (29.4 vs. 19.0%;
= 0.03). In multivariable CRR models, pure teratoma was associated with higher OCM in stage I (Hazard Ratio (HR): 4.83;
< 0.01). Conversely, in stage III, in multivariable CRR models, pure teratoma was associated with higher CSM (HR: 1.92;
= 0.04). In pure teratoma, survival disadvantage in stage I patients relates to OCM. Survival disadvantage in stage III pure teratoma originates from higher CSM.
Abstract
Objectives
To test for differences in overall and recurrence-free survival between laparoscopic and open surgical approaches in patients undergoing radical nephroureterectomy (RNU) for upper ...tract urothelial carcinoma (UTUC).
Materials and methods
We retrospectively identified patients treated for UTUC from 2010 to 2020 from our institutional database. Patients undergoing laparoscopic or open RNU with no suspicion of metastasis (cM0) were for the current study population. Patients with suspected metastases at diagnosis (cM1) or those undergoing other surgical treatments were excluded. Tabulation was performed according to the laparoscopic versus open surgical approach. Kaplan-Meier plots were used to test for differences in overall and recurrence-free survival with regard to the surgical approach. Furthermore, separate Kaplan-Meier plots were used to test the effect of preoperative ureterorenoscopy on overall and recurrence-free survival within the overall study cohort.
Results
Of the 59 patients who underwent nephroureterectomy, 29% (n = 17) underwent laparoscopic nephroureterectomy, whereas 71% (n = 42) underwent open nephroureterectomy. Patient and tumor characteristics were comparable between groups (
p
≥ 0.2). The median overall survival was 93 and 73 months in the laparoscopic nephroureterectomy group compared to the open nephroureterectomy group (
p
= 0.5), respectively. The median recurrence-free survival did not differ between open and laparoscopic nephroureterectomies (73 months for both groups;
p
= 0.9). Furthermore, the median overall and recurrence-free survival rates did not differ between patients treated with and without preoperative ureterorenoscopy.
Conclusions
The results of this retrospective, single-center institution showed that overall and recurrence-free survival rates did not differ between patients with UTUC treated with laparoscopic and open RNU. Furthermore, preoperative ureterorenoscopy before RNU was not associated with higher overall or recurrence-free survival rates.
: The impact of pure histological subtypes in testicular non-seminoma germ cell tumors on survival, specifically regarding pure embryonal carcinoma, is not well established. Therefore, this study ...aimed to test for differences between pure embryonal carcinoma and mixed germ cell tumor patients within stages I, II and III in a large population-based database.
: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify testicular pure embryonal carcinoma vs. mixed germ cell tumor patients. Cumulative incidence plots depicted cancer-specific mortality that represented the main endpoint of interest. Multivariable competing risks regression models tested for differences between pure embryonal carcinoma and mixed germ cell tumor patients in analyses addressing cancer-specific mortality and adjusted for other-cause mortality.
: Of 11,223 patients, 2473 (22%) had pure embryonal carcinoma. Pure embryonal carcinoma patients exhibited lower cancer-specific mortality relative to their mixed germ cell tumor counterparts for both stage III (13.9 vs. 19.4%;
< 0.01) and stage II (0.5 vs. 3.4%,
< 0.01), but not in stage I (0.9 vs. 1.6%,
= 0.1). In multivariable competing risks regression models, pure embryonal carcinoma exhibited more favorable cancer-specific mortality than mixed germ cell tumor in stage III (hazard ratio 0.71,
= 0.01) and stage II (hazard ratio 0.11,
< 0.01).
: Pure embryonal carcinoma exhibits a more favorable cancer-specific mortality profile relative to mixed germ cell tumor in stage II and III testicular cancers. Consequently, the presence of mixed germ cell tumor elements may be interpreted as a risk factor for cancer-specific survival.
Introduction and Objective
Identifying patients that benefit from cisplatin-based adjuvant chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC). The purpose of ...this study is to correlate “luminal” and “basal” type protein expression with histological subtypes, to investigate the prognostic impact on survival after adjuvant chemotherapy and to define molecular consensus subtypes of “double negative” patients (i.e., without expression of CK5/6 or GATA3).
Materials and Methods
We performed immunohistochemical (IHC) analysis of CK5/6 and GATA3 for surrogate molecular subtyping in 181 MIBC samples. The mRNA expression profiles for molecular consensus classification were determined in CK5/6 and GATA3 (double) negative cases using a transcriptome panel with 19.398 mRNA targets (HTG Molecular Diagnostics). Data of 110 patients undergoing radical cystectomy were available for survival analysis.
Results
The expression of CK5/6 correlated with squamous histological subtype (96%) and expression of GATA3 was associated with micropapillary histology (100%). In the multivariate Cox-regression model, patients receiving adjuvant chemotherapy had a significant survival benefit (hazard ratio
HR
: 0.19 95% confidence interval
CI
: 0.1–0.4,
p
< 0.001) and double-negative cases had decreased OS (
HR
: 4.07; 95%
CI
: 1.5–10.9,
p
= 0.005). Double negative cases were classified as NE-like (30%), stroma-rich (30%), and Ba/Sq (40%) consensus molecular subtypes and displaying different histological subtypes.
Conclusion
Immunohistochemical-based classification was associated with histological subtypes of urothelial MIBC. IHC markers like CK5/6 and GATA3 that are used in pathological routine could help to identify patients with basal and luminal tumor characteristics. However, a two-sided classification system might not sufficiently reflect the heterogeneity of bladder cancer to make treatment decisions. Especially the group of IHC-double negative cases, as further analyzed by mRNA expression profiling, are a heterogeneous group with different implications for therapy.
What's known on the subject? and what does the study add?: UroVysion™ is a multicolour fluorescence in situ hybridisation assay that detects DNA gain at chromosomes 3, 7 and 17 and loss at the 9p21 ...locus in exfoliated urothelial cells. This cell-based test is time-consuming and costly compared with voided urine cytology or other molecular markers for the early detection of bladder cancer. We determined copy number changes at chromosomes 3, 7 and 17 and at the 9p21 locus with UroVysion in a prospective screening study among chemical workers. Strong correlations between DNA gains yield a similar performance in detecting bladder cancer with just one of the probes for chromosomes 3, 7 or 17 instead of all, supporting the development of a simpler and cheaper assay.
To explore changes at chromosomes 3, 7, 17 and 9p21 in order to assess associations with bladder cancer for possible improvements of the UroVysion™ assay regarding screening.
In all, 1609 men took part in the prospective study UroScreen. Annual screening for bladder cancer was offered to male chemical workers with former exposure to aromatic amines as a voluntary surveillance programme between 2003 and 2010. In all, 191 434 cells in 6517 UroVysion tests were analysed for copy number variations (CNV) at chromosome 3, 7, 17 (gains) and 9p21 (deletions) in 1595 men. We assessed CNVs at single or multiple loci using polysomy indices (PIs, called multiple PI and PI 3, PI 7 and PI 17). We calculated Spearman's rank correlation coefficients (rs ) between these PIs and receiver operating characteristic (ROC) curves with areas under the curves (AUCs). We applied Cox regression to estimate hazard ratios (HRs) to assess the risk of developing bladder cancer.
Nine out of 21 bladder tumours detected in 20 participants ('cases') had a positive UroVysion test, including seven high-grade carcinomas and seven overlapping results with a positive cytology. Four cases with negative test results did not attend screening annually. No case was found because of a complete loss of 9p21 in at least 12 cells. There were strong correlations between pairwise combinations of gains at chromosome 3, 7 or 17, ranging between rs = 0.98 and rs = 0.99 in cases and between rs = 0.84 and rs = 0.88 in non-cases (P < 0.001). Associations were less pronounced with CNVs at 9p21 among cases and were lacking in non-cases. Estimates of the relative risk of DNA gain for developing a bladder tumour assessed with PIs (threshold 10% of cells) were 47.7 (95% confidence interval CI 18.3-124.1) for the multiple PI, 44.5 (95%CI 16.5-119.9) for PI 3, 34.7 (95%CI 13.1-92.1) for PI 7 and 52.4 (95%CI 20.7-132.6) for PI 17, as well as 7.9 (95%CI 3.0-20.6) for a complete loss of 9p21 (threshold 2.5% of cells), respectively. ROC analyses showed similar AUCs for multiple PI compared with PIs of single chromosomes 3, 7 and 17 (all AUCs between 0.79 and 0.80) and a lower AUC for a homozygous loss of 9p21 (AUC 0.72).
The UroVysion assay showed a reasonable performance in detecting bladder cancer in the present study population and shared positive test results with cytology, which is much cheaper. A simpler, faster and cheaper version of the UroVysion assay might rely on the very strong correlations between gains at chromosomes 3, 7 and 17, resulting in a similar performance in detecting bladder cancer with single-probe PIs compared with the full set of these probes. Loss of 9p21 was less predictive for developing bladder cancer in UroScreen.
Meticulous knowledge about the anatomy of the prostate and surrounding tissue represents a crucial and mandatory requirement during radical prostatectomy for reliable oncological and excellent ...replicable, functional outcomes. Since its introduction two decades ago, robotic-assisted laparoscopic radical prostatectomy (RALP) has evolved to become the predominant surgical approach in many industrialized countries.
To provide and highlight currently available literature regarding prostate anatomy and to help in improving oncological and functional outcomes in RALP.
PubMed database was searched using the following keywords: "robotic-assisted radical prostatectomy," "anatomy," "neurovascular bundle," "nerve," "periprostatic fascia," "pelvis," "sphincter," "urethra," "urinary incontinence," and "erectile dysfunction." Relevant articles and book chapters were critically reviewed and if eligible, they were included in this review.
New evidence in regards to prostatic anatomy and surgical approaches in RALP has been reported in recent years. Besides detailed anatomical studies investigating the meticulous structure of the fascial structures surrounding the prostate and neurovascular bundle preservation, debate about the optimal RALP approach is still ongoing, inspired by recent publications presenting promising functional outcomes following modifications in surgical approaches.
This review provides a detailed overview of the current knowledge of prostate anatomy, its surrounding tissue, and its influence on key surgical step development for RALP.
Objectives
Immune checkpoint blockade (IO) has revolutionised the treatment of metastatic renal cell carcinoma (mRCC). Early C‐reactive protein (CRP) kinetics, especially the recently introduced CRP ...flare‐response phenomenon, has shown promising results to predict IO efficacy in mRCC, but has only been studied in second line or later. Here, we aimed to validate the predictive value of early CRP kinetics for 1st‐line treatment of mRCC with αPD‐1 plus either αCTLA‐4 (IO+IO) or tyrosine kinase inhibitor (IO+TKI).
Methods
In this multicentre retrospective study, we investigated the predictive potential of early CRP kinetics during 1st‐line IO therapy. Ninety‐five patients with mRCC from six tertiary referral centres with either IO+IO (N = 59) or IO+TKI (N = 36) were included. Patients were classified as CRP flare‐responders, CRP responders or non‐CRP responders as previously described, and their oncological outcome was compared.
Results
Our data validate the predictive potential of early CRP kinetics in 1st‐line immunotherapy in mRCC. CRP responders, especially CRP flare‐responders, had significantly prolonged progression‐free survival (PFS) compared with non‐CRP responders (median PFS: CRP flare‐responder: 19.2 months vs. responders: 16.2 vs. non‐CRP responders: 5.6, P < 0.001). In both the IO+IO and IO+TKI subgroups, early CRP kinetics remained significantly associated with improved PFS. CRP flare‐response was also associated with long‐term response ≥ 12 months.
Conclusions
Early CRP kinetics appears to be a low‐cost and easy‐to‐implement on‐treatment biomarker to predict response to 1st‐line IO combination therapy. It has potential to optimise therapy monitoring and might represent a new standard of care biomarker for immunotherapy in mRCC.
In this multicentre study, we investigated the predictive potential of early serum C‐reactive protein (CRP) kinetics during 1st‐line immunotherapy in metastatic renal cell carcinoma (mRCC). Out of 95 patients with mRCC, those with significant CRP flare‐response or decrease in CRP levels had superior outcomes. This potential biomarker could improve therapy monitoring of mRCC and eventually also treatment stratification.
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