This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC).
To provide practical evidence-based recommendations and ...consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment.
A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted.
Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non–muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in “fit” patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1–negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/.
This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice.
The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease.
Radical cystectomy with urinary diversion remains the mainstay of managing muscle-invasive bladder cancer (MIBC). The use of neoadjuvant chemotherapy (NAC) has improved overall survival rates, but selection of patients who will benefit most from NAC remains challenging. In case bladder-preserving strategies are considered, patient stratification according to their risk profile is imperative and management should be discussed in a multidisciplinary team. As yet, there are no validated prognostic molecular markers to guide the clinical management of MIBC. In a metastatic setting, cisplatin-based chemotherapy remains the first choice in fit patients. In unfit patients, based on interim results from two on-going clinical trials, first-line treatment with pembrolizumab or atezolizumab for urothelial cancer is restricted to Programmed Death Ligand 1-positive patients only.
MiR-371a-3p predicts the presence of a macroscopic non-teratomatous germ cell tumour (GCT). We hypothesised that miR-371a-3p can also detect recurrence during active surveillance (AS) of stage I GCT.
...We prospectively collected serum samples of 33 men. Relative expression of serum miR-371a-3p levels was determined at each follow-up visit using real-time quantitative reverse transcription-polymerase chain reaction.
Recurrence was detected using standard follow-up investigations in 10/33 patients (30%) after a median of 7 months. Directly after orchiectomy, miR-371a-3p levels were not elevated in any of the 15 patients with available post-orchiectomy samples. However, all ten recurring patients exhibited increasing miR-371a-3p levels during follow-up, while miR-371a-3p levels remained non-elevated in all but one patient without recurrence. MiR-371a-3p detected recurrences at a median of 2 months (range 0-5) earlier than standard follow-up investigations.
MiR-371a-3p levels immediately post orchiectomy are not predictive for recurrences and unfortunately cannot support decision-making for AS vs. adjuvant treatment. However, miR-371a-3p detects recurrences reliably and earlier than standard follow-up investigations. If this can be confirmed in larger cohorts, monitoring miR-371a-3p could replace surveillance imaging in seminomatous GCT and reduce the amount of imaging in non-seminomatous GCT. Earlier detection of disease recurrence may also reduce the overall treatment burden.
Testicular cancer is an important disease with increasing incidence and a high burden of morbidity and mortality in young men worldwide. Histological examination of the testicular tissue after ...orchiectomy plays an important role alongside patient history, imaging, clinical presentation and laboratory parameters. Surgical procedures and chemotherapeutic treatment provide a high chance of cure in early stages, though some patients in advanced stages belonging to a poor risk group experience cancer-related death. Though conventional serum-based tumor markers, including α-fetoprotein (AFP), the β-subunit of human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH), are useful as prognostic and diagnostic biomarkers, unfortunately, these tumor markers only have a sensitivity of about 60%, and in pure seminoma even lower with about 20%. Therefore, the development of new tumor markers is an important and intensively ongoing issue. The analysis of epigenetic modification and non-coding RNA microRNAs (miRNAs) are carrying most promising potential as tumor markers in future. miRNAs are small RNAs secreted by testicular tumor cells and circulate and be measurable in body fluids. In recent years, miRNAs of the miR-371-373 cluster in particular have been identified as potentially superior tumor markers in testicular cancer patients. Studies showed that miR-371a-3p and miR-302/367 expression significantly differ between testicular tumors and healthy testicular tissue. Several studies including high prospective multi-center trials clearly demonstrated that these miRNAs significantly exceed the sensitivity and specificity of conventional tumor markers and may help to facilitate the diagnosis, follow-up, and early detection of recurrences in testicular cancer patients. In addition, other miRNAs such as miR-223-3p, miR-449, miR-383, miR-514a-3p, miR-199a-3p, and miR-214 will be discussed in this review. However, further studies are needed to identify the value of these novel markers in additional clinical scenarios, including the monitoring in active surveillance or after adjuvant chemotherapy, but also to show the limitations of these tumor markers. The aim of this review is to give an overview on the current knowledge regarding the relevance of non-coding miRNAs as biomarkers in testicular cancer.
Conventional-dose chemotherapy (CDCT) and high-dose chemotherapy (HDCT) may both be successfully used as salvage treatment for patients with metastatic germ cell tumors (GCTs) who experience ...progression with first-line treatment.
Data on 1,984 patients with GCTs who experienced progression after at least three cisplatin-based cycles and were treated with either cisplatin-based CDCT or carboplatin-based HDCT chemotherapy were collected from 38 centers or groups worldwide. Of 1,984 patients, 1,594 (80%) were eligible, and among the eligible patients, 1,435 (90%) could reliably be classified into one of the following five prognostic categories based on prior prognostic classification: very low (n = 76), low (n = 257), intermediate (n = 646), high (n = 351), and very high risk (n = 105). Within each of the five categories, the progression-free survival (PFS) and overall survival (OS) after CDCT and HDCT were compared using the Cox model adjusted for significant distributional differences between important variables.
Overall, 773 patients received CDCT, and 821 patients received HDCT. Both treatment modalities were used with similar frequencies within each prognostic category. The hazard ratio for PFS was 0.44 (95% CI, 0.39 to 0.51) stratified on prognostic category, and the hazard ratio for OS was 0.65 (95% CI, 0.56 to 0.75), favoring HDCT. These results were consistent within each prognostic category except among low-risk patients, for whom similar OS was observed between the two treatment groups.
This retrospective analysis suggests a benefit from HDCT given as intensification of first salvage treatment in male patients with GCTs and emphasizes the need for another prospective randomized trial comparing CDCT to HDCT in this patient population.
Background Two thirds of patients with germ-cell cancer (GCC) present as clinical stage I (CSI). Following orchiectomy, active surveillance (AS) has become their standard management. However, 15-50% ...of patients eventually relapse with metastatic disease after AS. Relapses need to be detected early in order to achieve cure and avoid overtreatment. Methods We retrospectively analyzed consecutive GCC patients treated at two Swiss academic centers between 2010 and 2020. Patients with stage IS and extragonadal primaries were excluded. We compared disease characteristics and survival outcomes of patients relapsed from initial CSI to patients with de novo metastatic disease. Primary endpoint was the IGCCCG category at the time of relapse. Main secondary endpoints were progression-free survival (PFS) and overall survival (OS). Results We identified 360 GCC patients with initial CSI and 245 de novo metastatic patients. After a median follow-up of 47 months, 81 of 360 (22.5%) CSI patients relapsed: 41 seminoma (Sem) and 40 non-seminoma (NSem) patients. All Sems relapsed in the IGCCCG good prognosis group. NSem relapsed with good 29/40 (72.5%) and intermediate 11/40 (27.5%) prognostic features; 95.1% of relapses occurred within five years post-orchiectomy. Only 3 relapsed NSem patients died from metastatic disease. Five-year OS for relapsed CSI patients was 100% for Sem and 87% (95% CI: 61-96%) for NSem patients; five-year PFS was 92% (95% CI: 77-97) and 78% (95% CI: 56-90) for Sem and NSem, respectively. When stratified by IGCCCG prognostic groups, good risk relapsed patients had a trend towards better OS and PFS as compared to de novo metastatic patients. Conclusions GCC patients who relapse after initial CSI can be detected early by active surveillance and have an excellent survival. Keywords: Testicular cancer, Germ-cell cancer, Clinical stage I, Active surveillance, Follow-up, Relapse, IGCCCG prognostic group
Purpose
Thoracic growing teratoma syndrome (TGTS) is a rare disease in patients with germ cell tumors. Other than a few case reports and a limited number of case series, studies of this topic are not ...available.
Methods
We retrospectively analyzed the data from our patients who received surgery for TGTS between 1999 and 2016. Descriptive statistical analyses were performed to analyze the characteristics of the patients, tumors, and short-term outcomes. Furthermore, the long-term outcomes and survival curves were analyzed using the Kaplan–Meier method.
Results
Twenty-nine patients underwent surgery for TGTS. The median age was 32 years (range: 19–50 years). All patients received cisplatin-based chemotherapy. Many of the patients had multilocalized TGTS (
n
= 10). The median tumor size was 64.5 mm (range 10-210 mm). In all cases, R0 resection was achieved. The minor morbidity, major morbidity, and mortality rates were 3.4%, 6.9%, and 0%, respectively. Altogether, 28 patients were included in the long-term follow-up analysis, with a median follow-up time of 94 months (13–237 months). The 5-, 10-, and 15-year survival rates were 93%, 93%, and 84%, respectively.
Conclusions
TGTS may occur in multiple localizations and grow to a large tumor size. The resection of TGTS can be performed with low morbidity and mortality rates and is associated with good overall survival after complete resection. Important are an early detection and knowledge of the systemic treatment options by the oncologist and urologist, as well as a thoracic surgeon with a large experience in extended thoracic resections.
Purpose
Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumor, and currently, there are no published treatment recommendations.
Methods
We performed a systematic literature review and ...synthesized clinical presentation, clinicopathological factors associated with metastatic disease, treatment options, and outcomes in men with MTVT.
Results
We included 170 publications providing data on 275 patients. Metastatic disease occurred in 84/275 (31%) men with malignant MTVT: Most common sites included retroperitoneal lymph nodes (LNs) (40/84, 48%), lungs (30/84, 36%), and inguinal LNs (23/84, 27%).
Invasion of the spermatic cord or scrotum was the only risk factor for local recurrence odds ratio (OR) 3.21, 95% confidence interval (CI) 1.36–7.57. Metastatic disease was associated with age ≥ 42 years (OR 3.02, 95% CI 1.33–6.86), tumor size ≥ 49 mm (OR 6.17, 95% CI 1.84–20.74), presence of necrosis (OR 8.31, 95% CI 1.58–43.62), high mitotic index (OR 13.36, 95% CI 1.53–116.51) or angiolymphatic invasion (OR 3.75, 95% CI 1.02–13.80), and local recurrence (OR 4.35, 95% CI 2.00–9.44). Complete remission in the metastatic setting was observed in five patients, most of whom were treated with multimodal therapy. Median survival in patients with metastatic disease was 18 months (IQR 7–43).
Conclusion
Malignant MTVT is a rare but aggressive disease. Since local recurrence is a risk factor for metastatic progression, we recommend aggressive local treatment. Survival and response to any treatment in the metastatic setting are limited.
Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is an integral part of the management of patients with metastatic non-seminoma and residual masses >1 cm after chemotherapy.
To ...assess perioperative complications and oncological outcomes at two major referral centres in Switzerland.
This was a retrospective chart review of 136 patients with non-seminoma who underwent PC-RPLND between 2010 and 2020 at the university hospitals of Bern and Zürich. Patient, treatment and tumour characteristics as well as the types and frequencies of intra- and postoperative complications were registered and compared using the chi-square test. Oncological outcomes consisted of the time and location of relapses as well as progression-free and overall survival, which were compared using the log-rank test.
Overall, 70 patients from Bern and 66 patients from Zürich were included; 5 patients had a previous retroperitoneal lymph node dissection (RPLND) (2 Bern, 3 Zürich). Vascular injuries were the most frequent intraoperative complication, occurring in 27/136 (19.9%) patients. Postoperative complications were observed in 42/136 (30.9%) patients, ileus being the most common. Perioperative mortality was 2.2%. A retroperitoneal mass ≥50 mm was significantly associated with intraoperative complications (p = 0.004) and increased resource demands (p = 0.021). Postoperative morbidity was higher according to age at post-chemotherapy retroperitoneal lymph node dissection ≥40 years (p = 0.028) and retroperitoneal mass ≥20 mm (p = 0.005). The median follow-up time was 37 months (interquartile range IQR 18-64 months). The median progression-free survival at 5 years was 76% (95% confidence interval CI: 64-85%) in Bern and 69% (95% CI: 54-80%) in Zürich (p = 0.464). The median overall survival at 5 years was 88% (95% CI: 76-94%) in Bern and 77% (95% CI: 60-87%) in Zürich (p = 0.335). Patients with progressive disease or a tumour marker increase before retroperitoneal lymph node dissection had significantly inferior progression-free and overall survival compared to non-progressing patients. The presence of teratoma in resected specimens did not confer inferior survival probabilities compared to necrosis only, whereas the presence of vital undifferentiated tumour conferred inferior progression-free and overall survival. Patients with a previous retroperitoneal lymph node dissection and patients operated for late relapses >2 years after chemotherapy also had significantly inferior progression-free and overall survival.
We found a relevant rate of severe perioperative complications at PC-RPLND at even experienced high-volume centres. The oncological outcomes at two major university urological centres in Switzerland were similar and determined by preoperative risk factors and intraoperative histology.
To evaluate the long-term survival rates in patients with relapsed or refractory germ cell tumors (GCTs) after single or sequential high-dose chemotherapy (HDCT).
Between November 1999 and November ...2004, 211 patients with relapsed or refractory GCT were randomly assigned to treatment with either one cycle of cisplatin 100 mg/m(2), etoposide 375 mg/m(2), and ifosfamide 6 g/m(2) (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m(2) and etoposide 1,500 mg/m(2) (CE, arm A) or three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m(2), etoposide 1,800 mg/m(2), and cyclophosphamide 6,400 mg/m(2) (CEC, arm B) followed by autologous stem-cell reinfusion. Long-term progression-free survival (PFS) and overall survival (OS) 6 years after random assignment of the last patient were compared by using the log-rank test.
Overall, 108 and 103 patients were randomly assigned to arms A and B, respectivelyl. The study was stopped prematurely because of excess treatment-related mortality in arm B (14%) compared with that in arm A (4%; P = .01). As of December 2010, nine (5%) of 211 patients were lost to follow-up; 94 (45%) of 211 are alive and 88 (94%) of 94 patients are progression free. Five-year PFS is 47% (95% CI, 37% to 56%) in arm A and 45% (95% CI, 35% to 55%) in arm B (hazard ratio HR, 1.16; 95% CI, 0.79 to 1.70; P = .454). Five-year OS is 49% (95% CI, 40% to 59%) in arm A and 39% (95% CI, 30% to 49%) in arm B (HR, 1.42; 95% CI, 0.99 to 2.05; P = .057).
Patients with relapsed or refractory GCT achieve durable long-term survival after single as well as sequential HDCT. Fewer early deaths related to toxicity translated into superior long-term OS after sequential HDCT.
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