The natural history of untreated muscle‐invasive bladder cancer

Martini, Alberto; Sfakianos, John P.; Renström‐Koskela, Lotta; Mortezavi, Ashkan; Falagario, Ugo Giovanni; Egevad, Lars; Hosseini, A. Abolfazl; Mehrazin, Reza; Galsky, Matthew D.; Steineck, Gunnar; Wiklund, Peter

doi:10.1111/bju.14872

Cited by 84 publications

(47 citation statements)

References 26 publications

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“…Although perioperative complication rates range around 50% in our entire study cohort, we found acceptable perioperative complication rates, ranging well among the reported 24–61% [23-25]. However, if no treatment is offered to this group of patients, they are at high risk of developing metastatic disease and will most likely die due to the disease itself, as shown in the study of Martini et al [27]. Without any treatment, the risk of dying from MIBC as well as any other cause increases (HR 2.02 and 2.63, respectively) [27].…”

Section: Discussionsupporting

confidence: 82%

“…However, if no treatment is offered to this group of patients, they are at high risk of developing metastatic disease and will most likely die due to the disease itself, as shown in the study of Martini et al [27]. Without any treatment, the risk of dying from MIBC as well as any other cause increases (HR 2.02 and 2.63, respectively) [27]. While survival of the oldest-old is clearly limited, there is a significant benefit compared to a 2-year-survival rate of 14%, if left untreated [28].…”

Section: Discussionmentioning

confidence: 99%

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Is It Safe to Offer Radical Cystectomy to Patients above 85 Years of Age? A Long-Term Follow-Up in a Single-Center Institution

et al. 2020

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With a median age at diagnosis of 73 years, bladder cancer has the highest median age of all cancers. Age alone seems to be an independent risk factor for developing the disease with peak age advancing into the range of 85 years. As demographic changes will lead to an ever more aging population in western countries, incidence of advanced age malignancies will rise. We, therefore, analyzed a contemporary radical cystectomy (RC) series at a single high-volume center on patients undergoing RC for urothelial carcinoma of the bladder (UCB). We aim to evaluate the feasibility of RC in the oldest-old patient cohort by assessing perioperative complications and long-term outcome. Materials and Methods: We retrospectively analyzed data of 1,278 consecutive patients who underwent RC for UCB at our tertiary referral center between 2004 and 2019. A total of 408 patients were aged 75-97 years at the time of RC and were further divided into 2 groups: 75-84 years of age (group 1) and ≥85 years of age (group 2). Median follow-up was 23 months. Outcome was analyzed using the χ 2 test, Mann-Whitney U test, Kaplan-Meier method, and log-rank test. Results: Perioperative Clavien-Dindo grade ≥III complications were seen in 25.1% (92/366) of group 1 patients and 35.7% (15/42) of group 2 patients (p = 0.073). Thirty-and 90-day mortality was 3.3 and 8.7% in group 1 and 4.8 and 14.3% in group 2 (p = 0.617 and p = 0.242, respectively). Three-year overall survival was 54.6% in group 1 and 31.3% in group 2 (p = 0.03). Three-year cancer-specific survival was 64.8% in group 1 and 38.8% in group 2 (p = 0.037). Recurrence-free survival was 105 months in group 1 and 12 months in group 2 (p = 0.039). Conclusion: In light of increasing life expectancy in western nations, we sought to evaluate the impact of age in a large series of elderly patients undergoing RC for UCB. We found that RC offers acceptable perioperative complication rates in the oldest-old patient cohort (≥85 years). Therefore, RC for UCB can be offered as a viable treatment option even in the oldest patients.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Is It Safe to Offer Radical Cystectomy to Patients above 85 Years of Age? A Long-Term Follow-Up in a Single-Center Institution

et al. 2020

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“…Although, we cannot compare patients treated with chemotherapy with those not treated with chemotherapy since the tumor biology and prognosis are quite different, we saw no positive effect of the application of chemotherapy in the N0 patients, at least in our patient cohort. Recently, a study of muscle invasive BCa in Sweden showed that patients treated with radio/chemotherapy or radiotherapy had a better OS and DSS than untreated patients [47]. However, treated patients were not further stratified by their lymph node status.…”

Section: Discussionmentioning

confidence: 99%

CCL2 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Shows Divergent Prognostic Potential for Bladder Cancer Patients Depending on Lymph Node Stage

Eckstein

Epple

Jung

et al. 2020

Cancers

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Bladder cancer (BCa) is the ninth most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, markers for tumor cells and immune cells that are associated with prognosis are still needed. The chemokine CC motif ligand 2 (CCL2) could be such a marker. We analyzed the expression of CCL2 by immunohistochemistry (IHC) in 168 muscle invasive BCa samples using a tissue microarray. Application of a single cut-off for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; ≤6% of ICs vs. >6% of ICs) revealed 57 cases (33.9%) and 70 cases (41.7%) with CCL2-positive TCs or ICs, respectively. IHC results were correlated with clinicopathological and survival data. Positive CCL2 staining in TCs was associated with shorter overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) (p = 0.004, p = 0.036, and p = 0.047; log rank test) and appeared to be an independent prognostic factor for OS (RR = 1.70; p = 0.007; multivariate Cox’s regression analysis). In contrast, positive CCL2 staining in the ICs was associated with longer OS, DSS, and RFS (p = 0.032, p = 0.001, and p = 0.001; log rank test) and appeared to be an independent prognostic factor for DSS (RR = 1.77; p = 0.031; multivariate Cox’s regression analysis). Most interestingly, after separating the patients according to their lymph node status (N0 vs. N1+2), CCL2 staining in the ICs was differentially associated with prognosis. In the N0 group, CCL2 positivity in the ICs was a positive independent prognostic factor for OS (RR = 1.99; p = 0.014), DSS (RR = 3.17; p = 0.002), and RFS (RR = 3.10; p = 0.002), whereas in the N1+2 group, CCL2 positivity was a negative independent factor for OS (RR = 3.44; p = 0.019)) and RFS (RR = 4.47; p = 0.010; all multivariate Cox’s regression analyses). In summary, CCL2 positivity in TCs is a negative prognostic factor for OS, and CCL2 can mark ICs that are differentially associated with prognosis depending on the nodal stage of BCa patients. Therefore, CCL2 staining of TCs and ICs is suggested as a prognostic biomarker for BCa patients.

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“…Specifically in elderly patients, concerns have been expressed about the higher morbidity and mortality rates associated with RC [4], resulting in <20% of octogenarians with MIBC undergoing RC, which indicates that a significant number of patients are not currently being offered definitive treatment [5]. The evidence indicates that 85% of untreated patients with localized MIBC succumb to the disease within 5 years of the diagnosis, whereas <10% die from other causes [6]. At the same time, reported high-grade complication rates in elderly populations for open RC (ORC) have been up to 33%, and the 90-day mortality rates are approximately 15% [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Morbidity and mortality after robot‐assisted radical cystectomy with intracorporeal urinary diversion in octogenarians: results from the European Association of Urology Robotic Urology Section Scientific Working Group

et al. 2020

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To evaluate the postoperative complication and mortality rate following laparoscopic radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) in octogenarians. Patients and MethodsWe conducted a retrospective analysis comparing postoperative complication and mortality rates depending on age in a consecutive series of 1890 patients who underwent RARC with ICUD for bladder cancer between 2004 and 2018 in 10 European centres. Outcomes of patients aged <80 years and those aged ≥80 years were compared with regard to postoperative complications (Clavien-Dindo grading) and mortality rate. Cancer-specific mortality (CSM) and other-cause mortality (OCM) after surgery were calculated using the non-parametric Aalen-Johansen estimator. ResultsA total of 1726 patients aged <80 years and 164 aged ≥80 years were included in the analysis. The 30-and 90-day rate for high-grade (Clavien-Dindo grades III-V) complications were 15% and 21% for patients aged <80 years compared to 11% and 13% for patients aged ≥80 years (P = 0.2 and P = 0.03), respectively. In a multivariable logistic regression analysis adjusting for pre-and postoperative variables, age ≥80 years was not an independent predictor of high-grade complications (odds ratio 0.6, 95% confidence interval 0.3-1.1; P = 0.12). The non-cancer-related 90-day mortality was 2.3% for patients aged ≥80 years and 1.8% for those aged <80 years, respectively (P = 0.7). The estimated 12-month CSM and OCM rates for those aged <80 years were 8% and 3%, and for those aged ≥80 years, 15% and 8%, respectively (P = 0.009 and P < 0.001). ConclusionsThe minimally invasive approach to RARC with ICUD for bladder cancer in well-selected elderly patients (aged ≥80 years) achieved a tolerable high-grade complication rate; the 90-day postoperative mortality rate was driven by cancer progression and the non-cancer-related rate was equivalent to that of patients aged <80 years. However, an increased OCM rate in this elderly group after the first year should be taken into account. These results will support clinicians and patients when balancing cancer-related vs treatment-related risks and benefits.

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The natural history of untreated muscle‐invasive bladder cancer

Abstract: ConclusionsUntreated patients with MIBC are at very high risk of nearterm CSM. These findings may help balance the risks vs benefits of integrating curative intent therapy particularly in older patients with MIBC.

Cited by 84 publications

References 26 publications

Is It Safe to Offer Radical Cystectomy to Patients above 85 Years of Age? A Long-Term Follow-Up in a Single-Center Institution

Is It Safe to Offer Radical Cystectomy to Patients above 85 Years of Age? A Long-Term Follow-Up in a Single-Center Institution

CCL2 Expression in Tumor Cells and Tumor-Infiltrating Immune Cells Shows Divergent Prognostic Potential for Bladder Cancer Patients Depending on Lymph Node Stage

Morbidity and mortality after robot‐assisted radical cystectomy with intracorporeal urinary diversion in octogenarians: results from the European Association of Urology Robotic Urology Section Scientific Working Group

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