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Despite the lack of level 1 evidence, selective bladder-sparing therapy using trimodal therapy is currently recommended by guidelines as a standard of care in patients with non-metastatic, muscle-invasive bladder cancer who are eligible for the treatment. This article reviews major studies of selective, bladder-sparing therapy utilizing multiple modalities for muscle-invasive bladder cancer and those comparing the oncological outcomes between bladder-sparing therapy and radical cystectomy. Also discussed are predictive biomarkers potentially capable of guiding treatment decisions by patients with muscle-invasive bladder cancer and a novel strategy for boosting the antitumor immune response in bladder-sparing therapy. PubMed databases were searched for records of 30 June 2023 or earlier. Selective, bladder-sparing therapy appears to be underutilized at present. To promote its use, measures should be taken to facilitate the referral of eligible patients to specialist centers and broaden the number of facilities providing the therapy. Recent studies have suggested a prognostic benefit of radiotherapy for the primary lesion in patients with metastatic bladder cancer. Given that irradiation can induce the abscopal effect, particularly in combination with immune checkpoint inhibitors, demand for bladder-sparing therapies may increase in the context of treatments for metastases. [ABSTRACT FROM AUTHOR]

Objectives: To examine the clinical significance of the Vesical Imaging-Reporting and Data System (VI-RADS) in predicting outcome of multimodal treatment (MMT) in muscle-invasive bladder cancer (MIBC) patients. Methods: We reviewed 78 pathologically proven MIBC patients who underwent MMT including transurethral resection and chemoradiotherapy, followed by partial or radical cystectomy. Treatment response was assessed through histologic evaluation of cystectomy specimens. Two radiologists categorized the index lesions of pretherapeutic MRI according to the 5-point VI-RADS score. The associations of VI-RADS score with the therapeutic effect of MMT were analyzed. The diagnostic performance of VI-RADS scores with a cut-off VI-RADS scores ≤ 2 or ≤ 3 for predicting pathologic complete response to MMT (MMT-CR) was evaluated. Results: MMT-CR was achieved in 2 (100%) of VI-RADS score 1 (n = 2), 16 (84%) of score 2 (n = 19), 12 (86%) of score 3 (n = 14), 7 (64%) of score 4 (n = 11), and 14 (44%) of score 5 (n = 32). VI-RADS score was inversely associated with the incidence of MMT-CR (p = 0.00049). The cut-off VI-RADS score ≤ 2 and ≤ 3 could predict the favorable therapeutic outcome of MMT with high specificity (0.89 with 95% confidence interval [CI]: 0.71–0.98 and 0.82 with 95% CI: 0.62–0.94, respectively) and high positive predictive value (0.86 with 95% CI: 0.64–0.97 and 0.86 with 95% CI: 0.70–0.95, respectively). Conclusion: VI-RADS score may serve as an imaging marker in MIBC patients for predicting the therapeutic outcome of MMT. Clinical relevance statement: Muscle-invasive bladder cancer patients with a lower Vesical Imaging-Reporting and Data System score can be a good candidate for bladder-sparing treatment incorporating multimodal treatment. Key Points: • Vesical Imaging-Reporting and Data System (VI-RADS) score was potentially valuable for classifying pathologic tumor response in patients with muscle-invasive bladder cancer. • The likelihood of achieving complete response of multimodal treatment (MMT) decreased with increasing VI-RADS score. • VI-RADS score could serve as an imaging marker that optimizes patient selection for MMT. [ABSTRACT FROM AUTHOR]

Background: Several studies have investigated the potential role of the apparent diffusion coefficient (ADC) value of diffusion-weighted magnetic resonance imaging as a biomarker of high-grade and invasive bladder cancer. Methods: PubMed and the Cochrane Library were systematically searched in September 2021 to extract studies that evaluated the associations between ADC values, pathological T stage, and histological grade bladder cancers. The diagnostic performance of ADC values in detecting muscle-invasive bladder cancer (MIBC) and high-grade disease was systematically reviewed. Results: Six studies were included in this systematic review. MIBC showed significantly lower ADC values than non-muscle-invasive bladder cancer (NMIBC) in all six studies. The median (range) sensitivity, specificity, and area under the curve (AUC) of ADC values to detect MIBC among the four eligible studies were 73.5% (68.8–90.0%), 79.9% (66.7–84.4%), and 0.762 (0.730–0.884), respectively. Similarly, high-grade disease showed significantly lower ADC values than did low-grade disease in all four eligible studies. The median (range) sensitivity, specificity, and AUC of ADC values for detecting high-grade disease among the three eligible studies were 75.0% (73.0–76.5%), 95.8% (76.2–100%), and 0.902 (0.804–0.906), respectively. Conclusions: The ADC value is a non-invasive diagnostic biomarker for discriminating muscle-invasive and high-grade bladder cancer. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the oncological and functional outcomes associated with selective tetramodal bladder‐sparing therapy, comprising maximal transurethral resection of bladder tumour (TURBT), induction chemoradiotherapy (CRT), and consolidative partial cystectomy (PC) with pelvic lymph node dissection (PLND). Materials and Methods: In the present study, 154 patients with non‐metastatic muscle‐invasive bladder cancer (MIBC), prospectively enrolled in the tetramodal bladder‐preservation protocol, were analysed. After TURBT and induction CRT, patients showing complete remission were offered consolidative PC with PLND for the achievement of bladder preservation. Pathological response to induction CRT was evaluated using PC specimens. Oncological and functional outcomes after bladder preservation were evaluated using the following endpoints: MIBC‐recurrence‐free survival (RFS); cancer‐specific survival (CSS); overall survival (OS), and cross‐sectional assessments of preserved bladder function and quality of life (QoL) including uroflowmetry, bladder diary, International Prostate Symptom Score, Overactive Bladder Symptom Score and the 36‐item Short‐Form Health Survey (SF‐36) score. Results: The median follow‐up period was 48 months. Complete MIBC remission was achieved in 121 patients (79%) after CRT, and 107 patients (69%) completed the tetramodal bladder‐preservation protocol comprising consolidative PC with PLND. Pathological examination in these 107 patients revealed residual invasive cancer (≥pT1) that was surgically removed in 11 patients (10%) and lymph node metastases in two patients (2%). The 5‐year MIBC‐RFS, CSS and OS rates in the 107 patients who completed the protocol were 97%, 93% and 91%, respectively. As for preserved bladder function, the median maximum voided volume, post‐void residual urine volume, and nighttime frequency were 350 mL, 25 mL, and two voids, respectively. In the SF‐36, patients had favourable scores, equivalent to the age‐matched references in all the QoL scales. Conclusion: Selective tetramodal bladder‐preservation therapy, incorporating consolidative PC with PLND, yielded favourable oncological and functional outcomes in patients with MIBC. Consolidative PC may have contributed to the low rate of MIBC recurrence in patients treated according to this protocol. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes after radical cystectomy (RC) for bladder cancer.Methods: We reviewed the medical records of patients with urothelial bladder carcinoma who underwent RC with curative intent at seven hospitals between 1990 and 2013. After excluding patients with a history of upper urinary tract urothelial cancer or neoadjuvant chemotherapy, we analyzed 594 cases for the study. Preoperative estimated glomerular filtration rate (eGFR) was calculated using the three-variable Japanese equation for GFR estimation from serum creatinine level and age. Patients were divided into four groups of different CKD stages based on eGFR values (mL/min/1.73 m2), i.e., ≥ 60 (CKD stages G1–2), 45–60 (G3a), 30–45 (G3b), and < 30 (G4–5). Survival was estimated using the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards regression analyses addressed survivals after RC.Results: Median age of patients was 67 years. Patients were classified into CKD stages: G1–2 (n = 388; 65.3%), G3a (n = 122; 20.5%), G3b (n = 51; 8.6%), and G4–5 (n = 33; 5.6%). During a median follow-up of 4.0 years, 200 and 164 patients showed cancer progression and died of bladder cancer, with the 5-year progression-free survival (PFS) and cancer-specific survival (CSS) of 64.9 and 70.2%, respectively. On multivariate analyses, CKD stages of G3b or greater, advanced pT stage, lymph node metastasis, and positive lymphovascular invasion were independent poor prognostic factors for PFS and CSS.Conclusions: We demonstrated that the advanced preoperative CKD stage was significantly associated with poor oncological outcomes of the bladder cancer after RC. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC), the most common cancer arising from the human urinary tract, consists of two major clinicopathological phenotypes: muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). MIBC frequently metastasizes and is associated with an unfavorable prognosis. A certain proportion of patients with metastatic BC can achieve a remission with systemic chemotherapy; however, the disease relapses in most cases. Evidence suggests that MIBC comprises a small population of cancer stem cells (CSCs), which may be resistant to these treatments and may be able to form new tumors in the bladder or other organs. Therefore, the unambiguous identification of bladder CSCs and the development of targeted therapies are urgently needed. Nevertheless, it remains unclear where bladder CSCs originate and how they are generated. We review recent studies on bladder CSCs, specifically focusing on their proposed origin and the possible therapeutic options based on the CSC theory. [ABSTRACT FROM AUTHOR]

Diffusion-weighted magnetic resonance imaging is a type of functional imaging that is increasingly being applied in the management of upper tract urothelial carcinoma and bladder cancer. The image contrast is derived from differences in the Brownian motion of water molecules in tissues. The homogenous high signal intensity of upper tract urothelial carcinoma and bladder cancer on diffusion-weighted magnetic resonance imaging provides helpful diagnostic information for the presence of cancerous lesions in a non-invasive manner. Recently, growing evidence has emerged showing that diffusion-weighted magnetic resonance imaging can serve as an imaging biomarker for characterizing cancer pathophysiology, because the signal reflects biophysical information about the tissues. Quantitative analysis by evaluating the apparent diffusion coefficient values potentially reflects the histological grade and the biological aggressiveness of urothelial carcinoma. The apparent diffusion coefficient value could be a biomarker predicting the clinical course of upper tract urothelial carcinoma and bladder cancer. In addition, in chemoradiotherapy-based bladder-sparing approaches against muscle-invasive bladder cancer, the role of diffusion-weighted magnetic resonance imaging for predicting the chemoradiosensitivity and for monitoring therapeutic response has been shown. Diffusion-weighted magnetic resonance imaging is expected to improve the diagnostic accuracy, and this qualitative information might allow individualized treatment strategies for patients with urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Purpose To elucidate a role of apparent diffusion coefficient (ADC) value as a biomarker of bladder cancer, we investigated its associations with Ki-67 labeling index (LI) along with classical clinicopathological prognosticators. Materials and Methods Diffusion-weighted MRI (DW-MRI) at 1.5 Tesla using b-values of 0, 500, 1000, and 2000 s/mm2 was prospectively taken before transurethral resection by 132 bladder cancer patients. ADC value of index tumors was measured and compared with clinicopathological prognosticators including Ki-67 LI. Results ADC value was significantly lower in tumors with higher Ki-67 LIs, sessile tumors (versus papillary), larger tumors, higher grade disease, and higher T stage disease. ADC value inversely correlated with Ki-67 LI (ρ = −0.57; P < 0.0001). On multiple regression analysis, T stage and Ki-67 LI significantly correlated with ADC value. The Akaike information criterion confirms these two parameters constitute the best model for determining ADC value. Similarly, T stage and ADC value significantly correlated with Ki-67 LI and these two parameters composed the best model for predicting Ki-67 LI. Conclusion ADC value would reflect T stage and Ki-67 LI, representing invasive and proliferative potential, respectively. ADC value is likely to serve as a biomarker reflecting aggressiveness of bladder cancer. J. Magn. Reson. Imaging 2014;39:172-178. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

For metastatic bladder cancer patients, systemic cisplatin (CDDP)-based combination chemotherapy is the first-line choice of treatment. Although up to 70% of advanced bladder cancer patients initially show good tumor response to this form of combination chemotherapy, over 90% of good responders relapse and eventually die of the disease. According to the cancer stem cell theory, this phenomenon is attributable to the re-growth of bladder cancer-initiating cells (BCICs) that have survived chemotherapy. In this study, the authors have isolated BCICs from cultured human bladder cancer cells to analyze their sensitivity to CDDP and to investigate whether heat-shock protein 90 (Hsp90) inhibitors potentiate the cytotoxicity of CDDP on BCICs. First, the authors have confirmed that a CD44+ subpopulation of 5637 cells met the requirements to be considered tumor-initiating cells. These BCICs were more resistant to CDDP and exhibited more activity in the Akt and ERK oncogenic signaling pathways when compared with their CD44− counterparts. The Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), which simultaneously inactivated both Akt and ERK signaling at noncytocidal concentrations, synergistically potentiated the cytotoxicity of CDDP against BCICs by enhancing CDDP-induced apoptosis in vitro. The potentiating effect of 17-DMAG was more effective than a combination of the two inhibitors specific for the Akt and ERK pathways. Finally, the authors have confirmed that, though human BCIC xenografts exhibited resistance to a single administration of CDDP and the Hsp90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), 17-AAG sensitized them to CDDP in a mouse model. These data encourage clinical trials of Hsp90 inhibitors as they may improve therapeutic outcomes of CDDP-based combination chemotherapy against advanced bladder cancer. [ABSTRACT FROM AUTHOR]

Radical cystectomy plus urinary diversion, the reference standard treatment for muscle-invasive bladder cancer, associates with high complication rates and compromises quality of life as a result of long-term effects on urinary, gastrointestinal and sexual function, and changes in body image. As a society ages, the number of elderly patients unfit for radical cystectomy as a result of comorbidity will increase, and thus the demand for bladder-sparing approaches for muscle-invasive bladder cancer will also inevitably increase. Trimodality bladder-sparing approaches consisting of transurethral resection, chemotherapy and radiotherapy (Σ55-65 Gy) yield overall survival rates comparable with those of radical cystectomy series (50-70% at 5 years), while preserving the native bladder in 40-60% of muscle-invasive bladder cancer patients, contributing to an improvement in quality of life for such patients. Limitations of the trimodality therapy include (i) muscle-invasive bladder cancer recurrence in the preserved bladder, which most often arises in the original muscle-invasive bladder cancer site; (ii) potential lack of curative intervention for regional lymph nodes; and (iii) increased morbidity in the event of salvage radical cystectomy for remaining or recurrent disease as a result of high-dose pelvic irradiation. Consolidative partial cystectomy with pelvic lymph node dissection followed by induction chemoradiotherapy at lower dose (e.g. 40 Gy) is a rational strategy for overcoming such limitations by strengthening locoregional control and reducing radiation dosage. Molecular profiling of the tumor and functional imaging might play important roles in optimal patient selection for bladder preservation. Refinement of radiation techniques, intensified concurrent or adjuvant chemotherapy, and novel sensitizers, including molecular targeting agent, are also expected to improve outcomes and consequently provide more muscle-invasive bladder cancer patients with favorable quality of life. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? TURBT plus full-dose chemoradiotherapy (CRT) against MIBC allow more than 40% of patients to spare the bladder while maintaining survival outcomes comparable to those of radical cystectomy (RC) series, contributing to improvement of the patients' quality of life. Limitations of these protocols, however, include 1) MIBC recurrence in the preserved bladder mainly due to subclinical residual disease in the original MIBC site, 2) potential lack of curative intervention to regional lymph nodes and 3) increased mortality of salvage RC due to previous high-dose pelvic irradiation. We propose a novel selective bladder-sparing protocol consisting of induction low-dose CRT plus consolidative partial cystectomy with pelvic lymph node dissection, which potentially contributes to overcoming the limitations of the conventional bladder-sparing protocols. OBJECTIVE [ABSTRACT FROM AUTHOR]

Radical cystectomy for muscle-invasive bladder cancer (MIBC) patients frequently impairs their quality of life (QOL) due to urinary diversion. To improve their QOL, a bladder-sparing alternative strategy using chemoradiation has been developed. In bladder-sparing protocols, complete response (CR) to induction chemoradiation is a prerequisite for bladder preservation and favorable survival. Thus predicting chemoradiation resistance and overcoming it would increase individual MIBC patients' chances of bladder preservation. The aim of this study is to investigate putative molecular targets for treatment aimed at improving chemoradiation response. Expression levels of erbB2, NFκB, p53, and survivin were evaluated immunohistochemically in pretreatment biopsy samples from 35 MIBC patients in whom chemoradiation sensitivity had been pathologically evaluated in cystectomy specimens, and associations of these expression levels with chemoradiation sensitivity and cancer-specific survival (CSS) were investigated. Of the 35 patients, 11 (31%) achieved pathological CR, while tumors in the remaining 24 patients (69%) were chemoradiation-resistant. Multivariate analysis identified erbB2 and NFκB overexpression and hydronephrosis as significant and independent risk factors for chemoradiation resistance with respective relative risks of 11.8 (P = 0.014), 15.4 (P = 0.024) and 14.3 (P = 0.038). The chemoradiation resistance rate was 88.5% for tumors overexpressing erbB2 and/or NFκB, but only 11.1% for those negative for both (P <0.0001). The 5-year CSS rate was 74% overall. Through multivariate analysis, overexpression of erbB2 and/or NFκB was identified as an independent risk factor for bladder cancer death with marginal significance (hazard ratio 21.5, P = 0.056) along with chemoradiation resistance (P = 0.003) and hydronephrosis (P = 0.018). The 5-year CSS rate for the 11 patients achieving pathological CR was 100%, while that for the 24 with chemoradiation-resistant disease was 61% (P = 0.018). Thus, erbB2 and NFκB overexpression are relevant to chemoradiation resistance and are putative targets aimed at overcoming chemoradiation resistance in MIBC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DWI) in predicting therapeutic response to low-dose chemoradiotherapy (LCRT) against muscle-invasive bladder cancer (MIBC). Accurate assessment of response to induction therapy is an essential part of bladder-sparing therapeutic protocols against MIBC. However, conventional imaging studies are not useful in evaluating therapeutic response because of their inability to distinguish residual cancer from changes secondary to the treatment. Methods: Twenty patients with clinical T2-4aN0M0 bladder urothelial carcinoma (T2/T3/T4a: n = 10/8/2) who underwent induction LCRT comprising external beam radiotherapy to the bladder (40 Gy) concomitant with 2 cycles of cisplatin administration (20 mg/d for 5 days) followed by partial (n = 13) or radical cystectomy (n = 7) were prospectively enrolled. The patients underwent magnetic resonance imaging examinations with T2-weighted imaging (T2W), dynamic contrast-enhanced T1-weighted imaging (DCE), and DWI after LCRT. A finding of each protocol was compared with a pathologic finding of cystectomy specimen. Results: Pathologic examination of cystectomy specimens revealed pathologic complete response in 13 (65%) of the 20 patients. The sensitivity/specificity/accuracy of T2W, DCE, and DWI in predicting pathologic response was 43/45/44%, 57/18/33%, and 57/92/80%, respectively. Despite comparable sensitivity, DWI was significantly superior in specificity and accuracy to T2W (P = .03 and .02, respectively) and DCE (P = .002 for both). Conclusions: This is the first study to show the feasibility of DWI over T2W and DCE for assessing therapeutic response to induction chemoradiotherapy against MIBC. The high specificity of DWI indicates that DWI is useful to accurately predict pathologic complete response, allowing more optimal patient selection in bladder-sparing protocols. [Copyright &y& Elsevier]

OBJECTIVES To address the role of neoadjuvant concurrent chemo-radiotherapy (CRT) in muscle-invasive bladder cancer, by comparing retrospectively the oncological outcomes between a low-dose CRT (LCRT) plus partial cystectomy (PC) or radical cystectomy (RC) protocol and an immediate RC protocol. PATIENTS AND METHODS From 1997 to 2007, 119 patients with clinical stage T2–4aN0M0 bladder cancer received LCRT consisting of RT of 40 Gy in 4 weeks concurrently with two cycles of chemotherapy with cisplatin (20 mg/day for 5 days) during the first and fourth week of RT. Subsequently, 24 (20%) and 65 patients (55%) had PC and RC, respectively, while 30 (25%) had no curative surgery; the median follow-up was 36 months. From 1983 to 1997, 73 patients had an immediate RC; 29 (41%) received cisplatin-based adjuvant chemotherapy, and the median follow-up was 46 months. Oncological outcomes were compared retrospectively between these groups. RESULTS The cancer-specific survival (CSS) rate at 5 years was 75% and 61% for the LCRT protocol and immediate RC protocol, respectively ( P = 0.11). In patients with clinical stage T3N0M0 the LCRT protocol gave significantly better survival rates than the immediate RC protocol, with 5-year CSS rates of 62% vs 27% ( P = 0.006), while being comparable in those with clinical stage T2N0M0 disease (89% vs 88%, P = 0.84). In patients with clinical stage T3N0M0 the LCRT protocol provided a lower 5-year recurrence rate at distant sites than the immediate RC protocol (31% vs 62%, P = 0.09). CONCLUSIONS The LCRT plus PC or RC protocol gave significantly better survival rates than the historical, immediate RC protocol in patients with clinical stage T3N0M0 bladder cancer, suggesting that neoadjuvant CRT possibly has survival benefits for such patients. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical outcomes of patients with muscle-invasive bladder cancer treated with a prospective institutional protocol composed of induction low-dose chemoradiotherapy (LCRT) plus partial or radical cystectomy. Methods: From March 1997 to March 2006, 102 patients with Stage T2-T4aN0M0 bladder urothelial carcinoma consecutively underwent transurethral resection of the bladder tumor followed by LCRT consisting of radiotherapy to the bladder (radiation dose 40 Gy) concurrent with two cycles of intravenous (20 mg/d for 5 days) or intra-arterial (100 mg) cisplatin. Depending to their post-LCRT tumor status, patients were recommended to undergo partial or radical cystectomy with curative intent. Results: LCRT-related toxicity of grade 3 or greater was rare (3%). Of 97 eligible patients, 41 (42%) had a complete response, 29 (30%) a partial response, 24 (25%) had stable disease, and 3 (4%) progressive disease. Of the 97 patients, 19, underwent partial cystectomy, and 58 underwent radical cystectomy, 2 underwent transurethral resection of the bladder tumor, and 18 did not undergo surgery. The 5-year overall survival and cancer-specific survival (CSS) rate was 66% and 74%, respectively. The median follow-up was 43 months (range 3-126). On multivariate analysis, the response to LCRT had the strongest effect on CSS, and CSS was clearly stratified by the response to LCRT (P < .0001), with a 5-year CSS rate of 100% for the 41 patients with a complete response. Conclusions: The results of our study have shown that LCRT is an effective and less-toxic induction therapy against muscle-invasive bladder cancer. Our therapeutic protocol with LCRT plus partial or radical cystectomy yielded favorable survival outcomes. The response to LCRT was the strongest prognostic factor for CSS. [Copyright &y& Elsevier]

OBJECTIVE To investigate the effect of C-reactive protein (CRP) level on the prognosis of patients with muscle-invasive bladder cancer treated with chemoradiotherapy (ChRT), as it is increasingly recognized that the presence of a systemic inflammatory response is associated with poor survival in various malignancies. PATIENTS AND METHODS The clinical records of 88 patients with bladder urothelial carcinoma (cT2–4 N0M0) treated with ChRT were reviewed retrospectively. ChRT comprised external beam radiotherapy to the bladder (40 Gy) with two cycles of cisplatin (50–100 mg) at 3-week intervals. Elevated CRP was defined as >0.5 mg/dL. The survival rate was calculated using the Kaplan-Meier method, and a multivariate analysis was used to identify significant factors associated with prognosis, using a Cox proportional hazards model. RESULTS During the median (range) follow-up of 33 (3–117) months, 19 patients died from bladder cancer; the 5-year cancer-specific survival (CSS) rate was 73%. Ten patients had a high CRP level before ChRT (≥0.5 mg/dL) and their CSS rate was significantly worse than that in the remaining patients ( P = 0.003). Multivariate analysis showed that CRP and cT stage were independent prognostic indicators for CSS, with a hazard ratio of 1.80 (95% confidence interval 1.01–2.97; P = 0.046). Among 10 patients in those with elevated CRP the CRP levels became normal after ChRT in six, of whom all but one was alive with no evidence of recurrence or metastasis during the follow-up. By contrast, all four with no CRP normalization after ChRT died within 2 years. CONCLUSIONS To our knowledge this is the first study to report that elevation of CRP before treatment predicts a poor prognosis in patients with muscle-invasive bladder cancer who are receiving ChRT. Furthermore, failure of CRP levels to normalize after ChRT was associated with extremely poor survival. [ABSTRACT FROM AUTHOR]

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. In patients with cancer cachexia, anorexia, poor nutrition and systemic inflammation make the metabolic state more catabolic, resulting in sarcopenia. Thus, sarcopenia is considered as one of manifestations of cancer cachexia. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we summarized metabolic backgrounds of cancer cachexia and sarcopenia and definitions of sarcopenia based on computed tomography (CT) images. We conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients. Lastly, we discussed the impact of nutritional support, medication, and exercise on sarcopenia in cancer-bearing patients. [ABSTRACT FROM AUTHOR]

The author discusses the article "Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder," by R. P. Meijer and colleagues in the 2013 issue. He notes that the study has examined the use of sequential chemoradiotherapy and the development of limited disease small cell carcinoma (SCC) of the bladder. He cites that the recurrence of intravesical tumor has been observed outside the original tumor sites after sequential chemoradiotherapy.

Purpose We investigated whether the standardized apparent diffusion coefficient (ADC) value reflects bladder cancer characteristics across different centers. Methods Ninety-eight bladder cancer patients underwent MRI at two institutions. Standardized tumor ADC (sT-ADC) was calculated by dividing absolute tumor ADC (aT-ADC) by that of gluteus maximus. We compared ADCs between MRI protocols according to grade and T-stage. Results The differences in aT-ADC between MRI protocols were negated by sT-ADC. The best sT-ADC cut-offs to predict cancer aggressiveness in the development cohort worked in the validation cohort compared to the development cohort. Conclusion Standardized ADC overcomes the incompatibility between different MRI protocols. [ABSTRACT FROM AUTHOR]

Purpose: In chemoradiation (CRT)-based bladder-sparing approaches for muscle invasive bladder cancer (MIBC), patients who respond favorably to induction CRT enjoy the benefits of bladder preservation, whereas nonresponders do not. Thus, accurate prediction of CRT sensitivity would optimize patient selection for bladder-sparing protocols. Diffusion-weighted MRI (DW-MRI) is a functional imaging technique that quantifies the diffusion of water molecules in a noninvasive manner. We investigated whether DW-MRI predicts CRT sensitivity of MIBC. Methods and Materials: The study cohort consisted of 23 MIBC patients (cT2/T3 = 7/16) who underwent induction CRT consisting of radiotherapy to the small pelvis (40 Gy) with two cycles of cisplatin (20 mg/day for 5 days), followed by partial or radical cystectomy. All patients underwent DW-MRI before the initiation of treatment. Associations of apparent diffusion coefficient (ADC) values with CRT sensitivity were analyzed. The proliferative potential of MIBC was also assessed by analyzing the Ki-67 labeling index (LI) in pretherapeutic biopsy specimens. Results: Thirteen patients (57%) achieved pathologic complete response (pCR) to CRT. These CRT-sensitive MIBCs showed significantly lower ADC values (median, 0.63 × 10−3 mm2/s; range, 0.43–0.77) than CRT-resistant (no pCR) MIBCs (median, 0.84 × 10−3 mm2/s; range, 0.69–1.09; p = 0.0003). Multivariate analysis identified ADC value as the only significant and independent predictor of CRT sensitivity (p < 0.0001; odds ratio per 0.001 ×10−3 mm2/s increase, 1.03; 95% confidence interval, 1.01–1.08). With a cutoff ADC value at 0.74 × 10−3 mm2/s, sensitivity/specificity/accuracy in predicting CRT sensitivity was 92/90/91%. Ki-67 LI was significantly higher in CRT-sensitive MIBCs (p = 0.0005) and significantly and inversely correlated with ADC values (ρ = −0.67, p = 0.0007). Conclusions: DW-MRI is a potential biomarker for predicting CRT sensitivity in MIBC. DW-MRI may be useful to optimize patient selection for CRT-based bladder-sparing approaches. [Copyright &y& Elsevier]