The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis / 中华肿瘤杂志

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

Endoclips as novel fiducial markers in trimodality bladder-preserving therapy of muscle-invasive bladder carcinoma: feasibility and patient outcomes

ABSTRACT Hypothesis: Endoclip can be used as fiducial marker in urology. Objective: To assess the feasibility, cost effectiveness and reliability of endoclips as novel fiducial markers in precision radiotherapy, as part of a trimodality bladder-preserving treatment (TBPT) of muscle-invasive bladder carcinoma. Materials and Methods: This retrospective study was performed at Weifang People's Hospital (Weifang, China) from January 2015 to June 2018. A total of 15 patients underwent TBPT. Endoclips were applied to healthy edges of the resected bladder wall as novel fiducial markers. Radio-sensitizing chemotherapy and routine precision radiotherapy were given. The number and position of the endoclips during radiotherapy sessions were monitored. Complications and tumor recurrence were analyzed. Results: The mean age (±standard deviation) of the patients was 67±10 years (range 46-79). There were 3 females and 12 males. Forty-nine endoclips were applied in all patients (3.3±0.8). The tumor was completely visibly resected in all patients. The number of endoclips remained the same through the planned last radiotherapy session (3.3±0.8), i.e., none were lost. All endoclips were removed after the last radiotherapy session. The average number of follow-up months was 38.9±13.2 (range 11-52). There were no procedure-related complications at discharge or follow-up. At one-year, overall recurrence-free survival was 93.3%. Two patients had recurrences at 18 months and 10 months after TBPT, respectively, and salvage radical cystectomy was performed with no further recurrences. Another patient died due to metastasis 9 months after the completion of therapy. Conclusions: Endoclips are reliable, safe and cost-effective as novel fiducial markers in precision-radiotherapy post-TBPT.

Individual control of urine volume to improve stability of bladder volume in radiotherapy of urinary tumor / 北京大学学报(医学版)

OBJECTIVE@#To explore the training mode of individual urine volume control, to take indi-vidual expected urine volume as the goal of bladder control in patients with urinary system tumors, and to improve the accuracy of bladder control during radiotherapy by active training of bladder receptivity.@*METHODS@#Twenty-five patients of urinary system tumors were enrolled from May 2019 to September 2019, of whom, 21 patients had prostate cancer, and 4 had bladder cancer. Training of bladder filling started before CT simulation. The patients were required to take the individual bladder filling as the training goal, and the optimal bladder volume range was suggested to be 200－400 mL. After 2－4 weeks of training, the prescribed volume of the bladder was determined according to the patient's bladder receptivity. The volume of the bladder was measured by images of plain CT and images 8-minutes after intravenous contrast injection. The patient's bladder volume was measured using BladderScan before treatment. CBCT (Cone-beam CT) was performed, and bladder volume was measured before treatment. The bladder volume was measured again using BladderScan after treatment.@*RESULTS@#The mean bladder volume of simulation (VCT01) was (262±130) mL, ranging from 78 mL to 505 mL. The mean self-evaluation bladder volume before radiotherapy (VEVA01) was (238±107) mL, ranging from 100 mL to 400 mL. The mean BladderScan measured volume before radiotherapy (VBVI01) was (253±123) mL, ranging from 60 mL to 476 mL. The mean cone-beam CT measured volume before radiotherapy (VCBCT) was (270±120) mL, ranging from 104 mL to 513 mL. There was a correlation between VEVA01 and VBVI01, VCT01 and VBVI01, VCT01, and VBVI01, and there was no significant difference in paired t-test. There was a correlation between differences of self-evaluation bladder volume before radiotherapy(VEVA01) and simulation CT (VCT01) and differences of self-evaluation bladder volume before radiotherapy (VEVA01) and cone-beam CT (VCBCT), and there was no significant difference in paired samples by t-test.@*CONCLUSION@#During radiotherapy for urinary system tumors, such as prostate cancer and bladder cancer, with the assistance of BladderScan, the patients could try to hold their urine moderately according to their conditions, and individualized bladder prescription may be beneficial to achieve stable bladder volume during radiotherapy.

Small cell bladder cancer: should we consider prophylactic cranial irradiation?

ABSTRACT Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.

Lipiodol as a Fiducial Marker for Image-Guided Radiation Therapy for Bladder Cancer

Purpose To evaluate Lipiodol as a liquid, radio-opaque fiducial marker for image-guided radiation therapy (IGRT) for bladder cancer.Materials and Methods Between 2011 and 2012, 5 clinical T2a-T3b N0 M0 stage II-III bladder cancer patients were treated with maximal transurethral resection of a bladder tumor (TURBT) and image-guided radiation therapy (IGRT) to 64.8 Gy in 36 fractions ± concurrent weekly cisplatin-based or gemcitabine chemotherapy. Ten to 15mL Lipiodol, using 0.5mL per injection, was injected into bladder submucosa circumferentially around the entire periphery of the tumor bed immediately following maximal TURBT. The authors looked at inter-observer variability regarding the size and location of the tumor bed (CTVboost) on computed tomography scans with versus without Lipiodol.Results Median follow-up was 18 months. Lipiodol was visible on every orthogonal two-dimensional kV portal image throughout the entire, 7-week course of IGRT. There was a trend towards improved inter-observer agreement on the CTVboost with Lipiodol (p = 0.06). In 2 of 5 patients, the tumor bed based upon Lipiodol extended outside a planning target volume that would have been treated with a radiation boost based upon a cystoscopy report and an enhanced computed tomography (CT) scan for staging. There was no toxicity attributable to Lipiodol.Conclusions Lipiodol constitutes a safe and effective fiducial marker that an urologist can use to demarcate a tumor bed immediately following maximal TURBT. Lipiodol decreases inter-observer variability in the definition of the extent and location of a tumor bed on a treatment planning CT scan for a radiation boost.

The efficacy of hemostatic radiotherapy for bladder cancer-related hematuria in patients unfit for surgery

Objective The aim of our study was to assess short and mid-term clinical efficacy of external beam radiation therapy to achieve hemostasis in patients with bladder-cancer related gross hematuria who were unfit for surgery. We also assessed hypofractionation as a possible alternative option for more severe patients. Patients and Methods Thirty-two patients were included for hemostatic radiation therapy, with two schedules based on Eastern Cooperative Oncology Group performance status. The standard treatment was 30 Gy in 10 fractions over 2 weeks. More severe patients underwent a hypofractionated regimen, with 20 Gy in 5 fractions over a one week period. Clinical evaluation was performed at 2 weeks and 6 months. Results At 2 weeks, 69% of patients were hematuria-free. Subgroup analysis showed that 79% of patients undergoing hypofractionated regimen were hematuria-free. A total of 54% were hematuria-free with the standard regimen. Based on tumor stage, hematuria was controlled at 2 weeks for 57% of non-muscle invasive tumors and 72% of muscle-invasive tumors. After 6 months, 69% of patients had relapsed, regardless of tumor stage or therapy schedules. Conclusions Hemostatic radiotherapy is an effective option for palliative-care hematuria related to bladder cancer in patients unfit for surgery. Although it appears to be rapidly effective, its effect is of limited duration. Hypofractionation also seems to be an effective option; however larger cohorts and prospective trials are needed to evaluate its efficacy compared to standard schedules. .

Evaluation of Acute Toxicity and Symptoms Palliation in a Hypofractionated Weekly Schedule of External Radiotherapy for Elderly Patients with Muscular Invasive Bladder Cancer

Aim To evaluate acute toxicity and symptoms palliation of a weekly hypofractionated 3DCRT schedule as radical treatment in elderly patients with organ confined bladder cancer cT1-2N0. Materials and Methods Between February 2005 and June 2011, 58 prospectively selected patients diagnosed with organ confined bladder cancer were treated with external 3DCRT (4-field arrangement). All candidates were medically inoperable, with poor performance status, and with age ranged from 75 to 88 years (median 78). A dose of 36 Gy in 6 weekly fractions was prescribed. The primary study endpoints were the evaluation of haematuria, dysuria, frequency and pain palliation as well as the acute toxicity according to the RTOG/EORTC scale: an assessment was performed at baseline, during and 3 months after radiotherapy, while the maximum reported score was taken into account. Results The gastrointestinal acute toxicities were 13/58 (22.4%) and 5/58 (5.6%), for grade I and II respectively. The genitourinary acute toxicities were 19/58 (32.7%) and 10/58 (17.2%), for grade I and II respectively. In terms of clinical outcome, 55/58 patients (94.8%) reported palliation of haematuria, while 19 out of 58 reported no change in frequency and dysuria. All patients reported significant improvement (P < 0.01) for pain, concerning the visual analogue score before and after radiotherapy. The median progression free survival was 14 months. CONCLUSIONS The incidence of patient-reported acute toxicity following weekly hypofractionated external 3DCRT is low while the symptom palliation compares very favorably with other reported outcomes. .

The role of radiotherapy in urinary bladder cancer: current status

The role of radiotherapy (RT) in the treatment of urinary bladder cancer has undergone several modifications along the last decades. In the beginning, definitive RT was used as treatment in an attempt to preserve the urinary bladder; however, the results were poor compared to those of radical surgery. Recently, many protocols have been developed supporting the use of multi-modality therapy, and the concept of organ preservation began to be reconsidered. Although phase III randomized clinical studies comparing radical cystectomy with bladder preservation therapies do not exist, the conservative treatment may present low toxicity and high indexes of complete response for selected patients. The aim of this study was to review the literature on the subject in order to situate RT in the current treatment of urinary bladder cancer.

Invasive bladder cancer: the role of bladder preserving therapy

To evaluate the reported outcomes of multimodality therapy with organ preservation in invasive bladder cancer and assess it as an alternative for radical cystectomy in selected cases. All the articles on multimodality therapy with organ preservation in invasive bladder cancer, published from 1974 to 2004, were reviewed and the results were compared with the outcome of radical cystectomy in cases with invasive bladder cancer. Multimodality therapy is transurethral resection of the bladder tumor [TURBT] combined with chemoradiation therapy. It yields a 36% to 48% 5-year survival rate, when the bladder is preserved, and an overall rate of 48% to 63%. This method takes a long time for treatment and is accompanied by significant morbidity and mortality. Cystectomy will be required in 34% to 45% of the patients, during the treatment course, and in 28%, repeat TURBT will be performed due to recurrence of superficial tumors. Organ preserving in multimodality therapy of invasive bladder cancer can have acceptable results in some special situation, provided that a close cooperation between urologist, radiotherapist, and oncologist exists. However, radical cystectomy is still considered the standard treatment for invasive bladder cancer

Impact of gemcitabine and cisplatin with radiotherapy in locally advanced or metastatic transitional cell carcinoma of urinary bladder

The primary object of this study is to evaluate the efficacy and safety of Gemcitabine and Cisplatin along with radiotherapy in transitional cell carcinoma of urinary bladder. Patients and Twenty patients with locally advanced or metastatic TCC of urinary bladder were enrolled during the 22-months period from January, 1999 to October, 2000 and followed up till March 2002.Three patients received 4 cycles, five patients received 5 cycles and twelve patients received 6 cycles of Gemcitabine 1250mg / m2 on day 1 and day 8 and Cisplatin 80mg / m2 on day 1; administered every 3 weeks. No patient received prior chemotherapy, radiotherapy or surgery. However, four patients received prior intravesical chemotherapy. All patients received radiotherapy after completion of chemotherapy regimen. Nineteen patients achieved complete response at the end of the treatment. The complete response rate was 95%. The confidence interval was at 95%, level of confidence ranged from 85% to 100%. Median duration of clinical benefit was 21 months. Six patients [30%] were documented neutropenia, three patients [15%] documented thrombocytopenia. No life threatening toxicity was observed. Gemcitabine and Cisplatin along with radiotherapy in locally or metastatic Transitional cell carcinoma of urinary bladder, exhibited pronounced response rate among all the patients. The toxicity profile remained extremely low and disease free survival enhanced. The above investigation may further be continued at a larger scale encompassing a wide band of subjects

Carcinoma de vejiga tratado con radioterapia y sus posibles complicaciones: informe de un caso y revisión de la literatura / Urinary bladder carcinoma treated with radiotherapy and its possible complications: case report and review of the literature

La fístula enterovesical es una complicación conocida, secundaria al manejo con radioterapia externa en casos de carcinoma de vejiga. Se informa el caso de un paciente de 80 años de edad con diagnóstico de carcinoma de células transicionales de vejiga de tipo infiltrativo, tratado con radioterapia. Un año después de este tratamiento presenta doble fístula enterovesical secundaria a proctitis e ileítis postradiación que se resuelve por medio de procedimiento quirúrgico

Estudo do DNA na previsäo de resposta à quimioterapia por M-VAC em câncer infiltrativo de bexiga / DNA ploidy as a possible predictor of response to M-VAC chemotherapy for locally invasive bladder cancer

Em 20 pacientes com CCTB localmente infiltrativo realizou-se pesquisa do conteúdo do DNA em amostras de tumores obtidos por ressecçäo ou biópsia endoscópica, para avaliar a possibilidade de previsäo de resposta àquimioterapia por M-VAC. Histologicamente, 30 por cento dos tumores eram diferenciados e 70 por cento pouco diferenciados. Os tumores eram diplóides em 5 por cento, tetraplóides em 5 por cento e aneuplóide em 90 por cento. Observou-se resposta completa à quimioterapia em 55 por cento e resposta negativa em 45 por cento dos casos. A avaliaçäo da haploidia do DNA näo contribuiu para a detecçäo de neoplasias responsivas ao esquema M-VAC

Carcinom Bladder: a study of 44 cases

Over a period of six year, 44 cases of bladder carcinoma were admitted in Surgical Unit IV of Civil Hospital, Karachi. Of these 31[70.45%] belonged to be transitional cell type, 9[20.45%] were anaplastic and 2[4.55%] squamous cell carcinoma, while two were secondary carcinoma. Majority [68.18%] of cases were seen between 40 to 60 years of age with a male of female ratio of about 3:1. Lateral wall of the bladder was the most common site [50%] followed by posterior wall [18.18%] and anterior wall [13.64%]. Cystoscopy and transurethral resection were the main for diagnosis and treatment, while radiotherapy and chemotherapy were less frequently used

Preoperative chemotherapy in T2-T3, Nx, Mo bladder cancer: protocol modification and early experience

A prospective randomized study of preoperative chemotherapy for transitional cell bladder cancer was carried out. Patients were randomized either to preoperative chemotherapy then cystectomy [arm I], or cystectomy alone [arm II]. All patients in arm I received 2 cycles of the combination therapy of PMV: Paraplatin [300 mg/m2 IV, day 1, Methotrexate [50 mg/m2 IV, days 1 and 14] and Vinblastine [4 mg/m2 IV, days 1 and 14]. Until now, 35 patients were entered in arm I and 44 in arm II. From the preliminary results, it was concluded that preoperative chemotherapy protocol PMV is safe, well tolerated and effective. It can be given as outpatient treatment with minimal toxicity. The two years actuarial disease free survival is 70% for arm I and 46% for arm II with P value of 0.1. More patients and prolonged follow up were needed to detect the impact disease free and over all patients survival

Effect of gamma radiation therapy on microorganisms causing secondary infection in patients with cancer bladder

Urinary tract infection in cancer patients is of major importance not only because it is of common occurrence but also because it may be the source of blood invasion by bacteria or their products. In this study, 130 midstream urine samples collected from patients with cancer bladder were cultured on different media. All isolated bacteria and yeast were identified systematically and than subjected to these investigations: Sensitivity to increasing doses of gamma radiation, sensitivity to different antimicrobial agents and measurement of DNA content by cytophotometry. Bacteria and yeast were isolated from urine in 73 cases [56.15%] of all cases [130]. E. coli was isolated in 31.4%, Pseudomonas aeroginosa in 21.9%, Proteus in 12.3%, Staph. aureus in 18.2% and Candida in 4.1%. Pseudomonas was the most sensitive organism to gamma radiation D10 [0.06 KGy] followed by E. coli D10 [0.35 KGy] then Staph. D10 [0.36 KGy] while Candida was the most radio resistant D10 [1.11 KGy]. All tested organisms had higher DNA content after exposure to therapeutic dose of radiation than before radiation. These changes in DNA content lead to changes in the sensitivity of organism to different antibiotics, sublethal doses of radiation cause an increase in spontaneous emergency of resistant mutants. Changes in DNA content and antibiotic sensitivity were statistically significant

Protocolo para tratamento do carcinoma invasivo da bexiga / Therapeutic protocol for treatment of urinary bladder invasive carcinoma

O protocolo aqui apresentado e usado no nosso Departamento é uma consequência dos atuais conhecimentos etiopatogênicos da doença. Baseia-se nos seguintes parâmetros: anaplasia celular, infiltraçäo da parede vesical, metástase loco-regional e à distância. No pré-operatório usou-se a quimioterapia sistêmica com M-VAC ou radioterapia externa. Conforme resposta obtida será indicada a cistectomia parcial ou radical, ambas com linfadenectomia pélvica.

Câncer de bexiga / Bladder cancer

Doença que tem sua maior incidência na 6ª e 7ª décadas de vida, o câncer de bexiga é considerado doença profissional em alguns países, devido ao contato do paciente com certas substâncias no ambiente de trabalho. A variaçäo da incidência em áreas geográficas diferentes tem sido atribuída a vários carcinógenos industriais e ambientais. E é sobre esses agentes e substâncias químicas que o presente trabalho discorre, elucidando ainda os leitores sobre o diagnóstico e forma de tratamento