Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03.

1998 ◽  
Vol 16 (11) ◽  
pp. 3576-3583 ◽  
Author(s):  
W U Shipley ◽  
K A Winter ◽  
D S Kaufman ◽  
W R Lee ◽  
N M Heney ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Radiation Therapy ◽  
Survival Rate ◽  
Neoadjuvant Chemotherapy ◽  
Clinical Stage ◽  
Radiation Therapy Oncology Group ◽  
Distant Metastases ◽  
Phase Iii ◽  
Bladder Preservation

PURPOSE To assess the efficacy of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy in patients with muscle-invading bladder cancer treated with selective bladder preservation. PATIENTS AND METHODS One hundred twenty-three eligible patients with tumor, node, metastasis system clinical stage T2 to T4aNXMO bladder cancer were randomized to receive (arm 1, n=61 ) two cycles of MCV before 39.6-Gy pelvic irradiation with concurrent cisplatin 100 mg/m2 for two courses 3 weeks apart. Patients assigned to arm 2 (n=62) did not receive MCV before concurrent cisplatin and radiation therapy. Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. The CR patients were treated with an additional 25.2 Gy to a total of 64.8 Gy and one additional dose of cisplatin. Those with less than a CR underwent cystectomy. The median follow-up of all patients who survived is 60 months. RESULTS Seventy-four percent of the patients completed the protocol with, at most, minor deviations; 67% on arm 1 and 81% on arm 2. The actuarial 5-year overall survival rate was 49%; 48% in arm 1 and 49% in arm 2. Thirty-five percent of the patients had evidence of distant metastases at 5 years; 33% in arm 1 and 39% in arm 2. The 5-year survival rate with a functioning bladder was 38%, 36% in arm 1 and 40% in arm 2. None of these differences are statistically significant. CONCLUSION Two cycles of MCV neoadjuvant chemotherapy were not shown to increase the rate of CR over that achieved with our standard induction therapy or to increase freedom from metastatic disease. There was no impact on 5-year overall survival.

Bladder preservation by combined modality therapy for invasive bladder cancer.

1997 ◽  
Vol 15 (3) ◽  
pp. 1022-1029 ◽  
Author(s):  
L A Kachnic ◽  
D S Kaufman ◽  
N M Heney ◽  
A F Althausen ◽  
P P Griffin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Survival Rate ◽  
Combined Modality Therapy ◽  
Clinical Stage ◽  
Survival Rates ◽  
Overall Survival Rate ◽  
Bladder Preservation ◽  
Combined Modality ◽  
Long Term Survivors

PURPOSE To update the efficacy of a selective multimodality bladder-preserving approach by transurethral resection (TURBT), systemic chemotherapy, and radiation therapy. PATIENTS AND METHODS From 1986 through 1993, 106 patients with muscle-invading clinical stage T2 to T4a,Nx,M0 bladder cancer were treated with induction by maximal TURBT and two cycles of chemotherapy (methotrexate, cisplatin, vinblastine [MCV]) followed by 39.6-Gy pelvic irradiation with concomitant cisplatin. Patients with a negative postinduction therapy tumor site biopsy and cytology (a T0 response, 70 patients) plus those with less than a T0 response but medically unfit for cystectomy (six patients), received consolidative chemoradiation to a total of 64.8 Gy. Surgical candidates with less than a T0 response (13 patients) and patients who could not tolerate the chemoradiation (six patients) went to immediate cystectomy. The median follow-up duration is 4.4 years. RESULTS The 5-year actuarial overall survival and disease-specific survival rates of all patients are 52% and 60%, respectively. For clinical stage T2 patients, the actuarial overall survival rate is 63%, and for T3-4, 45%. Thirty-six patients (34%) underwent cystectomy, all with evidence of tumor activity, including 17 with an invasive recurrence. The 5-year overall survival rate with an intact functioning bladder is 43%. Among 76 patients who completed bladder-preserving therapy, the 5-year rate of freedom from an invasive bladder relapse is 79%. No patient required cystectomy for treatment-related bladder morbidity. CONCLUSION Combined modality therapy with TURBT, chemotherapy, radiation, and selection for organ-conservation by response has a 52% overall survival rate. This result is similar to cystectomy-based studies for patients of similar age and clinical stages. The majority of the long-term survivors retain fully functional bladders.

Recurrence pattern after neoadjuvant chemotherapy compared to surgery alone in patients with muscle-invasive bladder cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 374-374
Author(s):  
Takuya Koie ◽  
Chikara Ohyama ◽  
Atsushi Imai ◽  
Shingo Hatakeyama ◽  
Takahiro Yoneyama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Lymph Node ◽  
Survival Rate ◽  
Neoadjuvant Chemotherapy ◽  
Propensity Score ◽  
Distant Metastases ◽  
Invasive Bladder Cancer ◽  
Recurrence Pattern ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

374 Background: Neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC) has better survival benefit than radical cystectomy (RC) alone. However, recurrences still occur in many cases and recurrent disease is the most lethal factor associated with death in MIBC. On the other hand, the rate and pattern of recurrences after neoadjuvant chemotherapy in MIBC patients remains unclear. Methods: Eligible patients had histologically confirmed stage T2-T4a muscle-invasive urothelial carcinoma of the bladder without lymph node or distant metastasis in this study. The cohort of neoadjuvant group consists of 130 patients with MIBC. The cohort of RC alone group includes 135 patients with MIBC treated with RC and bilateral pelvic lymph node dissection between May 1994 and July 2007. Propensity score matching was used to adjust for potential selection biases associated with treatment type. Recurrence site was defined as local, LN (lymph nodes), and distant metastases. Results: Propensity score-matched analysis indicated 130 matched pairs from both groups. The 5-year overall survival rate was 91% for neoadjuvant GCarbo versus 49% for RC alone group (P < 0.0001). The disease-free survival rate was 87% for neoadjuvant GCarbo versus 57% for surgery alone (P < 0.0001). The distant metastases were comparable in both groups. The total number of local recurrences or LN mets was markedly decreased in neoadjuvant GCarbo compared with RC alone cohort. Conclusions: The MIBC patients treated with neoadjuvant GCarbo achieved an improved oncological outcome with a different recurrence pattern compared to RC alone.

A phase III randomized study of neoadjuvant chemotherapy (NAC) alone or in combination with nivolumab (NIVO) ± linrodostat mesylate, followed by adjuvant postsurgical NIVO ± linrodostat, in cisplatin-eligible muscle invasive bladder cancer (MIBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5091-TPS5091
Author(s):  
Guru Sonpavde ◽  
Andrea Necchi ◽  
Shilpa Gupta ◽  
Gary D. Steinberg ◽  
Juergen Gschwend ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Clinical Stage ◽  
Randomized Study ◽  
Pathologic Complete Response ◽  
Phase Iii ◽  
Clinical Activity ◽  
Bladder Tissue ◽  
Normal Bladder ◽  
Muscle Invasive

TPS5091 Background: Immuno-oncology (IO) therapies have revolutionized the treatment (tx) of pts with advanced bladder cancer (advBC). For pts with cisplatin-eligible, muscle invasive BC (MIBC), the recommended tx is cisplatin-based neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC). However, since only ≈ 30% of pts achieve a pathologic complete response (pCR) translating to improved long-term outcomes with approved regimens, new therapies are needed. PD-L1 expression is associated with aggressive BC and has been shown to increase in BC after NAC, supporting the therapeutic pursuit of the PD-1/PD-L1 axis. Additionally, expression of indoleamine 2,3-dioxygenase (IDO) is higher in BC than in normal bladder tissue and is associated with advanced disease and poor clinical outcome. Linrodostat mesylate, a selective, potent, once-daily oral IDO1 inhibitor that works to reduce kynurenine production, has demonstrated clinical activity in combination with NIVO (anti–PD-1) in pts with IO tx–naive advBC who had ≥ 1 prior line of therapy (ORR, 37%). Taken together, these data provide a rationale for investigating NAC + NIVO + linrodostat in MIBC. Here we describe a randomized, partially blinded, phase 3 study evaluating the efficacy and safety of NAC ± NIVO ± linrodostat followed by RC and continued IO tx in pts with MIBC (NCT03661320). Methods: Pts aged ≥ 18 years with previously untreated MIBC (clinical stage T2-T4a, N0, M0), creatinine clearance ≥ 50 mL/min, and predominant UC histology who are eligible for cisplatin-based NAC and RC will be enrolled. Pts with evidence of positive lymph node; metastatic BC; or prior systemic therapy, radiotherapy, or surgery for BC other than TURBT are not eligible. Pts will be randomized to receive NAC (gemcitabine/cisplatin; arm A), NAC + NIVO + oral placebo (arm B), or NAC + NIVO + linrodostat (arm C) followed by RC (all arms); arms B and C will receive continued IO tx. Primary endpoints include pCR after neoadjuvant tx and event-free survival (arms C vs A; arms B vs A). Secondary endpoints are overall survival and safety. This global study in 28 countries began accrual in Nov 2018 and has a target enrollment of 1200 pts. Clinical trial information: NCT03661320 .

Significance of prophylactic urethrectomy at the time of radical cystectomy for bladder cancer

2020 ◽  
Author(s):  
Kyohei Hakozaki ◽  
Eiji Kikuchi ◽  
Koichiro Ogihara ◽  
Keisuke Shigeta ◽  
Takayuki Abe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Survival Rate ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Carcinoma In Situ ◽  
Bladder Tumour ◽  
Overall Survival Rate ◽  
Definitive Evidence

Abstract Background Prophylactic urethrectomy at the time of radical cystectomy is frequently recommended for patients with bladder cancer at a high risk of urethral recurrence without definitive evidence. The present study attempted to clarify the survival benefits of performing prophylactic urethrectomy. Methods We identified 214 male patients who were treated by radical cystectomy with an incontinent urinary diversion in our seven institutions between 2004 and 2017. We used propensity score matching and ultimately identified 114 patients, 57 of whom underwent prophylactic urethrectomy (prophylactic urethrectomy group) and 57 who did not (non-prophylactic urethrectomy group). Results No significant differences were observed in the 5-year overall survival rate between the prophylactic urethrectomy and non-prophylactic urethrectomy groups in the overall. However, the local recurrence rate was significantly lower in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.015). In the subgroup of 58 patients with multiple tumours and/or concomitant carcinoma in situ at the time of transurethral resection of bladder tumour, the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.021). A multivariate analysis revealed that performing prophylactic urethrectomy was the only independent predictor of the overall survival rate (P = 0.016). In those patients who were treated without neoadjuvant chemotherapy (n = 38), the 5-year overall survival rate was significantly higher in the prophylactic urethrectomy group than in the non-prophylactic urethrectomy group (P = 0.007). Conclusions Prophylactic urethrectomy at the time of radical cystectomy may have a survival benefit in patients with multiple tumours and/or concomitant carcinoma in situ, particularly those who do not receive neoadjuvant chemotherapy.

scholarly journals Background variables for the patients with invasive bladder cancer suitable for bladder-preserving therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15610-15610
Author(s):  
N. Miyanaga ◽  
H. Akaza ◽  
S. Hinotsu ◽  
A. Joraku ◽  
T. Oikawa ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Survival Rate ◽  
Tumor Size ◽  
Univariate Analysis ◽  
Complete Response ◽  
Overall Survival Rate ◽  
Bladder Preservation ◽  
Cause Specific Survival

15610 Background: The present study was undertaken to identify the patients suitable for bladder preservation by analysis of our previous studies. Methods: The subjects of this study were all 72 patients with T2–3N0M0 bladder cancer who underwent bladder- preserving therapy in our institute. The therapy involved intra-arterial chemotherapy with MTX and CDDP and concomitant radiotherapy. Results: Of the evaluable 70 cases, complete response was confirmed in 57 cases (81.4%). The median follow-up was 45.3 months. The 5-year cause-specific survival rate was 81 % and the 5-year overall survival rate was 66%. Based on the results of univariate analysis, variables contributing to complete response were selected. In T2 cases, tumor size of 3 cm or less was scored 0 and tumor larger than 3 cm was scored 1, while single tumor was scored 0 and multiple tumors were scored 1. In T3 cases, tumor size of 3 cm or less was scored 0 and tumor larger than 3 cm was scored 1, while G2 was scored 0 and G3 scored 1. The CR rates were 93.8% and 92.6% for total scores of 0 and 1, respectively, and 62.9% for a total score of 2 (P = 0.003; score 0 or 1 vs 2). The overall survival rate was significantly higher in the former group (P = 0.003). Conclusion: Bladder-preserving therapy can be acceptable for cases of single T2N0M0 tumor with a size of =3 cm and for T3N0M0 cases with a tumor size of =3 cm. No significant financial relationships to disclose.

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