Bladder-sparing multimodality treatment of muscle-invasive bladder cancer: A five-year follow-up

doi:10.1016/S0090-4295(99)80262-3

Urology

Volume 46, Issue 4, October 1995, Pages 499-505

https://doi.org/10.1016/S0090-4295(99)80262-3 Get rights and content

Abstract

Objectives

To determine the long-term results of a bladder-sparing approach in the treatment of muscle-invasive bladder cancer.

Methods

Ninety-four patients with invasive transitional cell carcinoma of the bladder were treated by transurethral resection followed by 2 or 3 cycles of cisplatin-based chemotherapy. Patients were then treated with 6480 cGy of radiation in 49 patients, segmental cystectomy in 8, or surveillance only in 7. Patients who failed to respond to chemotherapy or radiation therapy, or who developed recurrent muscle-invasive disease in follow-up, underwent salvage cystectomy. Patients were then carefully followed for a median follow-up of more than 5 years.

Results

After initial therapy, 53 patients (56%) were alive with their bladder preserved. Thirty of those 53 (57%) developed a local recurrence in follow-up. After a median follow-up of more than 5 years, the ultimate relapse-free survival is 49% (Stage T2, 84%; T3, 53%; and T4, 11 %; P < 0.01). Of all patients enrolled, 53% had bladder preservation; however, of the currently surviving patients, 16 of 39 (41 %) have their bladders intact (T2, 50%; T3, 37%; T4, 0%). Only 18% of the initially enrolled population is alive with a preserved bladder. The 5-year survival of patients who had cystectomy at some point during the study, compared with those who have had their bladders preserved, was 65% versus 40%, respectively (P <0.01).

Conclusions

Our long-term results with multimodality therapy with attempted bladder preservation showed no definitive improvement in survival compared with modem series of cystectomy alone, and a disappointingly low rate of disease-free bladder preservation. We found a high rate of locally recurrent disease in the preserved bladders. We also noted a decrease in survival in our patients with bladder preservation compared with those without preservation. Bladder preservation, although possible, should be limited to a very select group of patients.

References (9)

TesterW et al.
Combined modality program with possible organ preservation for invasive bladder carcinoma: results of RTOG protocol 85-12
Int J Radiat Oncol Biol Phys
(1993)
HerrHW et al.
Baccillus Calmette-Guérin therapy for superficial bladder cancer: a 10-year follow-up
J Urol
(1992)
NadlerRB et al.
Durability of the tumor-free response for intravesical bacillus Calmette-Guérin therapy
J Urol
(1994)
WajsmanZ et al.
Bladder-sparing approach in the treatment of invasive bladder cancer
Semin Urol
(1990)

There are more references available in the full text version of this article.

Cited by (77)

Effectiveness of Transurethral Resection plus Systemic Chemotherapy as Definitive Treatment for Muscle Invasive Bladder Cancer in Population Level Data
2018, Journal of Urology
We investigated the characteristics and outcomes of patients with muscle invasive bladder cancer treated with transurethral resection plus chemotherapy alone in a large observational cohort reflecting the continuum of practice settings in the United States.
In the National Cancer Database from 2004 to 2015 we identified 1,538 patients treated with transurethral resection plus multi-agent chemotherapy as definitive treatment of cT2-T4aN0M0 urothelial carcinoma of the bladder. For comparison purposes we included in study 17,866 patients treated with radical cystectomy with or without perioperative chemotherapy. Baseline characteristics were compared between the 2 groups by multivariable logistic regression. Treatment outcomes were assessed using Kaplan-Meier analysis and a Cox regression model.
On multivariate analysis several variables, including patient demography (older age, African American race, prior malignancy and lack of insurance), tumor characteristics (higher cT stage) and facility type (nonacademic facilities and lower radical cystectomy volume) were associated with a higher probability of transurethral resection plus chemotherapy for muscle invasive bladder cancer compared to the standard of care. Two and 5-year survival rates in all patients treated with transurethral resection plus chemotherapy were 49.0% and 32.9%, and in patients with cT2 disease the rates were 52.6% and 36.2%, respectively.
This large population level cohort of unselected patients shows that long-term survival can be achieved in a subset of patients treated with transurethral resection plus chemotherapy alone for muscle invasive bladder cancer. However, the best candidates for this approach remain to be defined. Ongoing clinical trials are now being launched to evaluate the ability of biomarkers to accurately select patients who could be treated with this bladder sparing strategy.
A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer
2018, Urologic Oncology: Seminars and Original Investigations
Citation Excerpt :
Likewise, in studies that used a radiation dose of 60–66 Gy [7,9,11,20,22,26,28,30,34,41,42], there was no difference in the rate of CR for TMT studies using a radiation dose ≥60 Gy vs.<60 Gy (71.7% vs. 71.2%, P = 0.49) [25,29,31,35,36,39]. In TMT studies that used NAC plus TMT [7,8,23,24,38], the mean CR was not significantly higher for TMT plus NAC compared to TMT alone (76.2% vs. 73.0%, P = 0.33) [10,11,20–22,25,26,28–32,34–36,39,41,42]. In the studies reporting on RC after TMT [7–11,21–25,28–32,34–40,45], there were 360 (17.5%) of 2,053 patients who were subjected to RC after TMT.
This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC).
A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed.
The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3–4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively.
In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.
Endoscopic Treatment of Bladder Tumors
2016, Endoscopic Diagnosis and Treatment in Urinary Bladder Pathology: Handbook of Endourology
Although bladder tumors were first described in 1551 by Lacuna, lack of diagnostic accuracy meant efficient therapies could not be developed. Therefore, although occasional excisions of tumoral masses discovered during lithotomy were reported, the first operations for bladder tumors were not performed until the seventeenth century. These were limited to urethral tumors or tumors of the bladder neck in women. Endoscopic visualization of the urethral lumen allowed Desormeaux to extract a urethral papilloma through a urethroscope.
Radical cystectomy versus organ-sparing trimodality treatment in muscle-invasive bladder cancer: A systematic review of clinical trials
2015, Critical Reviews in Oncology/Hematology
Radical cystectomy (RC) represents the mainstay of treatment in patients with muscle-invasive urinary bladder cancer but how it compares with the best organ preservation approach is not known.
The objective of our review is to compare the 5-year overall survival (OS) rates from retrospective and prospective studies of RC and trimodality treatment (TMT), i.e. concurrent delivery of chemotherapy and radiotherapy after a transurethral resection of bladder tumor (TURBT), involving a total of 10,265 and 3131 patients, respectively. We used random-effect models to pool outcomes across studies and compared event rates of combined outcomes for TMT and RC using an interaction test.
The median 5-year OS rate was 57% in the TMT group, when compared with 52% (P = 0.04), 51% (P = 0.02) and 53% (P = 0.38) in the whole group receiving RC or the group treated with RC alone or RC + chemotherapy, respectively. The hazard risk (HR) of mortality of patients treated with TMT or RC was 1.22 (95% CI = 1.13–1.32) with an absolute benefit of 5% in favor of the former. The HR of mortality from TMT persisted significantly better not only versus the group treated with RC alone (HR = 1.22; 95% CI = 1.12–1.32), but also versus the group receiving RC + chemotherapy (HR = 1.22; 95% CI = 1.09–1.36). Multivariate analysis confirmed TMT as a significant prognostic variable for both RC alone and RC + chemotherapy.
Compared with RC, TMT seems to be associated with a better outcome for patients with muscle-invasive bladder cancer (MIBC). The addition of chemotherapy may improve the RC outcome in some subgroups of patients with a higher probability of micrometastases. Prospective randomized trials are urged to verify these findings and better define the role of organ preservation and radical treatment strategy in the management of patients with MIBC.
A systematic review and meta-analysis of clinical trials of bladder-sparing trimodality treatment for muscle-invasive bladder cancer (MIBC)
2015, Critical Reviews in Oncology/Hematology
Despite the numerous prospective and retrospective studies published during the last 2 decades aiming at testing the safety and the efficacy of trimodality therapy (TMT) as a conservative treatment, an optimal therapeutic strategy has not yet been identified. We made a systematic overview of the 5-year outcomes from 31 trials of combined chemotherapy and radiation (CRT) after transurethral resection of muscle-infiltrating bladder tumours (TURBT), the so-called trimodality therapy. We took into consideration the results of each trial i.e. the rate of complete response (CR), local muscle-invasive local failure (LF), salvage cystectomy (SC), 5-year overall survival (OS) and 5-year bladder intact survival (BIS) from 3315 patients.
About half of the patients were treated with a preliminary induction followed by a consolidation CRT course in CR, or SC in non-CR patients (split treatment). The remaining half of the patients underwent an upfront full-dose CRT course (continuous treatment) with SC reserved to non-CR patients. Excellent results were obtained by trimodality therapy (TMT), with 78% CR, 28% muscle infiltrating LF and 21% SC in patients with MIBC. The 5-year OS and BIS rates were 56% and 42%, respectively. At univariate analysis, CR, and SC rates appeared to be significantly better in the continuous than in the split treatment group. Multivariate analysis confirmed the former regimen as a significant prognostic variables only for CR, while CP-based regimen was a significant prognostic factor for SC. The subgroup analysis revealed a significant improvement in 5-year OS rate of continuous over split treatment in later stage tumours. No relevant benefit was observed with the addition of other drugs to cisplatin (CP) or neo-adjuvant chemotherapy (NATC) to CRT, although, in patients receiving NACT, significantly better CR and OS rates were seen in the continuous than split treatment.
The results of this overview seem to indicate that TMT is able to produce excellent 5-year OS rates, no matter how it is done (continuous or split). No significant difference in 5-year OS rates could be observed between the two treatment regimens, although the continuous may offer some advantage compared to split treatment in terms of higher CR and, likely lower SC rates. The highest benefit might be achieved in later stage tumours, using a total radiation equivalent dose when delivered in 2 Gy/fraction (EQD2) of more than 60 Gy in combination with CP based regimes and preceded by 2–3 NACT cycles. Appropriate randomized trials should be addressed to confirm the results of the present review.
Trimodality treatment in the conservative management of infiltrating bladder cancer: A critical review of the literature
2013, Critical Reviews in Oncology/Hematology
Although radical cystectomy is still the treatment of choice for patients with infiltrating bladder cancer, there is growing evidence of the effectiveness of a conservative approach. Developed as a treatment of need for elderly or unfit patients unable to undergo radical cystectomy, conservative therapy is becoming a true alternative to surgery for highly selected patients. Although transurethral bladder resection, external radiotherapy and systemic chemotherapy can control the disease as single treatments, the best results have been observed when they are combined. Moreover, new irradiation techniques and new-generation drugs are now being tested in an attempt to improve disease control further. Conservative management requires the multidisciplinary involvement of different specialties in order to give patients a real alternative to surgical treatment.

View all citing articles on Scopus

View full text

Bladder-sparing multimodality treatment of muscle-invasive bladder cancer: A five-year follow-up

Abstract

Objectives

Methods

Results

Conclusions

Int J Radiat Oncol Biol Phys

J Urol

J Urol

Bladder-sparing approach in the treatment of invasive bladder cancer

Semin Urol