Japanese Journal of Clinical Oncology 30:553-556 (2000)
© 2000 Foundation for Promotion of Cancer Research
Preoperative Concurrent Chemoradiotherapy Against Muscle-invasive Bladder Cancer: Results of Partial Cystectomy in Elderly or High-risk Patients
Department of Urology and Reproductive Medicine, Graduate School Tokyo Medical and Dental University, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: Good local control has been reported in cases of muscle-invasive bladder cancer treated by chemoradiotherapy and transurethral resection (TUR). However, definitive irradiation or extensive chemotherapy is often intolerable for elderly or poor-risk patients. We report here benefits of partial cystectomy after concurrent low-dose chemoradiotherapy for high-risk patients.
Methods: Thirty-seven patients with localized muscle-invasive bladder cancer (T2–T4) were treated with concurrent cisplatin (50–100 mg/body x 2 courses) and pelvic irradiation (40 Gy) preoperatively. Among 17 patients (46%) who achieved complete response (CR), 10 were not suitable for radical cystectomy and underwent partial cystectomy. Radical cystectomy was performed in 24 cases [CR = 6, partial response (PR) = 18]. Two patients (one CR and one PR) rejected open surgery and were treated by TUR of the primary site. One no change (NC) patient received no further treatment because of mental disorder.
Results: Median follow-up was 12 months (range 2–37 months). Fifteen of 36 evaluable cases (42%) achieved a pathological T0 response (no residual tumor). Estimated 3-year disease-free survival was 56% for all patients and 100% for T0 responders. Seven of 21 patients with pathological persistent tumor developed local recurrence (three patients) or distant metastasis (four patients). All of the 10 patients (eight with T0 response and two with a small residual tumor nest) who underwent partial cystectomy were recurrence-free for an observation period of up to 3 years.
Conclusions: Bladder preservation by partial cystectomy may be a choice for patients who show a good response to preoperative chemoradiotherapy and are not suitable for radical cystectomy.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Treatment of muscle-invasive bladder cancer in elderly or high-risk patients is a challenging problem. In many cases, radical surgery is not tolerable. It is often difficult to complete combination chemotherapy or extensive radiotherapy because of impaired compliance. Recently, several authors have reported promising results of concurrent radiochemotherapy using cisplatin (1–6). Pelvic failure is less common than with radiation monotherapy (6). The survival rate matches that of radical cystectomy (7) and a functional bladder can be retained in many cases. Since 1997, we have been applying radiotherapy concurrent with cisplatin for muscle-invasive bladder cancer to control local disease before radical cystectomy. In elderly or high-risk patients who achieved clinical complete response (CR) and were unsuitable for extensive therapy, the bladder was preserved by partial cystectomy. We report here the favorable short-term outcome of our protocol, especially in poor-risk patients who underwent partial cystectomy.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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From March 1997 to May 2000, 37 patients with muscle-invasive bladder cancer without apparent metastasis were consecutively treated with concurrent chemoradiotherapy. Case profiles are described in Table 1. The median age was 71 years (range 45–83 years). Twenty-four were men and 13 were women. Staging procedures included cystoscopy, chest radiography and computerized tomography (CT) or magnetic resonance imaging of the abdomen and pelvis. Clinical T stage was determined based on the findings of biopsy and CT scan according to the 1997 International Union Against Cancer classification (8). Histological grade was determined according to the Japanese Urological Association classification (9).
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Pelvic irradiation was given at a dose of 40 Gy (plus an additional 10–20 Gy to the bladder in five cases with massive tumor) in 4–5 weeks. Systemic (10–20 mg/day for 5 days) or intra-arterial (50–100 mg) administration of cisplatin was performed during weeks 1 and 4 of radiation therapy. The dose of cisplatin was reduced depending on the patient’s renal function or general condition.
Responses to radiochemotherapy were defined based on the findings of CT scans and cystoscopy as follows: CR, no visible tumor; partial response (PR), 
50% reduction in tumor volume; no change (NC), <50% decrease or <25% increase in tumor volume. Radical cystectomy, partial cystectomy or transurethral resection (TUR) was performed 1 month after the end of chemoradiotherapy depending on the clinical response and the condition of the patient.
Local control and survival were calculated according to the Kaplan–Meier method. Pathological T0 response was defined as either a negative biopsy at the initial tumor site (for the TUR group) or surgical specimen free of cancer cells (for radical or partial cystectomy). Treatment-related toxicity was assessed according to the World Health Organization criteria (10)
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Toxicity noted during chemoradiotherapy was mild and consisted of grade 1–2 nausea/vomiting, grade 1–3 diarrhea and grade 1–3 myelosuppression. Clinical CR was achieved in 17 patients (46%), whereas 19 showed PR and the remaining one was NC. Radical cystectomy was performed in 24 cases (CR = 6, PR = 18), as shown in Table 2. Ten patients with CR underwent partial cystectomy. Among them, six patients were elderly (80–83 years old), three showed impaired performance status and the remaining one was reluctant to receive radical surgery. Two patients (one CR and one PR) refused open surgery and were treated by TUR of the primary site. One patient (NC) received chemoradiotherapy alone because of severe mental disorder.
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Estimated overall disease-free 3-year survival for these 36 patients was 56% (Fig. 1). As described in Table 2, pathological T0 response was obtained in 15 of them (42%). All of the T0 responders were free of disease for the entire observation period. Seven (40%) of 21 patients with pathological residual tumor developed local recurrence (three patients) or distant metastasis (four patients) (Fig. 2). There were five cancer-related deaths due to distant metastasis in four and local extension in one. None of the patients died of disease other than bladder cancer.
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No recurrence was noted in the partial cystectomy group (eight T0 responders and two with a residual tumor nest) for an observation period of up to 37 months (median 12 months), as shown in Fig. 3. Profiles of the patients in the partial cystectomy group are given in Table 3. Although urinary frequency due to low bladder capacity was noted in all of the 10 cases, the symptoms eased gradually and bladder function was recovered by 1 year after operation. One of the two patients with a small nest of residual cancer cells was the longest survivor and free of relapse for 37 months with normal bladder capacity and control. Case 6 was an elderly patient with hemiplegia and impaired renal function. Only 20 mg of cisplatin was used during 40 Gy radiation. Nevertheless, the pathological response was excellent (no residual cancer) and the patient’s performance status was not impaired with a normal functioning bladder.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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We obtained excellent local control and short-term survival by concurrent chemoradiotherapy even in elderly or high-risk patients. It is difficult to perform extensive radiotherapy or combined systemic chemotherapy in such cases because of co-existing pulmonary or cardiovascular disease. Although the dose of cisplatin in our study was smaller than that in other reports employing similar protocols, our CR rate (46%) matches those reported (47–69.7%) (6,11,12). Low-dose cisplatin plus concomitant 40 Gy radiation is less time consuming and less toxic than extensive radiotherapy, systemic combined chemotherapy or a combination of both. Our protocol may be applicable to poor-risk patients once considered untreatable by conventional therapy.
Although long-term observation is necessary, the short-term disease-free survival of the partial cystectomy group was much better than expected. In the current study, partial cystectomy was applied only to the patients with clinical CR. This may explain our favorable outcome because CR by the end of chemotherapy or chemoradiotherapy has been demonstrated to be the most significant predictor of survival (11,13). Partial cystectomy may be a choice against muscle-invasive bladder cancer in elderly or high-risk patients who showed CR to the preoperative chemoradiotherapy.
Preservation of the bladder by TUR is always hampered by the risk of understaging and requires additional irradiation for consolidation after induction chemoradiotherapy. On the other hand, partial cystectomy allows a thorough examination of the original tumor site and provides a more precise evaluation of the response. Pelvic lymphadenectomy, if necessary for accurate staging, can be done concomitantly. In addition, it precludes the need for consolidation radiotherapy. With these benefits, partial cystectomy after chemoradiotherapy may be beneficial for elderly or high-risk cases in which preservation of the bladder is desirable.
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FOOTNOTES |
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+ For reprints and all correspondence: Yukio Kageyama, Department of Urology and Reproductive Medicine, Graduate School Tokyo Medical and Dental University, 1–5–45 Yushima, Bunkyo-ku, 113-8519 Tokyo, Japan. E-mail: kageyys.uro@tmd.ac.jp
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REFERENCES |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Received August 10, 2000; accepted October 10, 2000.
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