Late results in patients treated with pi-mesons for bladder cancer.

ABSTRACT

BACKGROUND: The treatment of bladder cancer with 60 converging pion beams was expected to have certain dose-distribution advantages with possibly fewer side effects than other high linear-energy-transfer (LET) radiation therapies, such as neutrons. RESULTS: Early results were promising 20 of 24 (83%) evaluable patients with sessile invasive bladder carcinomas had clinically complete responses. However, only 3 of 10 (30%) evaluable patients with superficial bladder tumors had clinically complete responses. This article reports the long-term follow-up (6-8 years) of these patients with emphasis on the late side effects of pion radiation therapy. Thirty-eight of the 41 (93%) patients treated died after a median survival time of 17 months (range, 4-98 months). Seventeen (45%) died of metastatic disease (in two instances, this was combined with a local recurrence) 5-27 months after radiation therapy. Four (10%) died of locally progressive disease, and eight (21%) died of late side effects of radiation therapy 9-98 months after treatment. All these patients were treated with more than 33 pion Gy and had generally a symptom-free interval of 9-18 months. The observed side effects were severe, consisting of chronic inflammation and vascular damage in the pelvic region often followed by ulceration, fistulas, and perforations throughout the intestines. In 11 patients, cystectomy and urinary diversion was necessary because of excessive fibrosis and bladder shrinkage. In eight patients, a colostomy was required for stenotic inflammatory disease, necrosis, and perforations of the intestines. The remaining nine patients (24%) died of causes unrelated to the primary disease 4-60 months after radiation therapy. CONCLUSIONS: The results of the first Phase I/II trial using the Swiss piotron showed a high complete response rate in patients with sessile bladder cancers but also a high incidence of local recurrences and severe, in some instances lethal side effects. Although it is expected that these results will be the basis for future improvements, particularly regarding dosing and fractionation, this experience emphasizes the need for a sufficiently long observation period before reaching conclusions about any high LET treatment, such as neutron, pion, or heavy ion radiation therapy.