麻豆传媒

Results from a small prospective Indian study suggest that dose-escalated image-guided radiation therapy (IGRT) could replace radical cystectomy as the standard of care for bladder preservation in localized muscle-invasive bladder cancer.

Reporting , , of Tata Memorial Centre in Mumbai, found an 83% rate of bladder preservation at 3 years in 44 patients treated with IGRT, and acute and late toxicities were lower than with conventional radiation therapy.

Enrolled during 2008-2014, the 44 adult patients (median age 64, 39 female) with stages T1 to T4 disease underwent maximal resection of their tumors and concurrent platinum-based chemotherapy. Those with larger tumors were offered induction chemotherapy.

Most patients (88%) had T2 disease, and 16 (36%) received neoadjuvant chemotherapy. Prophylactic nodal irradiation was administered to 73%, and 55% of the patients received an escalated dose to the tumor bed.

Patients received 64 Gy in 32 fractions to the whole bladder, 55 Gy to the pelvic nodes, and, if appropriate, a simultaneous integrated boost to the tumor bed of up to 68 Gy. Daily megavoltage imaging helped select the most appropriate planning target volumes bladder for each particular day of treatment.

With a median follow-up of 30 months, the 3-year locoregional control, disease-free survival, and overall survival were 78%, 66%, and 67%, respectively. Locoregional control was significantly better for younger patients (P=0.01).

The 3-year rates in this prospective study for overall survival and bladder preservation were similar to those seen in other recent studies including one and .

Results were better with dose escalation than without: locoregional control 87% versus 68% (P=0.748) and overall survival 74% versus 60% (P=0.36).

As for adverse effects, 34% of series patients had grade 2 acute genitourinary toxicity, and 27% had grade 2 gastrointestinal toxicity. Acute and late grade 3 genitourinary toxicity was seen in 11% and 4%, respectively, while no acute or late grade 3 or higher gastrointestinal toxicities occurred.

All patients had a complete response 6 to 10 weeks after treatment, and 34 were alive at last follow-up; of these 32 were disease-free. Among the 10 deaths, three were due to comorbidities in patients who were disease-free at the time of death.

Isolated muscle-invasive local recurrence occurred in three patients and superficial recurrences were seen in two patients. Regional nodal failures occurred in two patients, neither of whom received prophylactic nodal irradiation. These were treated with salvage pelvic nodal irradiation to 40 Gy in 16 fractions with IGRT using tomotherapy.

The authors said the results with adaptive IG-IMRT were "clinical proof of the dosimetric concept of adaptive RT."

Among the study's limitations, Murthy and associates cited the relatively short follow-up period, acknowledging that further follow-up may see more failures. The unavailability of quality of life data was also a drawback, they wrote.

Commenting on the study for 麻豆传媒, , of Washington University in St. Louis, said, "I believe a larger experience with longer follow-up will be welcome, but we already know that combined chemotherapy and radiation therapy in properly selected patients is an effective alternative to radical cystectomy. This new approach of IG-IMRT and adaptive radiation therapy can only improve on those results."

Michalski added that one of the challenges with intensity-modulated radiation therapy (IMRT) in bladder cancer has been the variation in target volume position during a course of therapy. "The bladder is one of the most variable and mobile organs in the pelvis, and traditional radiation techniques were obligatorily large to reassure the treating physician that the tumor was in the radiation field," he said.

IMRT requires precise knowledge of tumor location and reproducible positioning of patient and target, and image-guided IMRT is now being evaluated in bladder cancer using daily cone beam computed tomography. "Other new technologies such as [magnetic resonance]-guided RT or implanted radio-opaque bladder wall markers are making daily adaptive radiation therapy a reality," Michalski said.

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