Intensity-Modulated Radiotherapy Of The Prostate After Cryotherapy: Initial Experience

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology
Article Date: 02 Jul 2008 - 0:00 PDT

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UroToday.com - Cryotherapy has benefited from many technical advances in recent years. "Third generation" delivery systems have significantly decreased the rate of complications resulting in a renewed interest in cyrotherapy for treatment of localized prostate cancer.

Unfortunately, PSA control still remains suboptimal. 5yr PSA failure rates range from 60-87% for low risk patients and are even higher for intermediate and high risk patients. A significant portion of these patients will fail locally. The optimal management of these patients has not been elucidated.

Salvage options included repeat cryotherapy, radical prostatectomy, and radiation therapy. Repeat cryotherapy has been reported with higher complication rates, and salvage prostatectomy after complete cryoablation is extremely difficult due to tissue reaction and fibrosis.

Radiation is thus an attractive salvage option; however, limited data regarding this approach has been published. Previously, only two small series of salvage radiation following cryotherapy have been published. Both of these series have shown encouraging results but have used low doses of < 70 Gy and older radiation techniques. In the definitive management of localized prostate cancer, it is now well established via several randomized trials that dose escalation to > 70 Gy improved PSA control.

In our study, we report the first published experience of high dose radiation therapy following cyrotherapy. Modern radiation techniques were used for all patients. Radiation was delivered using intensity modulated radiation therapy (IMRT) with daily image guidance, i.e. image guided radiation therapy (IGRT). This allowed delivery of the same high radiation doses we use for the treatment of prostate cancer in the absence of prior cyrotherapy. A minimum target dose of 73 Gy was used resulting in a mean target dose of > 75 Gy.

Our study shows, with a median follow up of almost 3 years, that the rate of late toxicity was not elevated above what would be expected for radiation treatment in the absence of prior cyrotherapy. No grade 3 or greater late toxicity was seen. Only 2 patients developed grade 2 late toxicity, both of whom had resolution of their symptoms with conservative interventions. This study thus supports the use of salvage irradiation using modern IGRT techniques following cryotherapy failure. The PSA control in our study is encouraging, but the length of follow up and small series size precludes making any outcomes conclusions.

Although cryotherapy alone appears to have suboptimal results compared with other treatment modalities for localized prostate cancer, an intriguing approach is to combine cyrotherapy and radiation as an initial approach. Oncologic cyto-reduction with surgical techniques followed by radiation therapy is a standard approach for many malignant diseases. Cyto-reduction is a fundamental radiobiological principle. Radiation therapy eradicates tumor cell in a statistical fashion following an exponential function. Thus, starting with fewer tumor clonogens the probability of eradication of all clonogens, i.e. cure, is increased at a given radiation dose. Furthermore, areas of bulk disease harbor hypoxic tumor cells which are relatively radiation resistant by a factor as high as three. Eliminating these areas prior to radiation therapy would thus further increase the probability of cure. Based on our study it appears that the combination of cryotherapy followed by radiation therapy is well tolerated without an elevated risk of late side effects. This combined approach is intriguing and warrants further investigation.

Written by Jaroslaw T. Hepel, MD, and Thomas DiPetrillo, MD, as part of Beyond the Abstract on UroToday.com.

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