The potential for normal tissue dose reduction with neoadjuvant hormonal therapy in conformal treatment planning for stage C prostate cancer.
OBJECTIVE
Preirradiation hormonal cytoreduction of prostate cancer has been proven to reduce exposure of normal structures by decreasing the size of the target volume. Dose-volume histogram (DVH) analysis, however, does not always appear to demonstrate a strong positive benefit with the use of neoadjuvant hormone therapy. This study analyzes various other factors influencing dose to normal organs, which may determine the success or failure of neoadjuvant hormonal therapy in achieving its goals.


METHODS
Patients with bulky clinical Stage C adenocarcinoma of the prostate were given 3 months of hormone treatment consisting of oral Flutamide and monthly Zoladex injections prior to irradiation. Computerized tomography (CT) scans of the pelvis were obtained both prior to and following hormonal treatment. Treatment plans were generated by three-dimensional (3D) conformal treatment planning. The change in the volume of the prostate was assessed along with the percentage of prescribed dose delivered to the rectum and bladder. Various factors such as prostate size, bladder/rectum size, and organ shape were studied. Both dose-volume histograms (DVH) and dose-surface area histograms (DSH) were used for analysis.


RESULTS
Six of seven patients had reduction in the size of their prostates. The mean volumes of the prostate before and after hormonal manipulation were 129.1 +/- 32.9 standard deviation (SD) cm3 and 73.0 +/- 29.5 SD cm3, respectively (p = 0.0059). The volume of rectum receiving 80% of the prescribed dose was reduced in five of seven patients from a mean of 83.2 to 59.9 cm3 (p = 0.045). The volume of bladder receiving 80% of the prescribed dose was also reduced in five out of seven patients from a mean of 74.5 to 40.2 cm3 (p = 0.098). Correlation between the size of the prostate and volume of rectum and bladder treated was not always consistent: greater reduction in prostate size did not necessarily result in large decreases in dose to bladder or rectum. The total size of the bladder and rectum were found to be important factors in normal tissue radiation exposure; the benefits of hormone therapy may be lost if the bladder and rectum are allowed to decrease in size. Also, the bladder may be prone to sagging into the pelvis of some patients following hormone therapy, resulting in a less optimal therapeutic ratio.


CONCLUSIONS
Reduction in prostate size by neoadjuvant hormonal manipulation does decrease the amount of normal tissue irradiated in most patients. However, the correlation between the reduction in prostate size and amount of rectum or bladder treated is not linear if other variables are not controlled. Factors such as the shape of the organs, as well as the distensible nature of the bladder and rectum, play major roles in dose to normal tissues. These facts may mask the benefits of cytoreduction and could be obstacles in realizing consistent benefits from preirradiation hormonal treatment in the clinical setting if they are ignored.
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005485:Flutamide / Q000627:therapeutic use*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012007:Rectum / Q000473:pathology; D012189:Retrospective Studies; D001743:Urinary Bladder / Q000473:pathology
D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D005485:Flutamide