Frontiers ofradiation Therapy and Oncology Reprint Editors: J.M. Vaeth, J.L. Meyer, San Francisco, Calif. ~' Publishers: S.Karger, Basel Printed in Switzerland Vaeth JM, Meyer JL (eds): The Role of High Energy Electrons in the Treatment of Cancer. Front Radiat Ther Oncol. Basel, Karger, 99, vol 25, pp 37-32 Intraoperative Radiation Therapy for Prostatic Cancer Mitsuyuki Abe*, Masaji Takahashi0, Yuta Shibamoto*, Koji Onoa "Department of Radiology, Faculty of Medicine, and bchest Disease Research Institute, Kyoto University, Kyoto, Japan External beam radiation therapy (EBRT) has played a major role in the management of prostatic cancer []. It has been demonstrated, how ever, that prostatic irradiation of 65-72 Gy with or without pelvic irradia tion of 45-50 Gy produced an overall complication rate of 24% [4], with an approximately 0% incidence of rectovesical injuries [6]. Intraoperative radiation therapy (IORT) using electron beams with a sharp and rapid-fall off in depth dose is of particular advantage in the treatment of localized prostatic tumors because exposure to the bladder and the rectum can be minimized. Materials and Methods Twenty-one patients with prostatic adenocarcinoma were treated with IORT at the Kyoto University Hospital. IORT was given either alone or in combination with EBRT. Eleven patients had stage C disease, 4 stage B2> 3 stage Dj, 2 stage B,, and stage A2. Six patients received only IORT, while 5 received IORT in combination with EBRT to the pelvis including the prostate. Early in this series, single doses of 28-35 Gy were delivered with electron beams. The electron energiesranged from 8 to 4MeV depending on tumor size. More recently, IORT was applied as a boost therapy in conjunction with EBRT, in which 50 Gy was delivered to the whole pelvis including the prostatic lesion in conventional fractions of.8-2.0 Gy/day, 5 treatments/week in most cases. The main reason is that the incidence of pelviclymph node metastases with prostatic cancer ranges from 7 to 36% in stage B and from 38 to 69% in stage C [2, 3, 5]. The procedure of IORT for prostatic cancer was reported in a previous publication [7]. Briefly, the patient is placed in the exaggerated lithotomy position, and an inverted U-shaped incision is made in the perineum. Dissection is continued upwards to achieve direct exposure of the prostatic tumor and to separate the posterior surface of the tumor from the rectum. A Young's retractor is then passed via the urethra into the bladder. By pulling the handle of the
Abe/Takahashi/Shibamoto/Ono 38 retractor in a cranial direction, the prostatic tumor can then be pushed towards the perineum with the pubis acting as a fulcrum. The tumor is then positioned within a sterile treatment cone which is inserted through the perineal incision. Selection of the electron energy is made depending upon the depth of the lesion, so that the whole tumor can be covered within the 90% isodose curve. Evaluation of the tumor response was made on the basis of serial rectal examinations, retrograde urography, CT scan, or perineal needle biopsy. Tumors were graded as complete regression (CR), partial regression (PR), and no response (NR). CR was defined as the clinical disappearance of the tumor, PR as a reduction of > 50% in the tumor volume, and NR as a <50% decrease. Results Survival Table shows the stage distribution and the tumor response accord ing to stage. Of the 2 patients, 7 achieved CR (80.9%). The correlation between radiation dose and tumor response is demonstrated in table 2. In the patient who received a single dose of 28 Gy, IORT failed to achieve local control. In the patient in whom CR was achieved by an IORT dose of 30 Gy, there was no histological evidence of recurrence for 5 years after IORT. In the 6th year, however, biopsy showed local recurrence of disease in the IORT field. Four patients received single doses of 33-35 Gy, and it was confirmed by needle biopsy that local control was achieved during the follow-up period of 2-8 years. In 3 out of 5 patients treated by IORT (20-33 Gy) plus EBRT (30-60Gy/4-7 weeks), local control was achieved. The cumulative survival curve is shown in figure. The 5-year survival rate of the whole 2 patients was 72.0%, and that of the patients with stage C disease was the same. Table. Stage distribution and clinical response according to stage Stage Patients, n Clinical response A2 CR B, 2 CR in 2 B' 4 CR in 3, PR in q CR in 9, PR in 2 D 3 CR in 2, PR in Total 2 CR 7, PR 4
3 Survival Intraoperative Radiation Therapy for Prostatic Cancer o8 Table 2. Tumor response by tumor dose given by IORT with or without EBRT 39 Dose Gy- Patients, n Local recurrence IORT EBRT _ - - 28 positive 30 negative, 5 years, positive at the 6th year 33 negative in 3 35 negative 20 50 negative 25 30 negative 25 50 negative in 9 25 60 negative 33 50 negative Total 2 negative 7, positive 4 00-90- 80-70-?.-..!,_ i 72.0% 60-50- 35 40- Stage kz i (n = 2) ]3 30- Stage C (n = )!_...... r " i r 2 3 4 5 Survival time, years Fig. I. Survival figures (Kaplan-Meier) of prostatic cancer patients treated by IORT. Complications Hematuria was observed in all patients after IORT. It lasted for 2-4 weeks in patients treated with IORT doses of 28-35 Gy, and for -2 weeks in those treated with IORT doses of 20-25 Gy in combination with an EBRT dose of 50 Gy. Hematuria was attributed not only to the IORT itself, but also to the manipulation of the Young's retractor inserted in the urethra. All of the patients recovered and had no recurrence of the symptom.
Abe/Takahashi/Shibamoto/Ono 320 Pollakiuria developed in 2 patients who were treated by IORT plus EBRT. One patient, who received IORT (25 Gy) plus EBRT (60 Gy), developed a contracted bladder. Urethral stricture developed in patient who received an EBRT dose of 30 Gy plus an IORT dose of 25 Gy. In the other patient treated with IORT (25 Gy) plus EBRT (50 Gy), the pollaki uria resolved within 6 months and there was no recurrence. Discussion During the follow-up period of 32-52 months, local control was achieved and maintained in 7 patients, but the remaining 4 failed locally. Since 4 local failures appeared to be due to inadequate IORT planning or technique (low electron energy or an insufficient radiation field), it seems that the local control rate can be improved in the future. When IORT is used for patients without pelvic lymph node metastasis, single doses of 33-35 Gy depending upon the tumor volume appear to be optimal, because local control was achieved and maintained at these doses without serious complications in our series. However, for patients with suspected pelvic lymph node metastasis, it is recommended that an IORT Prostatic cancer EBRT 50 Gy to whole pelvis IORT 25 Gy to tumor IORT 33-35 Gy to tumor IORT 25 Gy to prostatic tumor EBRT 50 Gy to whole pelvis Fig. 2. IORT schema for prostatic cancer.
Intraoperative Radiation Therapy for Prostatic Cancer 32 dose of 25 Gy should be delivered in combination with an EBRT dose of 50 Gy to the whole pelvis including the prostatic tumor. As there was a problem with delayed wound healing of the perineal incision in 2 patients treated by IORT following EBRT, it is recommended that EBRT be delivered after IORT. However, if the tumor size is larger than 4 cm in diameter, the tumor can hardly be covered with a safety margin by a treatment cone. In such a case, EBRT should be given before IORT in an attempt to reduce the tumor size so that an IORT field can cover sufficiently the tumor. Our findings suggest that local control with minimal morbidity can be obtained by the use of IORT in patients with locally advanced prostatic cancer. Our IORT policy for prostatic cancer is demonstrated in figure 2. References Bagshaw, M.A.; Kaplan, H.S.; Sagerman, R.H.: Linear accelerator supervoltage radio therapy. VII. Carcinoma of the prostate. Radiology 85: 2-29 (965). Bagshaw, M.A.; Ray, G.R.; Pistenma, D.A.; Castellino, R.A.; Meares, E.M.: External beam radiotherapy of primary carcinoma of the prostate. Cancer 36: 723-728 (975). Hilaris, B.S.; Kim, J.H.; Tokita, N.: Lowenergy radionuclides for permanent interstitial implantation. Am. J. Roentgenol. Radiat. Ther. Nucl. Med. 26: 7-78 (976). Kurup, P.; Kramer, T.S.; Lee, M.S.; Phillips, R.: External beam irradiation of prostatic cancer. Cancer 53: 37-43 (984). Perez, C.A.; Baner, W.; Garza, R.; Royce, R.K.: Radiation therapy in the definitive treatment of localized carcinoma of the prostate. Cancer 40: 425-433 (977). Pilepich, M.V.; Krall, J.; George, F.W.; Asbell, S.O.; Plenk, H.D.; Johnson, R.J.; Stetz, J.; Zinninger, M.; Walz, B.J.: Treatment-related morbidity in phase III RTOG studies of extended field irradiation for carcinoma of the prostate. Int. J. Radiat. Oncol. Biol. Phys. 0: 86-867 (984). Takahashi, M.; Okada, M.; Shibamoto, Y.; Abe, M.; Yoshida, O.: Intraoperative radiotherapy in the definitive treatment of localized carcinoma of the prostate. Int. J. Radiat. Oncol. Biol. Phys. : 47-5 (985). M. Abe, Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto 606 (Japan)