International Journal of Radiation Oncology*Biology*Physics
Clinical investigationProstateIncreased Risk of Biochemical and Clinical Failure for Prostate Patients with a Large Rectum at Radiotherapy Planning: Results from the Dutch Trial of 68 GY Versus 78 Gy
Introduction
In the past decades, conformal radiotherapy (RT) has become the standard treatment technique for prostate cancer. This “high dose, high precision” treatment requires accuracy within millimeters with regard to delineation of the target, patient setup, and organ motion, because the current clinically applied margins are in the range of 8–15 mm (1, 2, 3). This also implies that the anatomic patient model available from the planning CT scan should be representative of the situation during the treatment period. In 2005, Dearnaley et al. (1) published data from a pilot study in which they had randomized patients between a standard and high radiation dose and between a 1-cm or 1.5-cm margin. Their results showed no decrease in tumor control for the 1-cm margin compared with the 1.5-cm margin, implying that a 1-cm margin is “safe” during conformal RT. Recently, de Crevoisier et al. (4) published data in which they concluded that the applied margins of 7.5–15 mm to the block edge for the boost were not safe for patients with a distended rectum visible on the planning CT scan. They noted a decrease of almost 30% in tumor control for the subgroup with a cross-sectional area (CSA) of the rectum greater than the median value of 11 cm2. In a previous study of our own group, Hoogeman et al. (5) studied the rotational position of the prostate as a function of rectal volume. In their study, the data of 19 patients for whom a planning CT scan was available, as well as 10 repeat CT scans (during treatment), were analyzed. The rectal volume on the repeat CT scans appeared to be smaller than on the planning CT scan (average 74 cm3 and 84 cm3, respectively), causing an average systematic displacement (rotation) of the prostate during treatment. These data showed that a rectal volume of ≥ 90 cm3 on the planning CT scan was associated with a rotation of at least 2° around the left–right axis. The position of the prostate on the repeat CT scans showed that a rotation of the prostate caused by a smaller rectum was associated with a rotation of the base of the seminal vesicles (SVs) out of the planning target volume for several patients. A smaller rectal volume during treatment with regard to the situation on the planning CT scan can be explained by the development of loose or watery stools during RT for a large group of prostate cancer patients. Published data on diarrhea during RT are limited; toxicity is mostly reported in terms of overall toxicity scores and/or increased stool frequency, proctitis, and bleeding and not in terms of diarrhea. The prevalence of diarrhea during RT for prostate cancer was reported by de Meerleer et al. (6) to be 31% (72–78 Gy, 2 Gy/fraction). A much greater frequency was, however, reported by Fransson et al. (7). They reported an incidence of 55–65% of loose or watery stools at Week 5 of treatment (64–76 Gy, 2 Gy/fraction). In another study, Tsai et al. (8) reported that hardly any increase in the incidence of diarrhea was seen during treatment (67 Gy, 1.8 Gy/fraction). The large variation in the reported frequencies can probably be explained by differences in the prescribed dose, treatment schemes (elective fields, margins), and definition of diarrhea used, as well as likely differences in data collection (e.g., with or without questionnaires, prospective or retrospective studies). In the present study, we investigated the hypothesis that because of a relatively large volume of the rectum visible on the planning CT scan, a clinically relevant systematic shift occurs in the position of the tumor during RT for a subgroup of patients. In such cases, tumor control could be affected when the applied margins are not sufficient to compensate for this effect. We analyzed the dose–response data from the Dutch multicenter randomized Phase III trial comparing 68 Gy with 78 Gy (9) to investigate this possible loss in tumor control.
Section snippets
Patient group
We analyzed the data from the Dutch Phase III trial randomizing between 68 Gy and 78 Gy. The main inclusion criteria were localized prostate cancer, Stage T1b-T4N0M0, no prior malignancies, and no previous RT of the pelvis. Patient recruitment took place between June 1997 and February 2003. We selected patients entered in the study at the Erasmus Medical Center - Daniel den Hoed Cancer Center (Rotterdam) or The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (Amsterdam) (n =
General statistics
In Table 2, the general statistics are summarized. The median follow-up was 51 months. The mean patient age was 69 ± 6.4 years. Treatment group 1 contained 18% of the patient population (n = 99); Group 2, 18% (n = 101); and Group 3/4, 64% (n = 349, 258 in Group 3, 91 in Group 4). The mean volume of the delineated anorectum (including filling) was 82.7 cm3, and the mean anorectal length (craniocaudal distance between the most upper and lower delineated slide) was 11.9 cm. The mean horizontal CSA
Discussion
We found evidence in our trial data that tumor control was significantly decreased in patients for whom the patient model for treatment planning was suspected to not be representative of the patient anatomy during the actual treatment owing to the large rectum visible on the planning CT scan.
This evidence was found for a subgroup of patients with an estimated SV involvement of ≥ 25% (Treatment group 3/4; that is, patients with Stage T2b-T4 and/or a combination of the risk factors of PSA level
Conclusion
Tumor control was significantly decreased in a subgroup of patients with a large rectum filling visible on the planning CT scan who were treated with conformal techniques and a 10-mm margin and who had an estimated risk of SV involvement of >25%. Current image protocols offer several solutions to further optimize the treatment. Additional research is needed to evaluate whether these localization techniques can prevent geometric misses.
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Supported by the Dutch Cancer Society (NKB Grants NKI 98-1830 and CKTO 96-10).
Conflict of interest: none.