Clinical Investigations
Association of prostate size with urinary morbidity following mixed conformal neutron and photon irradiation

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Abstract

Purpose: This study was designed to characterize the relationship between the observed rate of postradiation genitourinary (GU) complications and the prostate gland size.

Methods and Materials: Two hundred seventy-three patients received conformal neutron and photon irradiation to the prostate seminal vesicles. Data on post-treatment urinary morbidity were collected and examined in relationship to a number of clinical and technical factors.

Results: With a median follow-up of 30 months (range 7–61), the 4-year rate of Grade 2 or higher GU complications was 21%. On univariate analysis, the risk of complications was significantly associated with prostate size and neutron beam arrangement. On multivariate analysis, only the prostate size was significantly associated with the risk of GU morbidity. Patients with a preradiation prostate volume more than 74 cc had a two and a half fold increase in the risk of complications compared to patients with smaller glands.

Conclusion: Patients with an enlarged prostate have a significantly higher risk of chronic GU complications. Although these data were obtained for patients receiving combined neutron and photon irradiation, it is likely that these data would also be applicable for those patients receiving photon irradiation as well. These observations may add an additional rationale for the study of preirradiation hormonal treatment.

Introduction

Radiotherapy (RT) has undergone a technological revolution in the last 15 years. Computerized tomographic (CT) scan–based treatment planning has allowed for the development and widespread application of three-dimensional treatment planning (3D-CRT) 1, 2, 3, 4, 5. The data generated from these 3D-CRT systems include the dose and volume interrelationships of normal tissues as well as tumors 1, 6, 7. Thus, the dose of radiation delivered to all or part of an organ can now be precisely quantified and displayed.

In the treatment of prostate cancer, different combinations of radiation beams can be compared using these dose–volume histograms (DVH) to pick the “best” plan. Tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP) can be estimated for each treatment plan based on the information provided in these DVH (8). Thus, if the TCP and NTCP estimates are accurate, an “optimal” treatment plan can be generated for each patient.

Overall, the use of 3D-CRT has resulted in a reduction in the observed rate of acute and chronic complications, presumably secondary to reducing the volume of normal tissue irradiation 9, 10, 11, 12. This has allowed for investigation of radiation dose escalation programs in an attempt to improve the TCP 1, 7, 9, 10, 11. At Wayne State University, dose escalation has been accomplished through the use of conformal mixed photon and neutron irradiation (MNP) 13, 14. However, no correlation has been seen between the DVH for the bladder and rectum and the subsequent rate of chronic complications 15, 16. A complicated and labor-intensive analysis of the dose to the surface of the rectum and bladder suggests a correlation with morbidity, but this system is quite cumbersome and impractical for routine use (16).

A simple method of predicting and/or reducing morbidity is needed. Because the volume of the rectum and bladder receiving all or part of the radiation dose appears to be related to post-RT morbidity (6), and because this volume is directly related to the size of the target volume for RT, it is possible that reducing the size of the target may result in a reduction in toxicity. Preirradiation hormonal downsizing has been shown to reduce the prostate size, the volume of rectum and bladder receiving RT and to improve the predicted NTCP 17, 18. The volume of the prostate gland is a readily accessible parameter available in the majority of patients, and does not require a 3D system to calculate. This study was undertaken to identify if a correlation between the rate of post-RT complications and the pre-RT size of the prostate gland exists.

Section snippets

Methods and materials

Two hundred seventy-three patients treated between 1994 and 1997 for adenocarcinoma of the prostate were selected for this analysis. Patients were treated on 3 consecutive institutional review board–approved treatment protocols using conformal mixed neutron and photon irradiation. All patients selected for analysis had organ-confined disease (Stage T1 or T2) and completed irradiation more than 18 months before analysis in order to adequately assess the rate of chronic complications. Patient

Results

The median follow-up was 30 months (range 7 to 61 months). Forty patients (14%) had Grade 2 or higher GU complications. The 4-year actuarial rate of Grade 2 or higher GU complications was 21% (Fig. 1). There were 30 Grade 2, 9 Grade 3, and 1 Grade 4 complications.

The median prostate size was 52 cc (range 10 to 155 cc). African-American men had a significantly larger, average prostate volume of 64 vs. 53 cc, respectively (p = 0.0002). The patients with Stage T1 prostate cancer had larger

Discussion

The goal of planning radiation treatment for prostate cancer is to maximize the therapeutic ratio between local tumor eradication and chronic complications (21). Conformal treatment techniques based on CT-acquired anatomical data have done much to make these goals a reality 1, 4, 5, 7, 21. As a result of 3D-CRT, the risks of chronic complications have been reduced, modest dose-escalation has been safely accomplished, and the rates of tumor control have been enhanced 3, 9, 10, 11, 12. Dose and

Conclusions

In summary, patients with enlarged prostate glands have a two and a half fold increased risk of chronic GU complications. Based on these observations as well as the fact that hormonal therapy can reduce the volume of the prostate, it follows that preradiation hormones could be used in patients with enlarged prostate to make the treatment safer. While it is very likely that these data would also be applicable for patients receiving photon irradiation only, it is important to realize that these

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