Clinical investigations
Prostate
Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: Findings from a prospective, multi-institutional, phase I/II dose-escalation study

https://doi.org/10.1016/j.ijrobp.2004.05.026Get rights and content

Purpose

To assess the relationship between the dose to the bulb of the penis and the risk of impotence in men treated on Radiation Therapy Oncology Group (RTOG) 9406.

Methods and materials

Men enrolled on a Phase I/II dose-escalation study, RTOG 9406, who were reported to be potent at entry and evaluable (n = 158) were selected for inclusion. Follow-up evaluations were scheduled every 3, 4, and 6 months for the first, second, and the third through fifth years, then annually. At each follow-up visit an assessment of potency status was made. Penile structures were defined by a single observer blinded to the potency status, using Web-based, on-line software. The dosimetry for penile structures was calculated at the Quality Assurance Center at Washington University and provided to RTOG Statistical Headquarters to determine whether there was a relationship between dose and impotence.

Results

Patients whose median penile dose was ≥52.5 Gy had a greater risk of impotence compared with those receiving <52.5 Gy (p = 0.039). In a multivariate analysis neither age, the dose to the prostate, nor the use of hormonal therapy correlated with the risk of impotence.

Conclusions

Dose to the bulb of the penis seems to be associated with the risk of radiation-induced impotence.

Introduction

Among the many controversial issues surrounding the treatment of clinical localized prostate cancer is the impact of various treatment options on sexual function. Although most comparative studies give an edge to radiotherapy in terms of the likelihood of preserving sexual function compared with surgery, not all studies are in agreement on this matter (1, 2). Complicating this issue is the fact that most studies reported to date have had short follow-up, are retrospective in nature, and are based on patients treated with older techniques to lower doses of radiation. The shortcomings of these studies are particularly relevant given the fact that numerous recent studies have demonstrated that higher doses result in a reduction in the risk of recurring after radiotherapy (3, 4, 5). The higher doses used in these series might be expected to compromise sexual function because in general, radiation-induced complications depend primarily on dose. Might the use of higher doses cause impotence to be an unavoidable consequence of curative radiotherapy?

Radiation Therapy Oncology Group (RTOG) 9406 is a landmark, multi-institutional Phase I/II study that set out to demonstrate that patients could be safely treated to higher-than-conventional doses with three-dimensional conformal radiotherapy (3D-CRT). Thus far, we have shown that late Grade 3 toxicity can be substantially reduced compared with historic controls (6, 7, 8). However, we have not previously reported on the impact of dose escalation on sexual function. To our knowledge, this represents the first large, prospective, multicenter study to assess the impact of increased doses of radiotherapy guided by 3D conformal planning software on sexual function.

Several recent retrospective studies suggest that the dose of radiation to the proximal penis might be a predictor of radiation-induced impotence (9, 10). This finding is not surprising, given that all other radiation-associated late normal tissue complications are related to dose and volume. RTOG 9406 provides an opportunity to clarify whether radiation-induced impotence is an unavoidable consequence of dose escalation or an avoidable, technique-dependent complication. Could awareness of this dose–volume relationship allow radiation oncologist to reduce the risk of impotence despite delivering high-dose radiation to the prostate?

Section snippets

Methods and materials

In 1994, the National Cancer Institute initially funded nine institutions with 3D-CRT capabilities to determine the feasibility of conducting a large dose-escalation study in men with localized prostate cancer. After 1995, the protocol was opened to other qualifying RTOG institutions. Each participating institution was required to provide details of their 3D-CRT treatment-planning systems and demonstrate their ability to exchange protocol-compliant treatment-planning data electronically with

Results

One hundred and fifty-eight patients were identified who were recorded as being potent at registration and evaluable for potency status with subsequent follow-up. The median age of these patients was 68 years (range, 42–79 years). The disease group distribution was 46%, 40%, and 14% for disease groups 1, 2, and 3, respectively. The distribution of dose level for primary tumor was 31% at 68.4 Gy and 69% at 73.8 Gy. There was no association between age and potency or between disease group and

Discussion

At the time that RTOG 9406 was started, it was common to place the inferior border of the radiation field at the lower border of the ischial tuberosities (15). When this is done, much of the penis is incidentally included within the radiation field. One study demonstrated that “locating the inferior border of the external beam fields at the ischial tuberosity adequately treats at least 95.4% of all prostate patients with a margin of 1.5 centimeters or more below the prostate apex,” arguing for

References (26)

Cited by (0)

Supported by grants RTOG U10CA 215661, CCOP U10CA37422, and Stat U10CA 32115 from the National Cancer Institute.

View full text