Clinical Investigation
Predictive Factors and Management of Rectal Bleeding Side Effects Following Prostate Cancer Brachytherapy

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Purpose

To report on the incidence, nature, and management of rectal toxicities following individual or combination brachytherapy following treatment for prostate cancer over a 17-year period. We also report the patient and treatment factors predisposing to acute ≥grade 2 proctitis.

Methods and Materials

A total of 2752 patients were treated for prostate cancer between October 1990 and April 2007 with either low-dose-rate brachytherapy alone or in combination with androgen depletion therapy (ADT) or external beam radiation therapy (EBRT) and were followed for a median of 5.86 years (minimum 1.0 years; maximum 19.19 years). We investigated the 10-year incidence, nature, and treatment of acute and chronic rectal toxicities following BT. Using univariate, and multivariate analyses, we determined the treatment and comorbidity factors predisposing to rectal toxicities. We also outline the most common and effective management for these toxicities.

Results

Actuarial risk of ≥grade 2 rectal bleeding was 6.4%, though notably only 0.9% of all patients required medical intervention to manage this toxicity. The majority of rectal bleeding episodes (72%) occurred within the first 3 years following placement of BT seeds. Of the 27 patients requiring management for their rectal bleeding, 18 underwent formalin treatment and nine underwent cauterization. Post-hoc univariate statistical analysis revealed that coronary artery disease (CAD), biologically effective dose, rectal volume receiving 100% of the prescription dose (RV100), and treatment modality predict the likelihood of grade ≥2 rectal bleeding. Only CAD, treatment type, and RV100 fit a Cox regression multivariate model.

Conclusions

Low-dose-rate prostate brachytherapy is very well tolerated and rectal bleeding toxicities are either self-resolving or effectively managed by medical intervention. Treatment planning incorporating adjuvant ADT while minimizing RV100 has yielded the best toxicity-free survival following BT.

Introduction

Since its introduction to the clinic, low-dose-rate brachytherapy (BT) has been adopted as both a popular and efficacious treatment strategy for the management of localized prostate cancer (1). As the intraoperative placement of BT seeds has been refined, delivered radiation doses have increased, thus maximizing the therapeutic potential of BT (2). However, the escalation of local radiation doses has the potential to lead to chronic toxicities, especially within the context of combined modality therapies (CMT) that use supplemental external beam radiation therapy. One such toxicity, radiation proctitis, is due to the proximity of the posterior margin of the prostate to the anterior rectal wall and the inability to completely eliminate doses to this structure. Radiation proctitis has diverse clinical presentations typically including diarrhea, abdominal pain, constipation, and rectal bleeding (3).

In past work from our and other medical centers we have shown that the incidence of grade ≥2 proctitis can be limited by restricting the rectal volume receiving 100% of the prescription dose (RV100) to <1.3 mL 4, 5. Likewise, several groups have reported on the incidence of grade ≥2 proctitis following BT or CMT regimens, with incidence ranging from 1% to >9%, with much of the variability observed attributable to differences in treatment type and/or follow-up time (6). Yet, despite the widespread documentation of proctitis following the treatment of prostate cancer, few studies have reported on either grade ≥2 proctitis rates across multiple CMTs or the treatment of refractory rectal toxicities. In the present study, we therefore report a large (n=2572), retrospective analysis on the relationship between the nature, treatment, and predisposing factors contributing to the 10-year incidence of rectal morbidities following the treatment of localized prostate cancer using BT regimens.

Section snippets

Methods and Materials

All patients were treated for localized prostate cancer with low-dose-rate BT at Mount Sinai Hospital between October 1990 and April 2007. A total of 2752 patients were seen during this time frame with a median 5.86 years (minimum 1.0 years; maximum 19.19 years) follow-up time. The clinical characteristics of these patients are summarized in Table 1.

Upon evaluation of each patient's clinical history, tumor Gleason score, serum prostate-specific antigen (PSA), and T stage, patients were assigned

Results

The overall incidence of rectal morbidities following prostate cancer treatment is summarized in Table 3. The actuarial risk of developing grade 1 rectal bleeding was 20.57% (566 patients), whereas grade ≥2 bleeding/radiation proctitis was restricted to only 6.36% (175 patients) of the sample cohort (Fig. 1a). More severe treatment-related toxicities such as fistula formation or rectal ulceration were exceedingly rare, comprising only 9 (0.33%) cases. Moreover, most rectal morbidities were

Discussion

In this study, we have analyzed the incidence and factors predisposing to rectal toxicities following treatment of localized prostate cancer. We have shown that BT, either alone or combined with EBRT or ADT, is very well tolerated with actuarial risks of only 6.3% or 20.1% of patients developing primarily self-limiting grade ≥2 proctitis or grade 1 rectal bleeding, respectively. More severe rectal toxicities such as fistula (0.11%) or ulcer (0.22%) formation were especially rare and are in line

Acknowledgments

We thank Bruce Wunder and John Caligy for their help in maintaining our patient database and for assistance in statistical analysis.

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Conflict of interest: R.G.S. has received payments for speaking on behalf of the following companies: C.R. Bard, Inc, and Varian Medical Systems and N.N.S. has received payments for speaking on behalf of the following companies: Amgen Inc, Centocor Ortho Biotech Inc, and Ferring Pharmaceuticals. These relationships do not interfere with or influence the scientific goals or mission of this publication and these entities had no input into the current study.

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