Late rectal complications after prostate brachytherapy for localized prostate cancer

Incidence and management

Authors


Abstract

This review of the literature on late rectal complications after prostate brachytherapy indicated that it is a highly effective treatment modality for patients with clinically localized prostate cancer but can cause chronic radiation proctitis. The most common manifestation of chronic radiation proctitis was anterior rectal wall bleeding, which often occurred within the first 2 years after brachytherapy. It is interesting to note that the rates of late rectal morbidity appear to have declined over time, which may reflect improvements in implantation techniques and imaging. Rectal biopsy as part of the workup to evaluate rectal bleeding can lead to rectal fistula and the need for colostomy, a rare but major complication. The authors recommend 1) screening colonoscopy before brachytherapy for patients who have not had a screening colonoscopy within the preceding 3 years to rule out colorectal malignancies and, thus, facilitate conservative management should rectal bleeding occur; 2) lifestyle modifications during treatment to limit exposure of the rectum to radiation; and 3) conservative management for rectal bleeding that occurs within 2 years after brachytherapy. Cancer 2009. © 2009 American Cancer Society.

Prostate cancer is the leading cause of cancer in men and accounts for approximately 33% of cancer deaths among men in the US.1, 2 Management options for organ-confined, low- to intermediate-risk prostate cancer include watchful waiting, radical prostatectomy, external-beam radiation therapy, and prostate brachytherapy with permanent interstitial implants. Recent improvements in radioactive seed implantation techniques have established prostate brachytherapy as a highly effective treatment modality for localized prostate cancer, with long-term local and biochemical control similar to outcomes observed after radical prostatectomy and external-beam radiation therapy.3, 4 Because prostate cancer is diagnosed increasingly at early stages, when treatment tends to result in favorable survival outcomes, both patients and physicians are paying more attention to late morbidity and quality-of-life issues when choosing the primary treatment modality.

The reported benefits of prostate brachytherapy compared with radical prostatectomy and external-beam radiation therapy include lower rates of incontinence and lower rates of sexual dysfunction.5, 6 However, prostate brachytherapy can lead to chronic radiation proctitis, because the rectum, fixed in position and close to the prostate, often receives a large radiation dose with prostate brachytherapy (Fig. 1). The incidence of chronic radiation proctitis has increased over the past few years along with increased use of radiation therapy for the treatment of prostate cancer.7 The most common manifestation of radiation-induced rectal injury is rectal bleeding. Nonconservative management of rectal bleeding—for example, with argon plasma coagulation (APC) or rectal biopsy—may result in fistula development and the need for a colostomy.

Figure 1.

A typical 3-dimensional-rendered plan (lateral view) of a stranded seed implant. The close proximity of the anterior rectal makes it difficult to limit radiation dose to this area without compromising prostate dose coverage. Stranded seeds were used to maintain better seed spacing and alignment. SV indicates seminal vesicle; Gy, grays.

In this review, we summarize the clinical manifestations, incidence, and treatment of late rectal complications after prostate brachytherapy. Many patients who undergo prostate brachytherapy rely on their primary care physician, gastroenterologist, or colorectal surgeon for the management of late rectal complications after brachytherapy. The information provided in this article should help such clinicians provide patients with appropriate supportive care.

Clinical Manifestations of Chronic Radiation Proctitis

The effects of brachytherapy on the rectum can be classified as either acute or chronic. The 2 radioactive seeds commonly used for prostate brachytherapy are iodine 125 and palladium 103, which have half-lives of 60 days and 17 days, respectively. It is assumed that radioisotopes remain active for 5 half-lives after implantation.

Acute radiation proctitis occurs shortly after implantation and usually resolves within 6 months, during which time the radioactive seeds deliver the majority of the radiation. Acute radiation proctitis is characterized by diarrhea, intermittent rectal bleeding, abdominal pain, mucous discharge, and occasionally constipation. Of these symptoms, the most common is diarrhea, which affects from 50% to 75% of patients.8, 9 Examination by sigmoidoscopy often demonstrates inflammation, edema, and friable rectal mucosa. Pathologically, these changes usually are confined to the mucosa.10 In general, the clinical course is short, and symptoms improve with conservative measures, which are described in detail below.11, 12

In contrast to acute radiation proctitis, chronic radiation proctitis may take up to 2 years to develop and is not associated with the occurrence of acute proctitis.12, 13 Many studies define chronic radiation proctitis as persistent or new-onset rectal symptoms that occur from 6 months to 1 year after radioactive seed implantation.14-17 The common symptoms of chronic radiation proctitis are rectal urgency, incontinence, pain, strictures, mucous discharge, and rectal bleeding. Rarely, rectal fistula or perforation can occur, necessitating surgical intervention. The histologic changes associated with late rectal injury often include submucosal involvement in addition to changes in the mucosa, such as telangiectasia.10 A cardinal symptom of chronic radiation proctitis that distinguishes it from acute radiation proctitis is the presence of small-vessel vasculopathy. The resulting decrease in bowel vascularity and ischemia of the rectal wall increase the risk of mucosal ulceration and submucosal fibrosis.18 Along with focal mucosal ulceration, telangiectatic vessels represent a common source of rectal bleeding.

A rare but major late rectal complication of prostate brachytherapy is the development of rectal fistula. Rectal biopsy to evaluate rectal bleeding because of radiation proctitis appears to be an important factor in the development of rectal fistulas.19 In many instances, investigation of rectal bleeding prompts a screening colonoscopy with almost reflex-like biopsy of the radiation-scarred anterior rectal wall. Unlike nonirradiated rectum, the irradiated rectal wall, because of radiation-induced poor vascularity and fibrotic changes, demonstrates poor wound healing and is at high risk for fistula development (Fig. 2).

Figure 2.

This is an endoscopic image from a patient who had a rectal ulcer that was caused by chronic radiation proctitis.

Classification of Late Rectal Adverse Events

Most studies grade late rectal adverse events using the Radiation Therapy Oncology Group (RTOG) scoring criteria (Table 1) or a slightly modified version.16, 20 An alternative instrument for classifying rectal adverse events after prostate brachytherapy is the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) (CTCAE). The CTCAE leads to a more detailed classification of adverse events than the modified RTOG scale, further subdividing late rectal symptoms to include item-specific events, such as diarrhea, incontinence, urgency, proctitis, pain, spasms, and hemorrhage.21 Proponents of the CTCAE believe it yields a more comprehensive rectal toxicity profile that better captures the diverse and subtle rectal toxic effects of brachytherapy, which may not be appreciated adequately with the RTOG morbidity scoring criteria alone. By using the CTCAE late rectal toxicity reporting criteria, Shah and Ennis identified a novel rectal toxicity profile after brachytherapy in which most items had nontrivial (>5%) event rates after brachytherapy.21 The objective of a more specific rectal toxicity profile is to help physicians and patients make more informed management decisions after brachytherapy.

Table 1. Modified Radiation Therapy Oncology Group Rectal Toxicity Scale
  1. RTOG indicates Radiation Therapy Oncology Group.

Grade 1Mild and self-limitingMinimal, infrequent bleeding or clear mucous discharge, rectal discomfort not requiring analgesics, loose stools not requiring medications
Grade 2Managed conservatively, lifestyle (performance status) not affectedIntermittent rectal bleeding not requiring regular use of pads, erythema of rectal lining on proctoscopy, diarrhea requiring medications
Grade 3Severe, alters patient lifestyleRectal bleeding requiring regular use of pads and minor surgical intervention, rectal pain requiring narcotics, rectal ulceration
Grade 4Life-threatening and disablingBowel obstruction, fistula formation, bleeding requiring hospitalization, surgical intervention required

Incidence of Late Rectal Complications

Lower rates of rectal complications with improved brachytherapy techniques

Rectal outcomes have improved as implantation and planning techniques have been optimized and as experience with brachytherapy has grown. Until the late 1980s, brachytherapy was performed with an open laparotomy approach. The second generation was developed using a transperineal approach under ultrasound guidance, as described and pioneered in the US by Blasko et al.22, 23 Further generational improvements have emerged over the last decade with the use of ultrasound and computed tomography-based treatment planning systems and stranded seeds during implantation to improve seed placement and optimize dosimetry. This has led to a resurgence in the use of brachytherapy for localized prostate cancer, in which local control and biochemical outcomes are comparable to those observed with external-beam radiation therapy and radical prostatectomy.14, 24-27

In early published experiences, late rectal morbidity rates were relatively high.24, 28, 29 In the early experience of Wallner et al, the incidence of rectal ulceration approached 10%.24 This subsequently decreased to approximately 1% in their later reports, presumably as they gained experience.30 The incidence of rectal fistulas in other early series varied from <1% to 7%,24, 31-36 and the overall average incidence was 2.6%. In more contemporary series, the rates of rectal fistula have been between 0% and 1%.15, 37-39 The lower rates most likely are because of both technical improvements and a better understanding by nonbrachytherapists in managing postimplantation rectal bleeding.

Improvements in brachytherapy techniques also have lowered nonlife-threatening but more common rectal adverse events. In a large retrospective analysis of 248 patients who received prostate brachytherapy at a single institution and who were followed longitudinally from 1989 to 1996, the actuarial incidence of late grade 2 rectal bleeding was 9%.14 In a follow-up from the same institution of 367 patients with localized prostate cancer who received intraoperative brachytherapy from 1998 to 2006, the incidence of late rectal adverse events (defined as events present 1 year after implantation) was slightly lower, at 7%, 1%, and 0% for late grade 2, 3, and 4 rectal complications, respectively.15 Those authors attributed the reduction in late rectal complications to improved seed placement through the use of real-time intraoperative treatment planning.37 A Canadian group reported a 12-year brachytherapy experience using seeds with higher radioactivity. The rationale was to decrease trauma to the prostate by using a smaller number of needles. The grade 1 late rectal complication rate in that experience was 4.2%, and there were no grade 2 or greater complications.39 Our institution recently reported results using stranded-seed implants, a technique that decreases the amount of radioactivity to the prostate gland, thereby improving implant efficiency.40 By using a validated quality-of-life instrument, we observed less rectal toxicity when the rectal volume that received 100% of the prescribed dose was limited to <1 mL.

However, not all novel approaches have led to improved rectal toxicity outcomes. Using magnetic resonance imaging-based guidance with intraoperative planning, Albert et al observed higher than expected incidences of grade 1, 2, and 3 rectal complications (80%, 18%, and 8%, respectively) after monotherapy.41 Their findings underscore the importance of operator and institutional experience when brachytherapy is used for the treatment of localized prostate cancer. Many of the promising results with newer techniques were obtained at centers of excellence, and whether they can be generalized to the brachytherapy community at large remains uncertain. A population-based, random-sample study most likely will be required to answer this question.

Incidence of rectal bleeding in contemporary studies

Table 2 summarizes the results of contemporary studies that examined the incidence of late rectal complications after prostate brachytherapy. It should be emphasized that the lack of uniform reporting criteria make it difficult to directly compare the rates of late rectal complications after brachytherapy.

Table 2. Reported Series of Late Rectal Adverse Events After Prostate Brachytherapy
StudyNo. of PatientsYear(s)Median Follow-Up, moHormones, %EBRT, %AE Criteria5-Year Actuarial Incidence of Late Rectal Toxicity, %
Grade 2Grade 3Grade 4
  1. EBRT indicates external beam radiation therapy; AE, adverse events; RTOG, Radiation Therapy Oncology Group; NCI CTCAE, National Cancer Institute Common Toxicity Criteria for Adverse Events; NR, not reported.

Phan 2008382631998-200668550Modified RTOG3.70.40
Zelefsky 2007375621998-200440310NCI CTCAE61NR
Zelefsky 2007153671998-200263350NCI CTCAE710.3
Martin 2007393961994-200160650Modified RTOG<100
Albert 2003412011997-200234NR33Modified RTOG188NR
Waterman & Dicker 200317981997-19993200Modified RTOG9.8<10
Zelefsky 2000142481989-199648NRNRModified RTOG900.4
Gelblum & Potters 2000168251992-199848NR17Modified RTOG6.60.5NR

In general, the rates of late rectal complications that could be managed with conservative therapy (grade 2) ranged from 3.7% to 18%, whereas the rates of persistent or severe rectal bleeding that required more aggressive surgical or procedural interventions (grade 3 and 4) were in the <1% to 8% range. These complication rates in contemporary series were lower than the rates in early reports on rectal complications, which typically ranged from 6% to 21%.9, 24, 28, 29 At our institution, the 5-year rates of rectal complications among 263 patients who received prostate brachytherapy since 1998 were encouraging (grade 1, 12.8%; grade 2, 3.7%; grade 3, 0.4%; and grade 4, 0%) (Fig. 3). Rectal bleeding accounted for the majority of late gastrointestinal complications, and approximately 80% of all episodes of rectal bleeding occurred within the first 2 years after implantation.38

Figure 3.

This chart illustrates long-term rectal complication rates for patients with localized prostate cancer treated with permanent interstitial seed implantation from 1998 to 2006 at The University of Texas M. D. Anderson Cancer Center.

Our finding that the majority of late rectal complications can be managed successfully with conservative therapy agree with those reported by other investigators in large series. In a series of retrospective analyses, Zelefsky et al observed that the actuarial incidence of late grade 2 rectal bleeding was 6% to 9% and that the incidence of late grade 3 rectal bleeding was 0.4% to 1%.14, 15, 37 Gelblum and Potters reported a similar difference in the incidence of grade 2 and 3 late rectal complications in a series of 825 patients who received prostate brachytherapy alone: The actuarial incidence of grade 2 and 3 rectal complications was 6.6% and 0.4%, respectively.16 Waterman and Dicker and Snyder et al reported rates of grade 2 late rectal complications of 9.8% and 10.4%, respectively.17, 42 Together, these findings indicate that, for brachytherapy performed using an ultrasound-guided, transperineal approach, the incidence of chronic radiation proctitis requiring medical management ranges between 3.7% to 10.4%, and the incidence of chronic radiation proctitis requiring endoscopic therapy is <1%.

Similarly, our finding that late rectal complications tend to occur within the first 2 years after implantation agrees with findings from other studies. For example, Snyder et al and Kaye et al reported no episodes of chronic radiation proctitis after the third year postimplantation.42, 43 Gelblum and Potters reported a peak incidence (9.5%) of rectal complications at 8 months after implantation, and no patients had rectal symptoms at 42 months.16 Snyder et al observed an increased incidence of radiation proctitis the first year after implantation; 14% of their patients developed symptoms in the first year, and 72% had symptoms in the second year, whereas the majority reported symptom resolution after the third year.42 Likewise, Hu and Wallner observed that no patients developed rectal bleeding after 28 months.28

There is a consensus in the prostate brachytherapy community that the probability of developing radiation proctitis increases with higher radiation dose to the rectal wall. Thus, the goal of improving tumor control with higher doses must be balanced against the corresponding increased risk of complications. Advances in implantation and planning techniques, including higher quality imaging and more meticulous approaches, have been pursued to enhance this therapeutic ratio. Results of the aforementioned large, single- and multi-institutional, retrospective studies performed over the past 15 years appear to indicate that these efforts at improved quality are paying off.

Management of Rectal Bleeding Caused by Chronic Radiation Proctitis

The objectives of treating radiation-induced rectal bleeding are to control bleeding and to improve the patient's quality of life by reducing the need for hospital or office visits, blood transfusions, and symptoms associated with anemia or rectal bleeding. There is no consensus regarding the preferred treatment for rectal bleeding. The 3 general categories of commonly used interventions are medical, endoscopic, and surgical management (Table 3).

Table 3. General Treatments for Chronic Radiation Proctitis
Type of TherapyProposed MechanismSummary
  1. HBOT indicates hyperbaric oxygen therapy; Nd:YAG, neodymium/yttrium aluminum garnet argon; KTP, potassium titanyl phosphate; APC, argon plasma coagulation.

Medical therapies Historically used as first-line therapy with mixed results; few randomized trials available; HBOT appears to be effective
 5-Aminosalicylic acidAnti-inflammatory
 SucralfateAnti-inflammatory
 Steroid enemasAnti-inflammatory
 Short-chain fatty  acid enemasPromote healing
 HBOTPromote healing
Endoscopic therapies More effective than medical therapies but associated with higher rectal complication rate; APC is preferred over laser coagulation
 Topical formalinChemical cauterization
 Heater and bipolar cauteryThermoelectric cauterization
 Nd:YAG and KTP laserNoncontact electrocoagulation
 Argon plasma coagulationNoncontact electrocoagulation
Surgical therapies High risk of postoperative morbidity, reserved for severe rectal strictures and rectal fistulas
 Proctectomy 
 Diverting colostomy 
Table 4. Literature Review of Endoscopic Therapies
TherapyNo. of StudiesResultsNo. of Sessions NeededComplicationsStudy(s)
  1. PR indicates partial response; Nd:YAG, neodymium/yttrium aluminum garnet argon; KTP, potassium titanyl phosphate.

Topical formalin5Initial response rate, 59%-100%; PR rate at 1 y, 19%-38%1-3Rectal strictures, <1%; perianal ulcers fissures, 5%Wilson & Rex 2006,65 Mathai & Seow-Chen 1995,67 Seow-Chen 1993,68 Saclarides 1996,69 Biswal 1995,70 Counter 1999,71 Roche 1996,72 Yegappan 199873
Heater and bipolar probe2Response rate, 100%1-4NoneFuentes 1993,75 Davila 199676
Nd:YAG and KTP laser5Response rate at 1-3 y, 75%-90%2-5Ileus, pain, 1%-5%; rectal fistula, <1%Taylor 1993,78 Buchi 1991,80 Buchi & Dixon 1987,82 Chapuis 1996,83 Taylor 200084
Argon plasma coagulation5Response rate at 1-2 y, 90%-100%2-3Rectal strictures, 2%Tam 2000,88 Silva 1999,89 Fantin 1999,90 Sebastian 2004,91 Rotondano 200393

The majority of articles published on medical therapies for postradiation rectal bleeding are case reports or case series; only a few randomized trials have been performed.7, 11 In addition, the methods used to grade initial symptom severity or responses to therapy are not consistent. Because of these limitations, the management of rectal bleeding largely remains empirical. The evidence suggests a better outcome but a higher risk of additional rectal complications with endoscopic techniques than with medical therapies. For these reasons, medical therapies have fallen out of favor in recent years. APC represents a safer and, thus, more popular endoscopic technique for controlling rectal bleeding, but caution still is required with this technique, because it can result in iatrogenic rectal injury. Surgical interventions should be used only as a last resort, because they are associated with increased morbidity. The following is a brief summary of therapies available for the treatment of postirradiation rectal bleeding that have been described in the literature.

Medical therapies

Historically, medical therapies—including aminosalicylates, sucralfate, steroid enemas, and short-chain fatty acid enemas—were used as first-line therapy to treat rectal bleeding.

5-Aminosalicylic acid

5-Aminosalicylic acid (5-ASA) is the active component of sulfasalazine, an aminosalicylate that is an established and well tolerated pharmacologic agent for the treatment of inflammatory bowel disease.44 The anti-inflammatory actions of 5-ASA occur through a variety of mechanisms, most notably reduction of prostaglandin production.45, 46 Initially, it was believed that 5-ASA would be an effective medical agent for the treatment of chronic radiation proctitis.45 However, several small trials of 5-ASA for radiation proctitis have produced mixed results—some produced symptomatic improvement or no clinical changes, whereas others produced worsening of clinical symptoms.47-50

Sucralfate

Sucralfate is an aluminum salt that adheres to mucosal cells and stimulates prostaglandin production, producing cytoprotective effects, and has been used in the treatment of peptic ulcers.7 Sucralfate is administered orally and by suspension enema. Studies by Sasai et al demonstrated clinical and endoscopic improvement in 3 patients who received oral sucralfate.51 In a larger open-label trial of 26 patients, the use of sucralfate suspension enemas achieved symptom resolution in 75% of patients in 45 months.52 These open-label trials suggest that sucralfate may be effective in the treatment of radiation proctitis, although placebo-controlled, randomized trials are needed to fully assess efficacy.

Steroid enemas

Corticosteroids exert their anti-inflammatory effects in part by inhibiting histamine release and thereby stabilizing mast cells. It is anticipated that corticosteroids will help alleviate the symptoms of radiation proctitis. In 1 of the few published prospective, randomized, double-blind trials, Kochhar et al compared oral sulfasalazine plus prednisone enemas with sucralfate enemas in 30 patients who had radiation-induced rectal bleeding.45 Sucralfate enemas produced superior clinical results and were cheaper and better tolerated, although both treatments did produce beneficial effects.

Short-chain fatty acid enemas

Short-chain fatty acids (SCFAs) are bacterial byproducts of carbohydrate metabolism in the colon and are used by the colonic mucosa as an important source of oxidative energy. The dependence of the colonic mucosa on SCFAs, butyrate in particular, increases toward the rectum.53 Several studies of SCFA enemas to promote healing of postradiation mucosal lesions have yielded conflicting results. Initial studies indicated a decrease in rectal bleeding and endoscopic improvements with SCFA use,54-56 but those findings were not reproduced in a subsequent prospective, randomized, double-blind study.57, 58

Hyperbaric oxygen therapy

The use of hyperbaric oxygen has proved moderately successful in the treatment of rectal bleeding. A report by Warren et al indicated that 9 of 14 patients with chronic radiation proctitis experienced resolution of symptoms after therapy.59 Similarly, a retrospective review by Woo et al revealed that hyperbaric oxygen therapy resulted in partial or complete symptomatic response in >50% of patients with chronic radiation proctitis.59, 60 A recent randomized, double-blind, crossover trial demonstrated clinical improvement 3 years after therapy with an absolute risk reduction of 32% between treated and untreated patients.61 Limitations for its wider use include the high expense and the requirement of >20 sessions to achieve noticeable results.

Surgical therapies

The most common indications for surgical intervention in the treatment of rectal bleeding because of chronic radiation proctitis are rectal strictures and fistulas. Surgical treatment options include excision, diversion (diverting stoma), and reconstruction.62 Historically, the postoperative outcomes are poor—rates of postoperative complications such as sepsis, wound dehiscence, bowel obstruction, and de novo rectal fistula range from 15% to 79%.9, 11 In 1 series, the reported postoperative mortality rate was >50%.63 Recent postoperative results have been more encouraging (mortality rate, 3%; morbidity rate, 9%) because of better patient selection for surgery.11

Endoscopic therapies

Persistent or moderately severe rectal bleeding caused by radiation proctitis, as discussed above, appears to be most amenable to endoscopic therapies (Table 4), which have been proven to reduce symptoms associated with anemia and the frequency of hematochezia. Even with endoscopic approaches, however, there remains a risk of rectal ulceration or fistula, and this risk increases when larger radiation ulcers are treated. Thus, endoscopic therapy to control rectal bleeding should be done only by experienced gastroenterologists with particular awareness of postradiation rectal injury.

Early endoscopic approaches included delivery of topical formalin through a rigid scope and electrocauterization through the use of heater probes or bipolar probes. These early approaches were followed by the development of laser techniques using the neodymium/yttrium aluminum garnet (Nd:YAG), argon, and potassium titanyl phosphate (KTP) lasers. The use of APC represents a newer, safer, less expensive, and more widely available technique that has become an attractive treatment option for rectal bleeding that is refractory to medical management.

Topical formalin

Formalin, a mixture of methanol and formaldehyde, was used initially to treat radiation-induced cystitis before it was applied to treat radiation proctitis.64, 65 The technique involves the direct application of 4% formalin to the affected area using a rigid proctoscope with either a formalin-soaked gauze or by direct instillation to induce chemical cauterization of telangiectatic mucosal vessels.11, 64 In several small, nonrandomized studies, the short-term success rate of this technique ranged from 60% to 100%.66-73 The documented complications, including perianal ulcerations and fissures, anal stenosis, and fecal incontinence, occurred in 27% of patients.64

Heater and bipolar probes

For many years, the use of heater probes or bipolar probes was the preferred endoscopic method for controlling postradiation rectal bleeding. Both techniques are more effective than medical therapy alone and produce reductions in both the frequency and the severity of rectal bleeding.65, 74 Both types of devices can be used in patients who have active bleeding, because they work by direct contact (noncontact probes can produce charring of blood when there is active bleeding). Heater probes are used to apply heat directly and reach temperatures up to 250 degrees Fahrenheit, whereas bipolar probes use electricity to coagulate tissues and do not exceed 100 degrees Fahrenheit. The 2 types of probes appear to produce equally good results (100% response with both treatments) and no complications.74, 75 The heater and bipolar probes largely have been replaced by more advanced laser and argon plasma technology, although this was not based entirely on better evidence of efficacy or safety.

Laser

Several different laser systems, including the Nd:YAG, argon, and KTP lasers, have been used for the treatment of postradiation rectal bleeding. The Nd:YAG laser was among the first endoscopic approaches used and demonstrated good short-term effectiveness.7 However, its higher depth of penetration (5 mm) and the need to aim directly at telangiectasias increased the risk of bowel damage, limiting the use of this technique. In contrast to the Nd:YAG laser, the argon and KTP lasers have a lower depth of penetration (1-2 mm) and, thus, are useful for the treatment of superficial vascular lesions and are associated with a lower risk of bowel perforation.

Published data indicate that both the Nd:YAG laser and the argon laser are effective in the short term for treating rectal bleeding.76-83 Data on use of the KTP laser for radiation proctitis still are limited, although, in 1 study, 65% of patients reported symptom improvement after 2 sessions.84 Overall, approximately 80% to 88% of patients have marked reduction in daily rectal bleeding after a median of 3 sessions of laser treatment. In the study that had the longest term follow-up, Taylor et al reported that 70% of patients required additional treatment sessions for recurrent bleeding after the initial sessions resulted in cessation of bleeding.78 Major disadvantages of laser therapy are its high cost, limited availability, and associated risk of bowel perforation. Rates of complications of Nd:YAG laser treatment, including rectal wall ulceration and fistula development, reportedly range between 1% and 6%.77 The argon and KTP lasers theoretically should have better safety profiles, although direct comparative studies have not been performed to date.

Argon plasma coagulation

APC represents a safer, less expensive, and more widely available alternative to laser therapy that has gained popularity since its initial use with a flexible endoscope in 1994. APC uses a high-frequency, monopolar, electrosurgical generator, a source of inert argon gas as a conducting medium, and is delivered through a through-the-scope catheter.85 APC is a noncontact method of electrocautery in which monopolar current travels directly from the single electrode to the tissue. This has the advantage of causing less charring of tissue and a more predictable depth of penetration. Villavicencio et al demonstrated the successful short-term resolution of rectal bleeding after APC treatment in >90% of patients who previously had not responded to medical or other endoscopic therapies.86 In several other studies, cessation of bleeding was reported after 1 to 3 sessions of APC.87-92 Complications of APC include rectal pain, rectal stenosis, altered bowel habits, and rectal wall injury. Reported rates of rectal ulceration leading to fistula development range from <1% to 2%.93, 94 Although the risk of rectal injury is lower with APC than with traditional laser therapy, rectal injury still can occur, especially with excessive rectal wall painting of diffuse radiation-induced lesions or prolonged or repeated cautery to the same area.

Recommendations

For the treatment of rectal bleeding after implantation, we recommend conservative management with oral and rectal steroids as well as rectal sucralfate. In cases of significant or persistent rectal bleeding, topical 4% formalin may be used. APC, although it is more effective than medical therapy in controlling rectal bleeding, should be done only by gastroenterologists with experience in treating patients who have undergone irradiation and needs to be performed cautiously in patients who have larger radiation ulcers.

In some patients, persistent rectal bleeding may elicit concerns regarding colorectal malignancy, especially in those who have undergone previous pelvic irradiation. Baxter et al observed that the incidence of carcinoma increased significantly between Year 5 and Year 15 after prostate radiation therapy and that the incidence doubled from 0.5% to 1% between Year 5 and Year 10.95 In our experience, rectal bleeding caused by radiation proctitis after prostate brachytherapy usually occurs within 2 to 3 years after implantation. Thus, rectal bleeding within 3 years after implantation is more likely caused by radiation proctitis than by colorectal malignancy. A screening colonoscopy is recommended within 3 years before an implant to rule out any potential malignancies that may develop within 2 to 3 years after treatment and to facilitate conservative management in the event rectal bleeding occurs. However, if there are concerns regarding carcinoma in patients who have a significant history of polyps, then a colonoscopy often is performed.

Several studies have demonstrated a close association between anterior rectal wall biopsy and delayed healing/eventual rectal fistula formation in patients who have previously received radiation therapy for prostate cancer.16, 19 In a study of 503 patients who received prostate seed implants, Tran et al reported that 0.4% of patients developed rectal fistulas, and all of those patients had undergone extensive intervention that included anterior wall biopsy for rectal bleeding.96 Theodorescu et al evaluated 765 patients who received brachytherapy between 1994 and 1999.19 Seven of those patients (0.9%) developed rectal fistulas between 9 and 12 months after implantation. Upon closer inspection of the data, the authors observed a strong association between rectal fistula formation and anterior rectal biopsy performed to evaluate rectal bleeding after implantation. In none of the patients did rectal biopsy reveal information other than the presence of chronic radiation effects. We recommend avoiding rectal wall biopsy for the investigation of rectal bleeding after prostate brachytherapy unless cancer is strongly suspected. A more prudent approach would be to perform a screening colonoscopy before implantation to facilitate conservative management if rectal bleeding occurs.

In conclusion, to minimize the risk of developing a nonhealing ulcer and subsequent fistula on the anterior rectal wall, we recommend 1) screening colonoscopy before brachytherapy for patients who have not had a screening colonoscopy within the preceding 3 years to rule out colorectal malignancies and, thus, facilitate conservative management should rectal bleeding occur; 2) lifestyle modifications, such as modifying diet to limit gas expansion of the rectum, limiting the duration of daily bicycle exercise, and, during treatment, limiting exposure of the rectum to radiation; and 3) conservative management for rectal bleeding and symptoms associated with chronic radiation proctitis that occurs within 2 years after brachytherapy.

Acknowledgements

We thank Stephanie Deming for her assistance in the editing and preparation of the article.

Conflict of Interest Disclosures

The authors made no disclosures.

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