Patient Selection for Prostate Brachytherapy: More Myth Than Fact: Review 1

The role of prostate brachytherapy in the treatment of prostate cancer continues to expand and evolve. The increasing clinical use and wider acceptance of this treatment modality can be attributed to published 10-year data demonstrating cure rates equivalent to those of radical prostatectomy and to quality-of-life studies that demonstrate relatively lower morbidity from brachytherapy compared to surgery.[1-4] It is the ease and convenience of treatment, the apparent equivalent cure rates, and the perception of lower morbidity that makes this treatment so appealing to patients. However, like all treatments, prostate brachytherapy does have side effects, and some patients will suffer significant complications or severe morbidity.

Considerable effort has been expended over the past 10 years attempting to identify risk factors that predict for excessive brachytherapy-related morbidity so that such therapy can be avoided in the high-risk patient. In the accompanying article, Merrick, Wallner, and Butler explore a variety of commonly cited risk factors reported to be associated with poor outcomes or excessive morbidity following brachytherapy. They rely heavily on their own admirable work in this area to reach conclusions. Their approach to analysis compartmentalizes individual risk factors and presents each in black-and-white terms as either a contraindication or not a contraindication. Unfortunately, this approach oversimplifies the consideration that the thoughtful physician should give to some of these issues when counseling patients and recommending treatment.

Gray Areas
The authors state that large prostate glands can be implanted with acceptable morbidity and adequate dosimetric quality, dismissing the commonly quoted upper limit of 50 or 60 cm3. However, they do not define for us what they consider "acceptable morbidity." A number of publications confirm that the risk of acute urinary retention increases significantly as prostate size increases.[5-7] Although the majority of these patients will not experience protracted urinary retention or long-term urinary dysfunction, it is clear that the risk of requiring at least short-term catheterization is increased in patients with large prostates. Whether this risk qualifies as a contraindication is in the eye of the beholder. Regardless, it would be a disservice not to inform our patients about this increased risk.

Individual issues of prostate anatomy and urinary function such as prostate size, transitional zone volume, International Prostate Symptom Score (IPSS), and median lobe hyperplasia are dissected by the authors and related to outcomes. However, these issues are all interrelated under the collective problem of benign prostatic hypertrophy (BPH) and lower urinary tract symptoms. For example, it is hard to imagine a large prostate not having a large transitional zone, and large transitional zones and/or median lobe hyperplasia commonly result in increased lower urinary tract symptoms with consequent elevation of the IPSS. It is likely that the picture is incomplete and that more sophisticated evaluation of multifactorial BPHrelated issues may eventually clarify the potential hazard more accurately.

Pubic Arch Interference
The problem of pubic arch interference is dismissed as an insignificant problem easily surmounted by either needle or patient manipulation. Although it is true that prostate volume alone does not predict pubic arch interference well, review of the quoted Bellon et al study[8] reveals that nearly all patients with prostates over 60 cm³ had some degree of arch interference, while those smaller than 60 cm³ may or may not demonstrate interference. It is possible for the experienced and skilled brachytherapist to overcome arch interference by needle angulation techniques and achieve satisfactory seed placement. Can the less experienced do the same?

Peschel et al[9] found that larger gland size was associated with a greater degree of pubic arch interference that required some modification of needle placement. The minimum tumor dose was lower in some patients that required the modified needle placement. Although cancer risk factors were equal in both groups, the 4-year biochemical disease-free rate was only 38% for patients with pubic arch interference, compared to 73% for those with no interference. Thus, the average practitioner may not posses the degree of skill necessary to accurately place seeds in the face of arch interference and would be on safer ground cytoreducing a large prostate than cavalierly attempting to manipulate needles.

Other Considerations
In their discussion of the impact of comorbidities and isotope choice on outcomes, the authors provide an excellent and accurate summary that is useful in the counseling of patients.

An important issue facing brachytherapists is the significance of adverse prognostic factors and the use of supplemental external-beam radiotherapy (EBRT) and/or androgen deprivation with brachytherapy. The authors correctly point out that brachytherapy is capable of delivering more intraprostatic radiation than any other existing radiotherapeutic approach and that a well-performed implant should be capable of achieving a cancer-ablative dose at least 5 mm beyond the prostate capsule. These characteristics may well obviate the negative impact of adverse pathologic features that has been demonstrated with radical prostatectomy or definitive EBRT, but more data are necessary.

There is also the question of the brachytherapist's skill in achieving not only complete gland coverage but also generous margins for these more advanced malignancies without overdosing the rectum or bladder neck. Those who do not possess this level of expertise might be well advised to select favorable patients for brachytherapy monotherapy and use combination therapy in those with more advanced disease. However, it is becoming clear that the addition of EBRT to brachytherapy increases rectal toxicity and reduces potency. This increased morbidity coupled with the lack of demonstrable improvement in biochemical outcomes to date in experienced centers makes the routine use of supplemental external radiation questionable.[10] An important Radiation Therapy Oncology Group trial comparing brachytherapy alone to brachytherapy plus EBRT in intermediate-risk patients is under way and should clarify this issue.

Conclusions
Brachytherapy is an important part of the prostate cancer treatment armamentarium and should be an option for most patients with clinically localized disease. When counseling patients, the physician should realistically assess his own experience and skill level relative to the technical challenges presented by an individual patient. The patient should be honestly informed regarding the potential for both short- and long-term morbidity before he commits to this treatment. "Contraindications" then become a sliding scale dependent on physician experience and patient desires. In this way, patients will continue to be well served by brachytherapy.

References:

1.

Talcott JA, Manola J, Clark JA, et al: Timecourse and predictors of symptoms after primaryprostate cancer therapy. J Clin Oncol21:3979-3986, 2003.

2.

Sylvester JE, Blasko JC, Grimm PD, etal: Ten-year biochemical relapse-free survivalafter external beam radiation and brachytherapyfor localized prostate cancer: The Seattle ex-perience. Int J Radiat Oncol Biol Phys 57:944-952, 2003.

3.

Grimm PD, Blasko JC, Sylvester JE, etal: 10-year biochemical (prostate-specific antigen)control of prostate cancer with 125-Ibrachytherapy. Int J Radiat Oncol Biol Phys51:31-40, 2001.

4.

Potters L, Huang D, Calugaru E, et al:Importance of implant dosimetry for patientsundergoing prostate brachytherapy. Urology62:1073-1077, 2003.

5.

Crook J, McLean M, Catton C, et al: Factorsinfluencing risk of acute urinary retentionafter TRUS-guided permanent prostate seedimplantation. Int J Radiat Oncol Biol Phys52:435-460, 2002.

6.

Friedland JL, Tsao A, Pow-sang JM, et al:Urinary retention following prostate brachytherapy.J Brachytherapy Intl 17:48-51, 2001.

7.

Terk MD, Stock RG, Stone NN, et al:Identification of patients at increased risk forprolonged urinary retention following radioactiveseed implantation of the prostate. J Urol160:1379-1382, 1998.

8.

Bellon J, Wallner K, Ellis W, et al: Use ofpelvic CT scanning to evaluate pubic archinterference of transperineal prostatebrachytherapy. Int J Radiat Oncol Biol Phys43:579-581, 1999.

9.

Peschel RE, King CR, Roberts K: Pubicarch interference in permanent prostate implantpatients. J Brachytherapy Intl 14:241-248,1998.

10.

Blasko JC, Grimm PD, Sylvester JE,et al: The role of external beam radiotherapywith I-125/Pd-103 brachytherapy for prostatecarcinoma. Radiother Oncol 57:273-278,2000.