| MP 8.01.14 | Brachytherapy for Clinically Localized Prostate Cancer Using Permanently Implanted Seeds | |
| Medical Policy | ||
| Section Therapy |
Original Policy Date 7/31/97 |
Last Review Status/Date Revised with literature search/5:2009 |
| Issue 5:2009 |
Return to Medical Policy Index |
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Description
Brachytherapy is a procedure in which a radioactive source (e.g., radioisotope 'seeds') is used to treat localized prostate cancer. With brachytherapy, the radiation penetrates only short distances; this procedure is intended to deliver tumoricidal radioactivity directly to the tumor and improve local control, while sparing surrounding normal tissue. Local tumor control has been reported to be associated with lower distant metastasis rates and improved patient survival. Seeds can be permanently or temporarily implanted. Permanent (low-dose rate, LDR) brachytherapy is generally used for those with low-risk disease; temporary (high-dose rate, HDR) brachytherapy is typically reserved for intermediate- or high-risk patients. This policy reviews permanent brachytherapy in prostate cancer.
The proposed biologic advantages of brachytherapy compared to external beam radiation therapy (EBRT) are related to the dose delivered to the target and the dose-delivery rate. The dose rate of brachytherapy sources is generally in the range of 40-60 centrigray per hour, whereas conventional fractionated EBRT dose rates exceed 200 centigray per minute. Enhanced normal tissue repair occurs at the lower dose rates. Repair of tumor cells does not occur as quickly, and these cells continue to die during continued exposure. Thus, from a radiobiological perspective, low-dose rates cause ongoing tumor destruction in the setting of normal tissue repair. In addition, brachytherapy is performed as a single procedure in the outpatient setting, which may represent a patient preference issue compared to the multiple sessions required to deliver EBRT. The total doses of radiation therapy that can be delivered may also vary between EBRT and brachytherapy, especially with newer forms of EBRT such as 3D conformal radiation therapy and intensity modulated radiation therapy (IMRT). Brachytherapy, generally, is not indicated for patients with large prostate size or those with a urethral stricture since the procedure results in short-term swelling of the prostate which can lead to urinaryobstruction. As with all forms of radiation therapy, there are concerns regarding the long-term risk of treatment-related secondary malignancies. There also are reports that suggest that the clinician’s level of experience with brachytherapy is correlated with disease recurrence rates. Studies of permanent brachytherapy have generally utilized either iodine-125 or palladium-103. Use of cesium-131 is also being studied. Use of iodine-125 requires more seeds, and there is thus less dosimetric dependence on any single seed. Permanent brachytherapy may be used alone as monotherapy or may be combined with EBRT (together known as combined modality therapy – CMT) as a way to boost the dose of radiation therapy delivered to the tumor. Again, CMT can be performed with permanent or temporary brachytherapy; however, use with permanent brachytherapy is more common. The brachytherapy boost is typically done 2 to 6 weeks after completion of EBRT, although the sequence can vary.Related Policies:
8.01.33 – High Dose Rate Temporary Prostate Brachytherapy
Policy
Brachytherapy using permanent transperineal implantation of radioactive seeds may be considered medically necessary in treatment of localized prostate cancer when used as monotherapy or in conjunction with external beam radiation therapy (EBRT) (See Policy Guidelines).
Policy Guidelines
Permanent brachytherapy using only implanted seeds is generally used in patients whose prostate cancer is considered low risk. Permanent brachytherapy combined with EBRT is used (sometimes along with androgen deprivation) to treat higher risk disease.
Prostate cancer risk is often defined using the following criteria:
- Low risk: PSA 10 ng/ml or less, Gleason score 6 or less, and clinical stage T1c or T2a.
- Intermediate risk: PSA greater than 10 but 20 ng/ml or less, or Gleason score 7, or clinical stage T2b
- High Risk: PSA > 20 ng/ml or Gleason score 8 – 10, or clinical stage T2c
The procedure is usually performed in 2 stages; a prostate volume study (CPT code 76873) followed on a later date by the implant itself, which is performed in the operating room under general or epidural anesthesia. Iodine or palladium are the typical isotopes used; and the selection of isotope is usually based on physician preference. A CT scan is usually performed at some stage after the procedure to determine the quality of the seed placement.
Benefit Application
BlueCard/National Account Issues
No applicable information.
Rationale
The evaluation of treatment options for clinically localized prostate cancer is difficult because there is minimal evidence comparing various treatments, including active surveillance (“watchful waiting”), in terms of improving clinically meaningful patient outcomes. Even assuming that an intervention can improve outcomes, the variable and often indolent natural history of clinically localized prostate cancer would require randomized trials with follow-up of 10 to 15 years to determine if, for example, brachytherapy, is associated with equivalent or superior long-term outcomes compared to alternative therapies including various types of radiation therapy. These data are not currently available. The lack of these trials makes it difficult to reach strict scientific conclusions regarding the comparative efficacy of brachytherapy with other treatments for localized prostate cancer.
The framework often used in analyzing treatments of localized prostate cancer, given the lack of comparative studies and lack information regarding impact on survival, is to evaluate the effect of the treatment on surrogate endpoints (such as biochemical free survival) and treatment-related complications. Brachytherapy used as Monotherapy The vast majority of the data on brachytherapy consists of uncontrolled case series, which typically report results in terms of PSA (prostate specific antigen) outcomes, as opposed to final health outcomes. Ragde and colleagues report on the 10-year follow-up of patients with prostate cancer treated with brachytherapy, a duration of follow-up rate that is unusual for any treatment of prostate cancer. (1) Among low-risk patients, the freedom from increasing PSA levels was approximately 80%. However, without a comparison group, it is difficult to reach conclusions regarding the relative efficacy of various treatment options. A recent review was conducted on both brachytherapy (permanent) and proton beam therapy. (2) This report concluded that brachytherapy was at least comparable to intensity-modulated radiation therapy (IMRT), a newer type of external beam radiation therapy (EBRT) for localized prostate cancer in terms of clinical effectiveness. This review also concluded that brachytherapy was a high-value technology compared to IMRT. The review also mentions that brachytherapy is a more established therapy than IMRT. Despite identifying 166 studies that met their review criteria for this report, only one study involved an internal comparison of these treatments: a single-center evaluation of toxicity rates in2 different case series of brachytherapy or IMRT. Nearly all of the other studies were relatively small single-center case series of a single modality with evidence further limited by variability in population demographics, disease risk status, and measures of treatment success and treatment-related complications. In this review; at 5 years after diagnosis, survival estimates ranged from 60% to 90% for active surveillance, and 77% to 97% for brachytherapy. This review also estimated acute and late radiation toxicities based on studies identified. This analysis of toxicity was based on studies that used standardized scoring criteria and in general involved a level of severity of 2 or more. For acute gastrointestinal (GI) toxicity, the rate was estimated at 2% for brachytherapy and 18% for IMRT, and for chronic GI toxicity, these rates were 4% and 7%, respectively. For genitourinary (GU) toxicity, acute rates were about 30% for both therapies, and about 15% for chronic toxicity. Erectile dysfunction was 32% in the brachytherapy studies. Seed migration is a unique risk with permanent brachytherapy. This occurs when one or more seeds becomes dislodged and travels to nearby organs such as the bladder or lung. While this has been reported in 6 to 55% of patients, reports of harm are limited to individual case studies. (2) Brachytherapy has become widely accepted among physicians and its speed and convenience compared to external beam radiation are appealing to patients. Therefore, given the baseline uncertainty regarding long-term outcomes associated with any or no treatment of clinically localized prostate cancer, decisions regarding any treatment option for prostate cancer are frequently reframed as an issue of patient preference, even while acknowledging that the decision must be made based on incomplete data.In summary, permanent brachytherapy, as monotherapy, may be considered an option in the treatment of localized prostate cancer. This treatment may be best utilized in men aged greater than 60 with small volume cancer of low-risk disease (Gleason sum < 7, PSA < 10 mg/mL, and stage T1c). (3) Patients in their 50s or younger may not be considered ideal candidates for brachytherapy based on concerns regarding the durability of treatment. Ideally, the cancer should be within a prostate of less than 60 mL volume. Patients with locally advanced prostate cancer may be undertreated by permanent brachytherapy alone.
Brachytherapy Combined with External Beam Radiation Therapy Permanent brachytherapy has also been combined with external beam radiation therapy as a way to boost the total amount of radiation delivered to the prostate cancer; thus increasing the likelihood of increased patient survival. The key studies have recently been reviewed by Hurwitz. (4) This summary included results of 2 phase II cooperative group studies that were designed to assess toxicity and participants were followed up to provide an assessment of treatment efficacy. This subsequent follow-up was to compare results to prior reports from single-institution studies. Patients in these studies had intermediate-risk disease and were treated by EBRT followed by permanent brachytherapy. In the first study (RTOG 0019), 138 patients were treated with 45 Gy of 3D-conformal radiation therapy followed by iodine-125 brachytherapy. These patients had stage T1-2b disease; if the Gleason score was < 7, PSA was between 10 and 20, but if Gleason score was 7, then PSA had to be 20 or less. Thus, these patients are in the intermediate-risk group. The 4-year rate of biochemical recurrence in this intermediate group was 19% using American Society for Radiation Oncology (ASTRO) criteria. Grade 3 and 4 late GU toxicity was 13%, and for late GI toxicity, the rate was 3%. Comments were noted that these rates were higher than are often reported for either treatment alone. However, the total radiation dose was also higher. In this study, use of androgen deprivation was at the discretion of the treating practitioner. Lee et al. reported on complication rates in this study at an earlier time. (5) The 18-month estimate of late grade 3 GU and GI toxicity was 3.3% (Confidence Interval, 0.1% – 6.5%), and no late grade 4 or 5 toxicity had been noted at the time of this earlier report. In the second phase II study (CALBG 99809), 68 patients had EBRT followed by permanent brachytherapy (radioactive iodine or palladium). All patients in this series received androgen deprivation, and side effects from the androgen deprivation were noted frequently. At a median follow-up of 38 months, no treatment failures (biochemical failures) were noted. Long-term grade 2 and 3 toxicities were noted in 16% of the patients.While long-term data from these studies are not yet available, long-term results are available from large cohorts treated at single institutions. For example, Sylvester et al. reported on results of treatment with EBRT followed by permanent brachytherapy. In this series, no androgen deprivation therapy was used. (6) This report was based on a series of 223 consecutive patients treated between 1987 and 1993 at the Seattle Prostate Institute; patients had stage T1 – T3 disease. Permanent brachytherapy was done with radioactive palladium or iodine, 4 weeks after EBRT. In this series, the authors reported 15 year biochemical relapse free survival (BRFS) in the low-risk group of 88%, in the intermediate-risk group of 80%, and in the high-risk group of 53%. In addition, while this was a case series, long-term outcomes were compared to 2 institutions’ results for radical prostatectomy. Results were similar across Gleason score categories, e.g., the relapse-free survival was 25% to 30% for those with Gleason score 7 for the 3 series of patients, but were variable for other prognostic factors such as PSA. The authors note that when they initiated their study they included low-risk patients, but that they now would not use combined modality therapy (CMT) in low-risk patients. In another report from one center, results were summarized for CMT using 3D conformal radiation therapy followed by permanent (palladium) brachytherapy. (7) This involved 282 consecutive patients; 119 were intermediate risk and 124 were high risk. Patients were treated from 1992 to 1996. In this series, 14-year freedom from biochemical progression in the intermediate-risk group was 87% and, in the high-risk group, it was 72%.
No studies were identified that compare various approaches (CMT, 3D conformal RT, and IMRT) for dose escalation (delivering a boost) in prostate cancer. In summary, based on single-institution studies with long-term follow-up, CMT (permanent brachytherapy and EBRT) provides freedom from biochemical recurrence at acceptable risk and is considered an option in patients with intermediate- and high-risk prostate cancer. This treatment approach provides radiation dose to the prostate and extraprostatic coverage as well. National Comprehensive Cancer Network (NCCN) Guidelines The NCCN guidelines for prostate cancer (v.2.2009) note that the cancer-control rates for brachytherapy appear comparable to surgery for low-risk tumors with medium-term follow up. (8) The guidelines also add that for intermediate-risk cancer, brachytherapy may be combined with external-beam RT (40 – 50 Gy) with or without androgen deprivation, but the complication rate increases. The guidelines state thatpatients with very large or very small prostates, symptoms of bladder outlet obstruction, or previous transurethral resection of the prostate (TURP) are not ideal candidates for brachytherapy.
References:
- Ragde H, Elgamal AA, Snow PB et al. Ten-year disease free survival after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray external beam irradiation in the treatment of patients with clinically localized, low to high Gleason grade prostate carcinoma. Cancer 1998; 83(5):989-1001.
- Institute for Clinical and Economic Review (ICER). Brachytherapy/proton beam therapy for clinically localized, low-risk prostate cancer. Available at http://www.icer-review.org/index.php/bt-pbt.html. (Last accessed May 5, 2009).
- Zietman AL. Localized prostate cancer: brachytherapy. Curr Treat Options Oncol 2002; 3(5):429-36.
- Hurwitz MD. Technology Insight: combined external-beam radiation therapy and brachytherapy in the management of prostate cancer. Nat Clin Pract Oncol 2008; 5(11):668-76.
- Lee WR, DeSilvio M, Lawton C et al. A phase II study of external beam radiotherapy combined with permanent source brachytherapy for intermediate risk clinically localized adenocarcinoma of the prostate: preliminary results of RTOG P-0019. Int J Radiat Oncol Biol Phys 2006; 64(3):804-9.
- Sylvester JE, Grimm PD, Blasko JC et al. 15-Year biochemical relapse free survival in clinical stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy: Seattle experience. Int J Radiat Oncol Biol Phys 2007; 67(1):57-74.
- Dattoli M, Wallner K, True L et al. Long-term outcomes after treatment with brachytherapy and supplemental conformal radiation for prostate cancer patients having intermediate and high-risk features. Cancer 2007; 110(3):551-5.
National Cooperative Cancer Network. Prostate cancer. Clinical Practice Guidelines in Oncology, v.2.2009. Available at www.nccn.org/professionals/physician_gls/PDF/prostate.pdf (Last accessed May 1, 2009).
Codes |
Number |
Description |
| CPT | 55875 | Transperineal placement of needles or catheters into prostate for interstitial radioelement application, with or without cystoscopy |
| 76873 | Ultrasound, prostate volume study for brachytherapy treatment planning (separate procedure) | |
| 77326, 77327, 77328 | Brachytherapy isodose calculation, code range | |
| 77402, 77403, 77404, 77406 | Radiation treatment delivery, single treatment area, code range (used for EBRT) | |
| 77776, 77777, 77778 | Interstitial radioelement application, code range | |
| ICD-9 Procedure | 92.27 | Implantation/insertion of radioactive elements |
| ICD-9 Diagnosis | 185 | Malignant neoplasm of the prostate |
| HCPCS | C1717 | Brachytherapy source, high dose rate iridium 192, per source |
| C2638 | Brachytherapy source, stranded, iodine-125, per source | |
| C2639 | Brachytherapy source, non-stranded, iodine-125, per source | |
| C2640 | Brachytherapy source, stranded, palladium-103, per source | |
| C2641 | Brachytherapy source, non-stranded, palladium-103, per source | |
| Q3001 | Radioelements for brachytherapy, any type, each | |
| Type of Service | Oncology | |
| Place of Service | Outpatient | |
Index
Prostate Cancer, Brachytherapy
Radioactive Seeds
Policy History
| Date | Action | Reason |
| 7/31/97 | Add to Therapy section | New policy |
| 12/18/02 | Replace policy | Policy updated and retired; policy statement unchanged, still considered investigational, but additional discussion provided regarding patient preference issues. |
| 05/14/09 | Replace policy | Policy returned to active review. Policy updated and rationale extensively updated. New reference numbers 2 and 4-8 added. Policy statements changed to indicate permanent brachytherapy may be considered medically necessary as monotherapy and when combined with EBRT. |
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