Is Seeds + External Beam Superior to Seed Implants Alone?
There is no consensus standard defining which patients should be treated with seed implant alone versus combined external beam therapy  plus seed implant. Using the Partin Data it is possible to determine the patients who are likely to have disease outside the capsule of the prostate and who should likely benefit from combining external beam which can treat disease outside the gland. A case can be made to treat all patients with combined therapy since the seed implants are rarely perfect and there can be 'cold spots' in the gland (i.e. areas where the seeds have drifted apart and the dose is lower than the planned dose.)

10 year results after external plus seeds based on Gleason, PSA and PAP (prostatic acid phosphatase) are noted here. The Seattle group has presented data (Blasko, 2000) comparing control rates for seeds alone versus the combination as noted below: More of the Seattle 10 years data for seeds plus external is noted by Gleason and by PSA, and comparisons by therapy for the three risk groups (note that even though it is logical to combine external with seeds there is little evidence that it is superior to seeds alone!)

Control Rates with Radiation
Group Seeds Only Seeds + External Beam
Gleason 6  and PSA < 10 94%/5y 87%/5y
T3 or GS > 6 or PSA > 10 84%/5y 85%/5y
T3, GS> 6, PSA >10 (2 or 3 factors) 54%/5y 62%/5y
 
Contrast the results with seeds alone (Blasko and Beyer papers below) with these other studies that combine external beam irradiation with seeds
 
Cancer J Sci Am 1998 Nov-Dec;4(6):359-63
Simultaneous radiotherapy for prostate cancer: 125I prostate implant followed by external-beam radiation.

Critz FA, Levinson AK, Williams WH, Holladay CT, Griffin VD, Holladay DA

Radiotherapy Clinics of Georgia, Decatur, USA.

From January 1984 through December 1996, 1020 men with clinical stage T1T2N0 prostate cancer were treated by simultaneous radiation: radioactive 125I prostate implantation followed by external-beam radiation. The median pretreatment prostate-specific antigen was 7.5 ng/mL (range, 0.2-188 ng/mL). Implantation was performed by both the retropubic and the transperineal technique, always followed by external-beam radiation. None received hormone treatment. Disease freedom is defined as achieving and maintaining a posttreatment prostate-specific antigen of < or = 0.5 ng/mL. The median follow-up is 3 years (range, 1-14 years). RESULTS: The overall 5- and 10-year disease-free survival rates are 79% and 72%, respectively, after which a plateau is reached. At 5 years posttreatment, significantly better disease-free survival results are documented with simultaneous radiation by the ultrasound technique (92%) compared with the retropubic implant technique (73%).
 
SIMULTANEOUS IRRADIATION FOR PROSTATE CANCER: INTERMEDIATE RESULTS WITH MODERN TECHNIQUES    

FRANK A. CRITZ;

THE JOURNAL OF UROLOGY 2000;164:738-743

From 1992 to 1996, 689 men with clinical stage T1-T2, N0, Nx prostate cancer were treated with ultrasound guided transperineal 125iodine seed implantation followed 3 weeks later by external beam radiation. Disease-free status was defined as the achievement and maintenance of a PSA nadir of 0.2 ng./ml. or less. Median followup was 4 years (range 3 to 7). None of these men received neoadjuvant or adjuvant hormonal therapy. Results: Overall 5-year disease-free survival was 88%. The 5-year rate according to PSA 4.0 ng./ml. or less, 4.1 to 10.0, 10.1 to 20.0 and greater than 20.0 was 94%, 93%, 75% and 69%, respectively. Multivariate analysis revealed that pretreatment PSA was the strongest indicator of subsequent disease-free status in regard to Gleason score or clinical stage.

Int J Radiat Oncol Biol Phys 1998 Sep 1;42(2):289-98

Actuarial disease-free survival after prostate cancer brachytherapy using interactive techniques with biplane ultrasound and fluoroscopic guidance.

Grado GL, Larson TR, Balch CS, Grado MM, Collins JM, Kriegshauser JS, Swanson GP, Navickis RJ, Wilkes MM

Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ, USA.

Brachytherapy using 125I or 103Pd radioactive seeds either alone or in combination with adjunctive external beam radiotherapy (XRT) was administered to 490 patients at a single institution. Actuarial disease-free survival at 5 yr was 79%  and the 5-yr actuarial rate of local control was 98% .Post-treatment PSA nadir and pretreatment PSA level were found to be significant predictors of disease-free survival. In patients with a PSA nadir < 0.5 ng/ml, 5-yr disease-free survival was 93% (95% CI, 84-97%), compared with 25% (95% CI, 5-53%) in patients whose PSA nadir was 0.5-1.0 ng/ml and 15% (95% CI, 3-38) in patients with a PSA nadir > 1.0 ng/ml.
Int J Radiat Oncol Biol Phys 1996 Jul 15;35(5):875-9

103Pd brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma.

Dattoli M, Wallner K, Sorace R, Koval J, Cash J, Acosta R, Brown C, Etheridge J, Binder M, Brunelle R, Kirwan N, Sanchez S, Stein D, Wasserman S

Department of Radiology, University Community Hospital, Tampa, FL 33613, USA.

Seventy-three consecutive patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through 1994. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (71 patients), Gleason score 7-10 (40 patients), prostate specific antigen (PSA) > 15 (32 patients), or elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than 1.0 ng/ml (normal < 4.0 ng/ml).  The overall, actuarial freedom from biochemical failure at 3 years after treatment was 79%.
Int J Radiat Oncol Biol Phys 2000 Mar 1;46(4):839-50

Palladium-103 brachytherapy for prostate carcinoma.

Blasko JC, Grimm PD, Sylvester JE, Badiozamani KR, Hoak D, Cavanagh W

Seattle Prostate Institute, Seattle, WA, USA.

Two hundred thirty patients with clinical stage T1-T2 prostate cancer were treated with Pd-103 brachytherapy and followed with prostate-specific antigen (PSA) determinations. The overall biochemical control rate achieved at 9 years was 83.5%. Failures were local 3.0%; distant 6.1%; PSA progression only 4.3%. Significant risk factors contributing to failure were serum PSA greater than 10 ng/ml and Gleason sum of 7 or greater. Five-year biochemical control for those exhibiting neither risk factor was 94%; one risk factor, 82%; both risk factors, 65%.
: Int J Radiat Oncol Biol Phys 1997 Feb 1;37(3):559-63

Biochemical disease-free survival following 125I prostate implantation.

Beyer DC, Priestley JB Jr

Arizona Oncology Services, Phoenix 85013, USA.

From December 1988 through December 1993, ultrasound-guided brachytherapy was preplanned with 125I and delivered 160 Gy as the sole treatment in 499 patients. With a median follow-up of 35 months (3-70), the actuarial clinical local control is 83%. Both stage and grade are shown to predict for this endpoint. Actuarial biochemical disease-free survival (BDFS) is also correlated with stage, grade, and PSA at presentation. Biochemical disease-free survival at 5 years is 94% for T1, 70% for unilateral T2, and 34% for T2c tumors. Grade is also predictive, ranging from 85% in low-grade tumors to 30% in high-grade tumors. In a multivariate analysis, the pretreatment PSA is most highly correlated (p < 0.0001) with BDFS, local control, and clinical disease-free survival. Patients with a normal pretreatment PSA enjoyed 93% BDFS, while those presenting with PSA > 10 had a BDFS of 40%.