Correspondence *Department of Radiation Oncology, University of California San Francisco, 1600 Divisadero Street, Suite H1031, San Francisco, CA 94143, USA

Email mroach@radonc.ucsf.edu

Introduction

Despite the continued improvements in our ability to deliver high-dose prostate external beam radiation therapy (EBRT), for example the introduction of intensity-modulated radiation therapy (IMRT), beams still enter and exit the patient, putting a number of organs at risk of radiation-induced toxicity. With transrectal ultrasound (TRUS)-guided permanent prostate seed implantation brachytherapy (PPI), however, radiation is delivered directly from within the gland, and allows for intraprostatic doses of radiation that are unachievable by EBRT alone and the convenience of a single-day out-patient procedure.

Patients selected for PPI monotherapy have typically been in the low-risk category: Gleason score <7, serum PSA level 10 ng/ml and clinical stage <T2B.¹ Mature outcomes (median follow-up >60 months) for this risk group at the University of California, San Francisco (UCSF) indicate a 5-year biochemical relapse-free survival rate of >90% (M Roach III, unpublished data), based on the nadir + 2 ng/ml definition for biochemical failure² and a median follow-up of 63 months. Several published reports also indicate durable long-term biochemical control rates of approximately 70–96% (Table 1) in these patients. Furthermore, several outcome analyses for low-risk patients have been performed that indicate that PPI can achieve outcomes equivalent to those of high-dose EBRT and comparable with radical prostatectomy;^{3, 4, 5, 6, 7, 8} however, no randomized controlled trials have been performed to validate these data.

Table 1 Long-term biochemical outcomes (median follow-up >50 months) in patients with low-risk and intermediate-risk prostate cancer who were treated with permanent prostate seed implant brachytherapy alone.

Full tableFigures & Tables indexDownload Power Point slide (309K)

The role of brachytherapy combined with a short course of supplementary EBRT is more controversial, and is an approach used mainly for intermediate- and high-risk patients.¹ Risk groups (low, intermediate, and high) referred to in this Review are classified in accordance with the National Comprehensive Cancer Network Clinical Practice in Oncology Guidelines for Prostate Cancer⁹ unless otherwise specified. The studies highlighted in Tables 1 and 2 were chosen because they used a mature median follow-up, and either reported data according to risk group profiles or in such a way that risk grouping could be determined.

Table 2 Long-term outcomes (median follow-up >48 months) of patients treated with combination permanent prostate seed implant brachytherapy and supplemental external beam radiation therapy.

Full tableFigures & Tables indexDownload Power Point slide (304K)

The evolution of the PPI technique

The PPI technique has evolved over time, from the initial uniform loading of the seeds within the prostate gland, which gives a uniform dose of radioactivity, to the more widely practiced technique of modified peripheral loading. The latter approach is based on the principle of depositing most of the total calculated radioactivity (typically 70–80%) in the periphery of the prostate as opposed to the gland interior (20–30%). The aim is to maximize coverage of the entire prostate gland while minimizing the dose to the urethra and rectum.

At UCSF, using a modified peripheral loading technique, we prescribe 145 Gy for iodine-125 (¹²⁵I) PPI monotherapy (TG-43 dosimetry protocol) and 125 Gy for palladium-103 (¹⁰³P) monotherapy (NIST-99 dosimetry protocol). Our PPI dosimetric criteria for the treatment plan are V100 95–100%, V200 <30%, V150 <65%, and D90 100% (see Box 1 for definitions of dosing). Although various guidelines exist, we have found these parameters to be acceptable, with the caveat to minimize the prostate V200 (below the thresholds mentioned) but not at the expense of target coverage. As we typically do not implant the most posterior row of seeds, rectal dose is not usually an issue. These criteria are to be regarded as general treatment planning guidelines, and adherence is highly dependent on where, and what percentage of, the biopsy sites are positive, and on the TRUS findings.

New technologies have given rise to an increasingly sophisticated implant procedure, including intra-operative treatment planning, targeted brachytherapy to intraprostatic tumor foci, and a choice of isotopes. Furthermore, the use of PPI has evolved from monotherapy for patients with low-risk disease to the combination of EBRT and prostate brachytherapy (with or without androgen deprivation therapy) for patients with higher-risk disease.¹ High dose-rate (HDR) brachytherapy for the prostate will not be discussed as it is outside the scope of this article; however, several reviews have been written on the subject.¹⁰

Treatment planning techniques

Currently, the majority of PPI treatment planning is based on the pre-planned approach. This involves a volume study where contiguous (5 mm intervals) TRUS images of the prostate are taken (while the patient is awake) a few weeks (or days) before the implant is scheduled. As a result, the required seeds and needles can be ordered in advance. Pre-planning also allows for an overall efficient use of operative time, as treatment planning is conducted after and separately from the volume study, as opposed to during the implant (as in the intra-operative technique). Furthermore, treatment plans are not generated with the pressure of the patient being under anesthesia, and the overall duration of anesthesia for the patient is minimized. Since it can take time to learn and perfect the prostate PPI technique,¹¹ pre-planning allows time for the brachytherapy team to evaluate and adjust treatment plans (based on tumor location and anatomy), and then proceed with a given expectation of the implant procedure.

The main disadvantage of this approach lies in reproducing the pre-planned TRUS images (taken with the patient awake) to the intra-operative TRUS images taken at time of implant (with the patient under anesthesia). This step can be challenging and time consuming as the axis, angle, and rotation of the TRUS probe, as well as patient positioning, must be the same. Pre-planning can result in the underestimation or overestimation of the prostate size if the prostate position, volume, and spatial relationship to the rectum and/or urethra have changed relative to that expected. Size discrepancies can result in intraprostatic cold spots, which might increase the risk of biochemical failure, or hot spots, which might increase the risk of toxicity. Other potential difficulties in reproducing and maintaining the pre-planned prostate position include unexpected pubic arch interference, which might result in inaccurate placing of peripheral needles, and changes in the prostate's dimensions as the implant proceeds, caused by edema or traumatic hematoma formation. Once discrepancies are realized, the brachytherapy team must make intra-operative adjustments based on experience as opposed to a new treatment plan.

Reporting of Biochemical control rates following PPI

In the analysis of biochemical control outcome data, one must account for the definition used for biochemical failure. The dominant biochemical failure definition in Tables 1 and 2 is based on the 1997 American Society of Therapeutic Radiation Oncology (ASTRO) Consensus Definition.²⁴ Failure is defined as three consecutive PSA rises above nadir level, with the date of failure defined as a point halfway between the date that nadir was achieved and the first rise in PSA level (backdating), or any increase large enough to result in the initiation of hormonal therapy.²⁴ This definition is, however, sensitive to the length of follow-up, and has a favorable bias for data with short follow-up. It is recommended that the reported date of biochemical control should be listed as 2 years short of the median follow-up reported.² Of note, the data presented in Tables 1 and 2 have not applied the length of follow-up to their reported rates of biochemical control.

A definition of PSA nadir level + 2 ng/ml (with no backdating)²⁵ was recently proposed as the recommended definition of biochemical failure.² This definition might be more robust for retrospective analyses with long-term follow-up, and might help to avoid misinterpretations of biochemical disease status with respect to PSA bounce.^{26, 27} Furthermore, based on a large analysis of 2,693 patients treated with PPI (monotherapy), the nadir + 2 ng/ml definition was found to have the best combination of both sensitivity and specificity (72% and 83%, respectively) for predicting biochemical control.²⁶ Currently, it is recommended that data should be reported based on both definitions.²

Combined therapy: PPI and supplemental EBRT

For patients with Gleason score >6, serum PSA level >10 ng/ml, and disease stage T2B, the question of whether monotherapy PPI is an appropriate treatment arose because of the unfavorable outcomes indicated by early data.^{3, 28, 29} Furthermore, clinicopathologic data was generated that quantified the risk of extracapsular extension (ECE), seminal vesical invasion and lymph node metastases associated with higher-risk clinical features, such as those outlined above.^{30, 31} In addition, pathologic data from radical prostatectomy specimens also revealed that most ECE occurs within 5 mm of the prostate capsule,^{32, 33} as a guide for tumor margin criteria. Since brachytherapy isotopes emit low-energy photons, the sharp dose fall-off results in dose coverage limited to a few millimeters beyond the target volume; therefore, microscopic disease that extends beyond the prostate could be under-dosed unless a sufficient clinical target volume margin is applied beyond the prostate to delineate the treatment volume. Lack of such a margin might explain the early unfavorable results of PPI monotherapy for high-risk patients.

As a result, EBRT alone continues to play a role for higher risk patients in many institutions. As three-dimensional conformal radiation therapy and IMRT technology developed, dose escalation to the prostate plus margin for patients with higher-risk features was investigated. This technology allowed for relative sparing of the rectum and bladder from radiation, along with high prostate doses that were previously thought unachievable. There was a move towards high-dose radiation alone, and the initial PPI monotherapy approach for intermediate- and high-risk patients was not considered standard care.¹

Combined modality therapy refers to the combination of EBRT and PPI. Typically, a dose of 45–50 Gy (1.8–2.0 Gy/day) is delivered to the prostate plus margin (with or without nodal irradiation) followed by a PPI boost (or vice versa). The PPI dose prescribed in these cases is lower than the dose prescribed when used as a primary therapy (because of the EBRT dose and to limit toxicity). Comprehensive guidelines from the American Brachytherapy Society, agreed by a panel of experts, were reported in 1999 to guide patient selection for combined modality therapy.¹ Typically at UCSF, intermediate- and high-risk patients undergo IMRT to the lymph nodes (at risk of metastases), prostate and seminal vesicles (45–50 Gy in 1.8 Gy fractions), followed by a PPI or HDR boost (1–3 weeks post-IMRT). The boost PPI dose used is 110 Gy for ¹²⁵I seeds and 90 Gy for ¹⁰³Pd seeds. We also tend to combine this treatment with a course of neoadjuvant (2 months prior to IMRT) and concurrent androgen deprivation therapy (ADT) for a total of 4 months in intermediate-risk patients, continuing up to a total of 2–3 years for high-risk patients.

Use of Androgen Deprivation Therapy and PPI

Another point to consider in the data presented in Tables 1 and 2 is the use of ADT. ADT is used primarily in low-risk patients to reduce large prostate volumes to meet implant criteria (typically 50–60 ml). Practice varies for intermediate- and high-risk patients, and by extrapolating data from randomized studies that compare EBRT alone versus EBRT plus ADT, there might be a therapeutic benefit in these patients. This treatment combination is highly controversial with respect to brachytherapy, since no randomized trials have been reported that compare brachytherapy (with or without supplemental EBRT) with and without ADT. Several analyses of large cohorts of patients have shown no effect (and potentially an adverse effect⁵³) of short courses (<6 months) of ADT combined with brachytherapy on survival^{53, 54} or biochemical control rates.^{15, 53, 54, 55} As such, the data in Tables 1 and 2 are not separated based on those receiving ADT; the data is uniformly presented based on risk grouping alone.

New imaging techniques and the targeting of intraprostatic tumor FOCI

Endorectal MRI

Endorectal MRI has been shown to provide high-resolution images with 82% accuracy for staging prostate cancer and in the determination of ECE.^{56, 57} This technique enables the peripheral zone to be clearly distinguished from the central zone by its relative T2 hyperintensity. Seventy-five percent of prostate cancers occur within the T2 hyperintense peripheral zone; cancer in this region results in a decrease in the T2 signal (focally or diffusely), allowing for good signal discrimination and diagnostic accuracy. The aim of spectroscopy is to differentiate normal tissue from cancerous tissue according to metabolic differences. Based on the spectral pattern of the prostate tissue, it is the elevated choline + creatine:citrate ratio from the measured peak that gives rise to the suspicion of prostate cancer. Furthermore, a correlation between a significantly elevated choline + creatine:citrate ratio and a Gleason score >6 has been reported.⁵⁸

The superposition of the spectroscopic data onto the prostate endorectal MRI images (MRSI) leads to improved identification of cancer tissue within the gland.⁵⁹ Given that prostate cancer is a multifocal disease, MRSI has the potential to identify intraprostatic tumor targets to allow for selective dose escalation within the gland.^{60, 61, 62, 63, 64} One must acknowledge the limitation of MRI/MRSI, however, in that only gross disease is visualized, and identification of microscopic disease is not yet possible with this technique.

At UCSF, we have also reported the utility of MRSI as an imaging tool for determining treatment success. Of 65 PPI study patients, 100% achieved total metabolic atrophy of their tumors within 48 months.⁶⁵ Metabolic atrophy also precedes PSA decline by a considerable margin, and the long-term clinical effect of total metabolic atrophy is an active area of investigation. Figures 1 and 2 illustrate MRSI images of a patient treated for an intermediate-risk prostate cancer, with a Gleason score of 3 + 3 (positive at the left base, left mid-gland, left apex, right mid-gland and right apex, serum PSA level of 14.2 ng/ml, and tumor stage cT1c). The patient was treated with 2 months of neoadjuvant ADT followed by 2 months of concurrent ADT and EBRT (45 Gy) to the prostate, seminal vesicles and pelvic lymph nodes. An ¹²⁵I PPI boost of 110 Gy was administered upon completion of the EBRT. On his baseline MRSI scan (Figure 1), we observed a clear-cut region of metabolic abnormality within the right base and mid-gland, and a small focus of abnormality in the left mid-gland and apex of the prostate. His follow-up scan 1 year after treatment (Figure 2) demonstrates complete metabolic atrophy throughout the prostate. Currently, 5.5 years after treatment, his serum PSA level remains at the nadir level of <0.1 ng/ml.

Figure 1 Baseline MRSI images of the prostate of a patient with intermediate-risk prostate cancer before treatment with permanent prostate seed implant brachytherapy.

(A) Three consecutive T2-weighted fast-spin echo images showing the dominant region of metabolic abnormality as a region of reduced T2 in the right lobe of the prostate (left side of image). (B) Same T2 weighted images with an overlying 0.3 ml spectral grid. (C) Corresponding ¹H spectra demonstrating a reduction in polyamines and citrate and elevated choline relative to surrounding benign tissue in the same location as the T2 abnormality.

Full figure and legend (43K)Figures & Tables indexDownload Power Point slide (248K)

Figure 2 MRSI images of the prostate of a patient diagnosed with intermediate-risk prostate cancer 1 year after treatment with permanent prostate seed implant brachytherapy.

(A) Three consecutive T2-weighted fast-spin echo images from the same regions as in Figure 1. There is a loss of visualization of the zonal anatomy and pathology on the T2-weighted images; however, the radioactive seeds can be easily visualized. (B) T2-weighted images with an overlying 0.3 ml spectral grid. (C) Corresponding ¹H spectra demonstrating a complete loss of metabolite signals (metabolic atrophy).

Full figure and legend (47K)Figures & Tables indexDownload Power Point slide (251K)

Isotope selection

The two most commonly used isotopes for PPI in North America are ¹²⁵I and ¹⁰³Pd; their physical characteristics are presented in Table 3. Although various analyses have been performed to determine if one is better than the other,¹⁴ the gold standard test is a randomized controlled trial. Such a trial that compares ¹²⁵I with ¹⁰³Pd PPI monotherapy for 600 patients has completed accrual.⁷⁴ Preliminary analysis of morbidity outcomes has been reported for 352 of 600 patients (all patients had a minimum follow-up of 24 months).⁷⁵ As expected, given the short half-life of ¹⁰³Pd (and therefore faster dose rate), American Urology Association urinary symptom scores were greater at 1 month post-PPI and declined to a lower score by 6 months in this treatment group, compared with the group implanted with ¹²⁵I. No significant difference in radiation proctitis rates was reported between the two treatment arms.

Table 3 Isotope physical characteristics.

Full tableFigures & Tables indexDownload Power Point slide (218K)

Preliminary 3-year biochemical control rates have also been reported for 115 of 600 patients, and indicate no significant differences in outcomes between groups receiving the different treatments.⁷⁴ As for arguments that higher-grade tumors might benefit from a more rapid dose rate, this argument remains theoretical since we do not have randomized data; however, a large, retrospective, matched-pair analysis failed to reveal any significant differences in outcome between either isotope and Gleason score at baseline.⁷⁶

Cesium-131 (¹³¹Cs) is a new isotope for PPI that has recently become clinically available. Its physical characteristics are presented in Table 3. This isotope is unique in that its average energy is similar to ¹²⁵I; however, the half life is even shorter than ¹⁰³Pd. Although there are yet to be any published clinical outcomes with this isotope it is currently in clinical use. Given the rapid dose rate, one would expect that the time to PSA nadir would be in the order of that observed with ¹²⁵I. Furthermore, urinary adverse effects would be expected to peak earlier and resolve sooner for ¹³¹Cs PPI than with either ¹²⁵I or ¹⁰³Pd; however, the lower total dose (115 Gy) prescribed might lead to reduced late urethral morbidity. Preliminary work at UCSF (A Sahgal, unpublished data) indicates a lower absolute urethral D30 (dose to 30% of the contoured urethra) with ¹³¹Cs compared with ¹²⁵I. This is to be expected given that the prescribed dose is only 115 Gy, as opposed to 144 Gy with ¹²⁵I. When one accounts for the dose rate by calculating the urethral biologic effective dose (BED) according to the method described by Stock et al.⁷⁷ for prostate BED calculation, normalized to the maximum prostate BED-D90, however, the urethral BED-D30s are found to be comparable (abstract accepted for the October 2007 ASTRO meeting, Los Angeles, USA). Ultimately, long-term clinical data will determine the potential advantage of this new isotope.

Conclusion

The aim of this Review was to highlight current areas of active research and controversy. At USCF, we favor PPI monotherapy for low-risk patients, and PPI or HDR brachytherapy as a treatment boost for intermediate- and high-risk patients following IMRT with the inclusion of ADT. New imaging techniques are emerging with the potential to improve target delineation and help determine the response to treatment, which might improve clinical outcomes.

Acknowledgments

We would like to thank Dr J Kurhanewicz from the University of California, San Francisco for his expertise and help in generating the MRI/MRSI figures. Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

References

1. Nag S et al. (1999) American Brachytherapy Society (ABS) recommendations for transperineal permanent brachytherapy of prostate cancer. Int J Radiat Oncol Biol Phys 44: 789–799 | Article | PubMed | ChemPort |
2. Roach M III et al. (2006) Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 65: 965–974 | Article | PubMed |
3. D'Amico AV et al. (1998) Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280: 969–974 | Article | PubMed | ISI | ChemPort |
4. Sharkey J et al. (2005) ¹⁰³Pd brachytherapy versus radical prostatectomy in patients with clinically localized prostate cancer: a 12-year experience from a single group practice. Brachytherapy 4: 34–44 | Article | PubMed |
5. Kupelian PA et al. (2002) Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: a large single-institution experience with radical prostatectomy and external-beam radiotherapy. J Clin Oncol 20: 3376–3385 | Article | PubMed | ISI |
6. D'Amico AV et al. (2003) Comparing PSA outcome after radical prostatectomy or magnetic resonance imaging-guided partial prostatic irradiation in select patients with clinically localized adenocarcinoma of the prostate. Urology 62: 1063–1067 | Article | PubMed |
7. Brachman DG et al. (2000) Failure-free survival following brachytherapy alone or external beam irradiation alone for T1–2 prostate tumors in 2,222 patients: results from a single practice. Int J Radiat Oncol Biol Phys 48: 111–117 | Article | PubMed | ChemPort |
8. Stokes SH (2000) Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation. Int J Radiat Oncol Biol Phys 47: 129–136 | Article | PubMed | ChemPort |
9. National Comprehensive Cancer Network (2007) NCCN Clinical Practice in Oncology Guidelines for Prostate Cancer v.2.2007 [http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf] (accessed 9 October 2007)
10. Morton GC (2005) The emerging role of high-dose-rate brachytherapy for prostate cancer. Clin Oncol (R Coll Radiol) 17: 219–227 | PubMed | ChemPort |
11. Keyes M et al. (2006) Decline in urinary retention incidence in 805 patients after prostate brachytherapy: the effect of learning curve? Int J Radiat Oncol Biol Phys 64: 825–834 | Article | PubMed |
12. Nag S et al. (2001) Intraoperative planning and evaluation of permanent prostate brachytherapy: report of the American Brachytherapy Society. Int J Radiat Oncol Biol Phys 51: 1422–1430 | Article | PubMed | ISI | ChemPort |
13. Stock RG et al. (2000) Postimplant dosimetry for (125)I prostate implants: definitions and factors affecting outcome. Int J Radiat Oncol Biol Phys 48: 899–906 | Article | PubMed | ISI | ChemPort |
14. Zelefsky MJ et al. (2007) Multi-institutional analysis of long-term outcome for stages T1–T2 prostate cancer treated with permanent seed implantation. Int J Radiat Oncol Biol Phys 67: 327–333 | PubMed |
15. Ash D et al. (2005) The impact of hormone therapy on post-implant dosimetry and outcome following iodine-125 implant monotherapy for localised prostate cancer. Radiother Oncol 75: 303–306 | Article | PubMed | ChemPort |
16. Wilkinson DA et al. (2000) Dosimetric comparison of pre-planned and OR-planned prostate seed brachytherapy. Int J Radiat Oncol Biol Phys 48: 1241–1244 | Article | PubMed | ISI | ChemPort |
17. Shanahan TG et al. (2002) A comparison of permanent prostate brachytherapy techniques: preplan vs hybrid interactive planning with postimplant analysis. Int J Radiat Oncol Biol Phys 53: 490–496 | Article | PubMed |
18. Beyer DC et al. (2000) Real-time optimized intraoperative dosimetry for prostate brachytherapy: a pilot study. Int J Radiat Oncol Biol Phys 48: 1583–1589 | Article | PubMed | ISI | ChemPort |
19. Zelefsky MJ et al. (2003) Improved conformality and decreased toxicity with intraoperative computer-optimized transperineal ultrasound-guided prostate brachytherapy. Int J Radiat Oncol Biol Phys 55: 956–963 | Article | PubMed | ISI |
20. Potters L et al. (2003) Toward a dynamic real-time intraoperative permanent prostate brachytherapy methodology. Brachytherapy 2: 172–180 | Article | PubMed |
21. Raben A et al. (2004) Prostate seed implantation using 3D-computer assisted intraoperative planning vs a standard look-up nomogram: improved target conformality with reduction in urethral and rectal wall dose. Int J Radiat Oncol Biol Phys 60: 1631–1638 | Article | PubMed |
22. French D et al. (2005) Computing intraoperative dosimetry for prostate brachytherapy using TRUS and fluoroscopy. Acad Radiol 12: 1262–1272 | Article | PubMed |
23. Todor DA et al. (2003) Intraoperative dynamic dosimetry for prostate implants. Phys Med Biol 48: 1153–1171 | Article | PubMed | ChemPort |
24. American Society for Therapeutic Radiology and Oncology Consensus Panel (1997) Consensus statement: guidelines for PSA following radiation therapy. Int J Radiat Oncol Biol Phys 37: 1035–1041 | PubMed | ISI |
25. Thames H et al. (2003) Comparison of alternative biochemical failure definitions based on clinical outcome in 4,839 prostate cancer patients treated by external beam radiotherapy between 1986 and 1995. Int J Radiat Oncol Biol Phys 57: 929–943 | Article | PubMed | ISI | ChemPort |
26. Kuban DA et al. (2006) Comparison of biochemical failure definitions for permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 65: 1487–1493 | Article | PubMed | ISI | ChemPort |
27. Pickles T (2006) Prostate-specific antigen (PSA) bounce and other fluctuations: which biochemical relapse definition is least prone to PSA false calls? An analysis of 2,030 men treated for prostate cancer with external beam or brachytherapy with or without adjuvant androgen deprivation therapy. Int J Radiat Oncol Biol Phys 64: 1355–1359 | Article | PubMed |
28. Zelefsky MJ and Whitmore WF Jr (1997) Long-term results of retropubic permanent ¹²⁵iodine implantation of the prostate for clinically localized prostatic cancer. J Urol 158: 23–29 | Article | PubMed | ISI | ChemPort |
29. Kuban DA et al. (1989) I-125 interstitial implantation for prostate cancer. What have we learned 10 years later? Cancer 63: 2415–2420 | Article | PubMed | ChemPort |
30. Partin AW et al. (1997) Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. JAMA 277: 1445–1451 | Article | PubMed | ISI | ChemPort |
31. Kattan MW et al. (1998) A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst 90: 766–771 | Article | PubMed | ChemPort |
32. Davis BJ et al. (1999) The radial distance of extraprostatic extension of prostate carcinoma: implications for prostate brachytherapy. Cancer 85: 2630–2637 | Article | PubMed | ChemPort |
33. Sohayda C et al. (2000) Extent of extracapsular extension in localized prostate cancer. Urology 55: 382–386 | Article | PubMed | ChemPort |
34. Febles C and Valicenti RK (2004) Combining external beam radiotherapy with prostate brachytherapy: issues and rationale. Urology 64: 855–861 | Article | PubMed |
35. Merrick GS et al. (2006) Permanent prostate brachytherapy: is supplemental external-beam radiation therapy necessary? Oncology (Williston Park) 20: 514–522 | PubMed |
36. Roach M III (2003) "Supplemental beam" and prostate brachytherapy: a simple answer to a complicated question? Int J Radiat Oncol Biol Phys 55: 1162–1163 | Article | PubMed |
37. Roach M III et al. (2003) Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol 21: 1904–1911 | Article | PubMed | ISI |
38. Roach M III et al. (2006) Whole-pelvis, "mini-pelvis", or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation Therapy Oncology Group 9413 trial. Int J Radiat Oncol Biol Phys 66: 647–653 | PubMed |
39. Merrick GS et al. (2006) Brachytherapy in men aged 54 years with clinically localized prostate cancer. BJU Int 98: 324–328 | Article | PubMed |
40. Blasko JC et al. (2000) The role of external beam radiotherapy with I-125/Pd-103 brachytherapy for prostate carcinoma. Radiother Oncol 57: 273–278 | Article | PubMed | ChemPort |
41. Sylvester JE et al. (2007) 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 67: 57–64 | PubMed |
42. Merrick GS et al. (2002) Biochemical outcome for hormone-naive intermediate-risk prostate cancer managed with permanent interstitial brachytherapy and supplemental external beam radiation. Brachytherapy 1: 95–101 | Article | PubMed |
43. Merrick GS et al. (2004) Permanent interstitial brachytherapy in younger patients with clinically organ-confined prostate cancer. Urology 64: 754–759 | Article | PubMed |
44. Dattoli M et al. (2007) Long-term prostate cancer control using palladium-103 brachytherapy and external beam radiotherapy in patients with a high likelihood of extracapsular cancer extension. Urology 69: 334–337 | Article | PubMed |
45. Pollack A et al. (2002) Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 53: 1097–1105 | Article | PubMed | ISI |
46. Zietman AL et al. (2005) Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA 294: 1233–1239 | Article | PubMed | ISI | ChemPort |
47. Peeters ST et al. (2006) Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol 24: 1990–1996 | Article | PubMed |
48. Dearnaley DP et al. (2007) Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncol 8: 475–487 | Article | PubMed | ISI |
49. Sathya JR et al. (2005) Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J Clin Oncol 23: 1192–1199 | Article | PubMed |
50. Hoskin PJ et al. (2007) High dose rate brachytherapy in combination with external beam radiotherapy in the radical treatment of prostate cancer: initial results of a randomised phase three trial. Radiother Oncol 84: 114–120 | Article | PubMed |
51. Choi S et al. (2004) Treatment margins predict biochemical outcomes after prostate brachytherapy. Cancer J 10: 175–180 | PubMed |
52. Stone NN et al. (2005) Intermediate term biochemical-free progression and local control following 125iodine brachytherapy for prostate cancer. J Urol 173: 803–807 | Article | PubMed | ISI |
53. Beyer DC et al. (2005) Impact of short course hormonal therapy on overall and cancer specific survival after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 61: 1299–1305 | Article | PubMed | ChemPort |
54. Merrick GS et al. (2006) Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 65: 669–677 | PubMed |
55. Potters L et al. (2000) Examining the role of neoadjuvant androgen deprivation in patients undergoing prostate brachytherapy. J Clin Oncol 18: 1187–1192 | PubMed | ChemPort |
56. Comet-Batlle J et al. (2003) The value of endorectal MRI in the early diagnosis of prostate cancer. Eur Urol 44: 201–207 | Article | PubMed | ChemPort |
57. Hricak H et al. (1994) Carcinoma of the prostate gland: MR imaging with pelvic phased-array coils versus integrated endorectal–pelvic phased-array coils. Radiology 193: 703–709 | PubMed | ChemPort |
58. Kurhanewicz J et al. (2000) The prostate: MR imaging and spectroscopy. Present and future. Radiol Clin North Am 38: 115–138 | Article | PubMed | ChemPort |
59. Coakley FV et al. (2004) Endorectal MR imaging and MR spectroscopic imaging for locally recurrent prostate cancer after external beam radiation therapy: preliminary experience. Radiology 233: 441–448 | Article | PubMed | ISI |
60. DiBiase SJ et al. (2002) Magnetic resonance spectroscopic imaging-guided brachytherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 52: 429–438 | Article | PubMed |
61. Mizowaki T et al. (2002) Towards integrating functional imaging in the treatment of prostate cancer with radiation: the registration of the MR spectroscopy imaging to ultrasound/CT images and its implementation in treatment planning. Int J Radiat Oncol Biol Phys 54: 1558–1564 | Article | PubMed |
62. Pouliot J et al. (2004) Inverse planning for HDR prostate brachytherapy used to boost dominant intraprostatic lesions defined by magnetic resonance spectroscopy imaging. Int J Radiat Oncol Biol Phys 59: 1196–1207 | Article | PubMed | ISI |
63. Zaider M et al. (2000) Treatment planning for prostate implants using magnetic-resonance spectroscopy imaging. Int J Radiat Oncol Biol Phys 47: 1085–1096 | Article | PubMed | ChemPort |
64. Zelefsky MJ et al. (2000) Intraoperative conformal optimization for transperineal prostate implantation using magnetic resonance spectroscopic imaging. Cancer J 6: 249–255 | PubMed | ChemPort |
65. Pickett B et al. (2004) Time to metabolic atrophy after permanent prostate seed implantation based on magnetic resonance spectroscopic imaging. Int J Radiat Oncol Biol Phys 59: 665–673 | Article | PubMed |
66. Ellis RJ et al. (2007) Biochemical disease-free survival rates following definitive low-dose-rate prostate brachytherapy with dose escalation to biologic target volumes identified with SPECT/CT capromab pendetide. Brachytherapy 6: 16–25 | Article | PubMed |
67. Feleppa EJ et al. (2000) Three-dimensional ultrasound analyses of the prostate. Mol Urol 4: 133–139 | PubMed | ChemPort |
68. Feleppa EJ et al. (2004) Recent developments in tissue-type imaging (TTI) for planning and monitoring treatment of prostate cancer. Ultrason Imaging 26: 163–172 | PubMed |
69. Czarnota GJ et al. (1999) Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo. Br J Cancer 81: 520–527 | Article | PubMed | ChemPort |
70. Czarnota GJ et al. (2002) Ultrasound imaging of apoptosis. DNA-damage effects visualized. Methods Mol Biol 203: 257–277 | PubMed | ChemPort |
71. Kolios MC et al. (2002) Ultrasonic spectral parameter characterization of apoptosis. Ultrasound Med Biol 28: 589–597 | Article | PubMed | ChemPort |
72. Czarnota GJ (2005) Role of ultrasound in the detection of apoptosis. Eur J Nucl Med Mol Imaging 32: 622 | Article | PubMed |
73. Chu W et al. (2007) Functional imaging of apoptosis in human tumours with high frequency ultrasound imaging and spectroscopy. Presented at the American Institute of Ultrasound in Medicine Annual Meeting: 2007, March 15–18, New York, NY
74. Wallner K et al. (2002) I-125 versus Pd-103 for low-risk prostate cancer: morbidity outcomes from a prospective randomized multicenter trial. Cancer J 8: 67–73 | PubMed |
75. Herstein A et al. (2005) I-125 versus Pd-103 for low-risk prostate cancer: long-term morbidity outcomes from a prospective randomized multicenter controlled trial. Cancer J 11: 385–389 | Article | PubMed | ChemPort |
76. Cha CM et al. (1999) Isotope selection for patients undergoing prostate brachytherapy. Int J Radiat Oncol Biol Phys 45: 391–395 | Article | PubMed | ChemPort |
77. Stock RG et al. (2006) Biologically effective dose values for prostate brachytherapy: effects on PSA failure and posttreatment biopsy results. Int J Radiat Oncol Biol Phys 64: 527–533 | Article | PubMed |
78. Lawton CA et al. (2007) Results of a phase II trial of transrectal ultrasound-guided permanent radioactive implantation of the prostate for definitive management of localized adenocarcinoma of the prostate (radiation therapy oncology group 98-05). Int J Radiat Oncol Biol Phys 67: 39–47 | PubMed |
79. Martin AG et al. (2007) Permanent prostate implant using high activity seeds and inverse planning with fast simulated annealing algorithm: a 12-year Canadian experience. Int J Radiat Oncol Biol Phys 67: 334–341 | PubMed |
80. Torres-Roca JF et al. (2006) Treatment of intermediate-risk prostate cancer with brachytherapy without supplemental pelvic radiotherapy: a review of the H Lee Moffitt Cancer Center experience. Urol Oncol 24: 384–390 | PubMed |
81. Potters L et al. (2005) 12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urol 173: 1562–1566 | Article | PubMed |
82. Kollmeier MA et al. (2003) Biochemical outcomes after prostate brachytherapy with 5-year minimal follow-up: importance of patient selection and implant quality. Int J Radiat Oncol Biol Phys 57: 645–653 | Article | PubMed | ChemPort |
83. Kwok Y et al. (2002) Risk group stratification in patients undergoing permanent (125)I prostate brachytherapy as monotherapy. Int J Radiat Oncol Biol Phys 53: 588–594 | Article | PubMed |
84. Grimm PD et al. (2001) 10-year biochemical (prostate-specific antigen) control of prostate cancer with (125)I brachytherapy. Int J Radiat Oncol Biol Phys 51: 31–40 | Article | PubMed | ISI | ChemPort |
85. Zelefsky MJ et al. (1998) Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 41: 491–500 | Article | PubMed | ChemPort |
86. Lee WR et al. (2007) Late toxicity and biochemical recurrence after external-beam radiotherapy combined with permanent-source prostate brachytherapy: analysis of Radiation Therapy Oncology Group study 0019. Cancer 109: 1506–1512 | Article | PubMed |
87. Critz FA and Levinson K (2004) 10-year disease-free survival rates after simultaneous irradiation for prostate cancer with a focus on calculation methodology. J Urol 172: 2232–2238 | Article | PubMed |
88. Lederman GS et al. (2001) Retrospective stratification of a consecutive cohort of prostate cancer patients treated with a combined regimen of external-beam radiotherapy and brachytherapy. Int J Radiat Oncol Biol Phys 49: 1297–1303 | Article | PubMed | ChemPort |

Contact the journal about this article

Subject areas under which this article appears: Prostate cancer