What further developments in external beam radiotherapy (EBRT) are being investigated for the treatment of prostate cancer?

Updated: Nov 29, 2018
  • Author: Isamettin Andrew Aral, MD, MS; Chief Editor: Edward David Kim, MD, FACS  more...
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Answer

Technical developments have significantly enhanced the ability of external beam radiation therapy (EBRT) to deliver high-dose radiation to the prostate while minimizing the dose delivered to the surrounding structures.

A current trend in well-localized radiotherapy, intensity-modulated radiotherapy (IMRT), has enhanced the precision of conformal therapy. IMRT further minimizes the toxicities associated with conventional EBRT. In addition, careful target assessment both before and during each fraction of therapy (ie, image-guided radiotherapy [IGRT]) has become a current standard of care. Whether image guidance will allow more successful dose escalation is uncertain.

Doses previously considered unsafe for clinical use have become current standards. Patients with early-stage prostate carcinoma typically receive doses in the range of 72-78 Gy. Those with more advanced disease are commonly offered doses that approach 80-82 Gy.

Prospective data suggest that in certain groups of patients, increasing the dose yields improved disease control; however, dose escalation can be safely accomplished only with the use of modern technology (eg, IMRT and IGRT) and the assistance of technically proficient staff (including physicists, dosimetrists, and therapists). The role of chemotherapy in patients with locally advanced disease continues to evolve.

Current clinical trials are attempting to address the potential advantages of adding taxane-based therapy to EBRT and androgen blockade. Chemotherapy in conjunction with radiotherapy should not be considered a current standard; rather, it is a potential alternative that is still undergoing clinical investigation.

Patients with early-stage disease (ie, T1c/T2a) who are at a low risk of extracapsular disease extension (ie, prostate-specific antigen [PSA] level of 10 ng/mL or lower and Gleason score of 6 or lower) may opt for either EBRT or permanent prostate implants (brachytherapy) if they do not wish to undergo surgery.

Current literature suggests that conformal radiotherapy reduces the morbidity associated with EBRT; this may also be particularly true of IMRT. An additional benefit of this form of therapy is the ability to offer an increased dose to the primary target. In turn, this should improve bNED (biochemical, no evidence of disease) control rates.

Patients with early-stage disease who have either an increased PSA level (≥ 10 ng/mL) or an elevated Gleason score (≥ 7) likely require aggressive therapy. Dose-escalation studies suggest that many of these patients may benefit from higher doses of local therapy. Data that assess the role of androgen blockade in this setting should be available within the next few years.

Patients with more advanced disease (T2b and higher) appear to benefit from combined treatment including total androgen blockade (TAB) and radiotherapy. Several prospective studies have shown improved bNED control rates when both forms of therapy are offered. Protracted use of TAB after radiotherapy may also confer a survival advantage. This issue also awaits further clarification from the follow-up of completed clinical trials.

Patients who are at high risk and have poor prognostic features may be treated more effectively by adding systemic therapies and androgen ablation.

The advent of new techniques such as patient immobilization devices, computed tomography (CT) planning, beam’s-eye view (BEV) visualization and planning, 3-dimensional dose calculation, multileaf collimation, and electronic portal imaging has significantly improved the management of prostate cancer, resulting in increased radiation doses to the prostate. At the same time, these technologies have enabled a reduction in the normal tissue volume that receives clinically significant doses of radiation, thus minimizing complication rates.

Radiation oncology will continue to offer great benefit to patients with carcinoma of the prostate. IGRT appears especially promising in the management of this disease. Ongoing clinical trials should help solidify the role of this approach in the treatment of patients with prostate cancer.

Combined use of antiandrogen therapy and radiotherapy has been shown to markedly affect bNED control rates in patients with locally advanced disease. In Radiation Therapy Oncology Group (RTOG) trial 94-08, patients with intermediate-risk prostate cancer obtained a significant survival benefit from antiandrogen therapy; survival was not improved in patients with low-risk disease. [30]

Lee et al analyzed prostate cancer-specific mortality (PCSM) according to treatment-specific nomogram-predicted risk of biochemical recurrence (BCR) for men treated by radical prostatectomy (RP), external-beam radiation therapy (EBRT), and brachytherapy. [31] The authors studied more than 13,800 men who underwent RP, EBRT, or brachytherapy in an 18 year period at two academic medical centers. The 5-yr progression-free probability (5Y-PFP) was calculated for each patient based on the treatment received using a validated treatment-specific nomogram to predict biochemical recurrence. Men receiving EBRT had higher 10-yr PCSM compared with those treated by RP across the range of nomogram-predicted risks of BCR. After adjusting for nomogram-predicted 5Y-PFP, EBRT was associated with a significantly increased PCSM risk compared with RP. EBRT patients with similar nomogram-predicted 5Y-PFP appear to have a significantly increased risk of PCSM compared with those treated by RP. [31]


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