What is the role of combined radiation and adjuvant androgen ablation for the treatment of stage T3 prostate cancer?

Updated: Nov 29, 2018
  • Author: Isamettin Andrew Aral, MD, MS; Chief Editor: Edward David Kim, MD, FACS  more...
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Clinical trials have shown significant greater freedom from relapse in patients with advanced local-regional prostate cancer treated with radiation and adjuvant androgen ablation than in those treated with radiation alone. Improved disease control, specifically in patients with stage III disease treated with combined radiation and estrogen, has been noted. Even though treated with both modalities have considerably less favorable disease characteristics, their outcomes are significantly better than those of patients treated with radiation alone.

Adjuvant androgen ablation leads to suppression of the postirradiation rising PSA profile. Patients treated with both radiation and androgen ablation have a significantly decreased incidence of positive findings on postirradiation prostate biopsy samples than patients treated with androgen alone. Therefore, the combination of androgen ablation and radiation probably achieves greater local tumor cell killing than radiation alone does. The incidence of metastatic relapse is low in combined-therapy patients, as is the incidence of distant metastases.

Conventional EBRT as the sole treatment has limited curative potential for patients with clinical stage III prostate cancer. Radiation doses lower than 68 Gy appear to be relatively ineffective. However, patients with pretreatment PSA levels higher than 10 ng/mL have little chance for long-term freedom from PSA relapse, even when treated with the conventional dose limit of 70 Gy. Such patients are best treated with combined radiation and adjuvant androgen ablation or with 3D-CRT dose-escalation protocols.

Patients with PSA levels lower than 10 ng/mL fare relatively better with conventional radiation to a dose-equivalent of 70 Gy in 7 weeks; however, their PSA outcome is also improved by adjuvant androgen ablation.

Publication of results from RTOG 94-13 has given rise to additional debate regarding the use of antiandrogen therapy in conjunction with EBRT. RTOG 94-13 was a phase III, prospective, randomized, clinical trial that compared the sequencing of androgen blockade (ie, before therapy, during therapy, and after therapy) and the size of the radiation field (ie, large field, conventional EBRT vs limited field, and 3D-CRT).

Initial analysis of this trial demonstrated 2 trends. First, in patients presenting with high risk of non–organ-confined disease (ie, Gleason scores of 8-10), larger-field radiotherapy seems to carry a disease-control advantage (ie, treatment of regional pelvic lymph nodes). Second, in patients treated with limited-field radiotherapy (prostate only), sequencing of hormonal therapy (ie, neoadjuvant vs adjuvant) may not be a critical outcome variable.

Note that this trial has not had sufficient time for thorough maturation. Continued follow-up may alter these early results. More specifically, the initial observations may become increasingly significant after longer follow-up periods.

As noted (see above), patients with early-stage prostate cancer, a low Gleason score, and a low PSA level may also benefit from highly localized conformal EBRT. This requires 3-dimensional CT-guided planning with specialized block cutting or multileaf collimation of the external beam in order to deliver the highest possible dose to the prostate gland and to protect the surrounding normal tissues. Results of treatment with this method of delivery are encouraging.

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