ADT + radiotherapy in the treatment of high-risk prostate cancer ...

A new review published recently in the British Journal of Cancer addresses appropriate current practice regarding the use of neoadjuvant and adjuvant androgen deprivation therapy (ADT) in combination with radiation therapy in the management of patients with high-risk localized and locally advanced forms of prostate cancer.

Payne and Mason begin by noting the historic role of ADT in the treatment of advanced and metastatic forms of prostate cancer. However, over the past 20 years there has been increasing evidence to support the combination of ADT with various forms of radiation therapy for the treatment of localized and locally advanced prostate cancer. These uses of ADT in combination with radiation therapy include:

• The use of ADT for as little as a month prior to brachytherapy (neoadjuvant ADT) to simply shrink large prostates down to about 45 cm³ or smaller, and thus increase the effectiveness and safety of brachytherapy
• The use of ADT before external beam radiation therapy (neoadjuvant ADT) to improve rates of biochemical recurrence-free survival in men receiving external beam radiation therapy as first-line treatment for (usually intermediate- and high-risk forms of) localized prostate cancer
• The use of ADT before, during, and after external beam radiation therapy (neoadjuvant and adjuvant ADT) to improve rates of biochemical recurrence-free and overall survival in men receiving external beam radiation therapy for locally advanced forms of prostate cancer
• The use of ADT before, during, and after external beam radiation therapy (neoadjuvant and adjuvant ADT) to improve rates of biochemical recurrence-free and overall survival in men receiving external beam radiation as salvage therapy after prior failure of other forms of first-line therapy (e.g., radical prostatectomy)

Indeed, there are multiple ways in which ADT can now be combined with radiation therapy to treat a wide range of men with prostate cancer at various stages in its progression ? and there are many forms of ADT that can now be used in such treatment strategies.

The full text of this review article is not easily accessible on line, but Payne has provided a little more information from the paper in a ?Beyond the Abstract? commentary on the UroToday web site.

Like many radiation oncologists, Payne now considers that, ?The use of neoadjuvant or adjuvant ? ADT ? in combination with radiotherapy ? is now ? the standard of care in patients with high-risk localized or locally advanced prostate cancer.? Others might debate that under selected circumstances, but it is certainly the case that combinations of radiotherapy and ADT are highly appropriate treatment options for a wide variety of men with higher-risk and locally advancing forms of prostate cancer today. The hard thing is selecting the very best combination if a combination is appropriate and minimizing any risk from the side effects of ADT wherever possible.

As yet unanswered questions identified by Payne in addressing the most appropriate uses for combinations of ADT with radiation therapy include the following:

• How do we select the most appropriate patients for neoadjuvant or adjuvant ADT, given that there is no universally accepted definition of high risk or, indeed, locally advanced disease?
• When should adjuvant therapy be started and for how long should it be continued?
• Should neoadjuvant and adjuvant therapy be used in combination?
• How should we be thinking about combining newer hormonal agents (abiraterone acetate, orteronel, and MDV3100) with radiation therapy in appropriately selected patients?

The original article by Payne and Mason includes a full discussion on the many combination trials from which we now have long-term data, such as RTOG 86-10, TROG 96.01, RTOG 85-31, EORTC 22863, RTOG 92-02, SPGC-7/SFUO-3, and PR3/PR07. For this reason alone, this may be a good reason for support group leaders to track down a full-text copy of this review.

There are good clinical reasons for continuing to look hard at the potential for combinations of radiation therapy and ADT in the management of localized and locally advanced forms of prostate cancer:

• We know that ADT can reduce prostate size, allowing greater focus of radiation therapy.
• We know that modern forms of radiation therapy can be delivered with very high accuracy (compared to even the late 1990s).
• We know that ADT can significantly impact the micrometastases associated with high-risk and locally advanced disease.
• We know that the LHRH antagonist degarelix can lower PSA and testosterone levels faster than the LHRH agonists.
• We know that under certain circumstances the combination of ADT with radiation therapy can significantly extend disease-specific and overall survival.

The critical question is going to be whether greater sophistication in the use of various combinations of radiation therapy and ADT can show greater benefits in delaying biochemical progression, delaying the onset of metastasis, and delaying the need for chemotherapy. Such progress certainly ought to lead to further extensions in disease-specific and overall survival.

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Filed under: Living with Prostate Cancer, Management, Treatment Tagged: | "high risk", ADT, androgen deprivation, localized, locally advanced, outcomes, radiation therapy, survival

Source: http://prostatecancerinfolink.net/2012/03/22/adt-radiotherapy-in-the-treatment-of-high-risk-prostate-cancer-todays-best-practices/

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