Abstract and Introduction
While the majority of men with localized prostate cancer who undergo a radical prostatectomy will remain disease free, men with certain clinical and pathological features are known to be at an increased risk for developing a biochemical recurrence and, ultimately, distant metastatic disease. The optimal management of these patients continues to be a source of controversy. To date, three randomized Phase III trials have demonstrated that adjuvant radiation therapy (ART) for patients with certain adverse pathological features results in an improvement in several clinically-relevant end points, including biochemical recurrence-free survival and overall survival. Despite the evidence from these trials showing a benefit for ART, many believe that ART results in overtreatment and unwarranted treatment morbidity for a significant number of patients. Many physicians, therefore, instead advocate for close observation followed by early salvage radiation therapy (SRT) at the time of a biochemical recurrence. The purpose of this review is to evaluate the evidence for and to distinguish between ART and early SRT. We will also highlight current and future areas of research for this patient population, including radiation treatment dose escalation, hypofractionation and androgen deprivation therapy. We will also discuss the cost–effectiveness of ART and early SRT.
Prostate cancer (PC) is the most common noncutaneous malignancy and the second leading cause of cancer-related death among men in the USA. The American Cancer Society estimated that over 240,000 men will be diagnosed with PC within the USA in 2011. Nearly 50% of patients with localized PC will opt for primary treatment with radical prostatectomy (RP).
While the majority of patients undergoing RP remain free of disease, patients with certain adverse pathological features (APFs) are at an increased risk for developing a PC recurrence in the future. APFs that have been significantly associated with an increased chance for a biochemical recurrence include extracapsular extension (ECE), seminal vesicle invasion (SVI), disease present at a surgical margin(s) (SM), higher preoperative prostate-specific antigen (PSA) and a Gleason score (GS) ≥7. The 5-year biochemical progression rate for patients with APFs has been estimated to be as high as 40–60%.
Patients with such APFs typically fall into one of three categories:
Those who will never have a local or distant recurrence in spite of having APFs;
Those who will develop a local recurrence and who will benefit from adjuvant local therapy;
Those with distant micrometastatic disease at the time of surgery, who will not benefit from adjuvant local treatment.
Differentiating between these categories to identify patients who will benefit from adjuvant local therapies has been a continued source of controversy.
Two treatment approaches for the postoperative management for this patient population are adjuvant radiation therapy (ART) or observation followed by early salvage radiation therapy (SRT). ART is typically defined as radiation therapy (RT) initiated shortly after RP, based upon information from pathological review of the RP specimen in men with an undetectable PSA (typically <0.2 ng/ml). SRT, on the other hand, is defined as RT that is withheld until the time a patient develops a biochemical recurrence.
While there is currently no level I evidence to address the issue of ART versus SRT, multiple randomized controlled trials have examined the role of immediate ART versus observation for men with high-risk APFs (ECE, SVI and positive SMs). Three separate Phase III trials have uniformly shown a biochemical progression-free survival (bPFS) advantage in favor of immediate ART (Table 1).[4–7] One trial, with a longer follow-up, also demonstrated an overall survival advantage for patients treated with ART. However, since the publication of these trials, patterns of care for use of ART for eligible patients have remained unchanged within the USA. It is estimated that <20% of patients who qualify for ART based on APFs receive it, at this time.[9,10]
The purpose of this article is to review the rationale and risks associated with the different treatment approaches for postoperative management of patients at high risk for a biochemical recurrence following a RP. We will also highlight current and future areas of research for this patient population.
Future Oncol. 2011;7(12):1429-1440. © 2011 Future Medicine Ltd.