Radiation treatment of prostate cancers - the contemporary role of modern brachytherapy techniques.

Life expectancy is rising and the population is ageing in most countries [1]. Prostate cancer (PCa) is the second commonest diagnosed malignancy and it is the fifth leading cause of cancer mortality in men, representing a public health burden worldwide. Furthermore, the majority of PCa (around 62%) is diagnosed in men over 65 years [2].

The use of the prostatic specific antigen (PSA) as a tool for monitoring PCa progression was approved in 1986 by the US Food and Drug Administration, and later, in 1994, its use was accepted also for PCa screening among men aged more than fifty years [3]. With the introduction of PSA testing, there have been a dramatic change in the stage of the disease at the time of diagnosis, with early stages being actually more predominant than advanced stages. Also, a trend in declining mortality due to PCa has been seem, and the major reasons for it may be the progression in the treatment option that include radical prostatectomy in its modalities, hormonal therapy, and a variety of new techniques of radiation therapy, besides the early detection [4].

A recent study comparing the incidence and treatment outcomes of PCa in countries with higher levels of human development and GDP (gross domestic product) per capita, has shown high variations geographically and over time, revealing a greater PCa incidence, but not accompanied by a greater mortality rate due to the disease. A substantial reduction in mortality rates was reported in most countries, except in some Asian countries and Eastern Europe, where mortality increased [5]. Possible explanations for this could be the early diagnosis and easier access to new treatment modalities. Differences in records of incidence and mortality can also be a confounding factor.

Several studies have already provided evidence for the efficacy of dose-escalation on biochemical control (BC) of PCa. Mature results from randomized trials have shown a direct relation between increasing the radiation dose given to the prostate and/or seminal vesicles and BC; however, randomized data comparing different methods of dose escalation are sparse [6, 7, 8, 9].

Traditionally, brachytherapy for the treatment of PCa has been performed using low-dose-rate (LDR) as an effective single modality treatment for low- and intermediate-risk disease, or as a boost to external beam radiation (EBRT) for intermediate and high-risk localized tumors, with excellent results reported by both single and multi-institutional studies [10].

Results of randomized trial ASCENDE-RT that was recently published, compared two methods of dose escalation for the treatment of intermediate- and high-risk PCa. Patients had EBRT – pelvic (46 Gy) followed by a boost with EBRT (78 Gy) or LDR, plus 12 months of androgen deprivation therapy in both arms. As a result, the LDR boost arm doubled the rate of BC, but no significant OS difference was observed between arms [11].

On the other hand, high-dose-rate brachytherapy (HDR) is less frequently used, and most often suggested to boost EBRT. This combination of HDR with EBRT has some advantages and, most of all, the reduction of overall treatment time and increased capability of work load of the linear accelerators, which are of special interest in developing countries, where waiting lists and lack of radiation oncology facilities are a reality. Furthermore, in locally advanced PCa, HDR is able to encompass at least two proximal thirds of the seminal vesicles, whenever necessary, with no risk of seeds discharge after the procedure. High-dose-rate has also a possibility of biological advantage through the delivery of higher doses per fraction, potentializing the biological effective dose given to the prostate, with excellent long terms results regarding BC [12], and low acute and late toxicity [13]. One prospective randomized trial with up to 10 years of follow-up has proved that HDR plus EBRT is more efficient than EBRT alone in terms of BC with less acute rectal toxicity and improved quality of life [14].

The use of HDR as a boost to EBRT and its indication as a sole treatment modality (even with a single dose) has already been reported as favorable by several institutions, but with short-term clinical outcomes [15, 16]. The results of HDR use as monotherapy for early stage low-risk PCa are still missing in the literature, and furthermore, the outcomes from developing countries are practically inexistent, where the technique could be promising as HDR units are relative frequent, due the high incidence of cervix cancer.

Salvage therapy is another indication for prostate brachytherapy, using LDR or HDR, with promising results in terms of efficiency and relative low cost when compared to other techniques [17, 18].

In conclusion, PCa incidence is expected to increase in the near future, straining limited healthcare resources. Despite the fact that comparisons between published series are difficult due differences in the techniques and planning, an appropriate allocation of resources for cancer prevention, early diagnosis, and curative treatments is required worldwide, especially in developing countries.