For the first issue of 2006 and of our ninth year, we are excited to have four outstanding and timely review articles, 12 original articles representing the best clinical and translational research and a provocative case report. The journal is doing very well with the impact factor continuing to rise and a very healthy submission rate to both our US and European editorial offices.

Feneley and Constantinou present a very nice overview of the prostate cancer and PSA screening debate. While total PSA as an isolated biomarker may not be as robust as it was in the ‘early PSA era’, data on using PSA velocity or PSA doubling time to provide risk assessment in younger men with low baseline PSA may become more accepted and useful. I certainly agree with them that new molecular biomarkers are vital to better characterize these heterogeneous tumors.

In our second review, Gould and Kirby provide an overview of testosterone replacement for hypogonadism or ‘andropause’. At least in the US as the ‘Baby Boom Generation’ (those born between 1946 and 1964) turns 60 in 2006, their thirst for perpetual youth will keep this a hot topic. It is speculative whether too much or too little testosterone is a risk factor for prostate cancer development and progression. This Editor's opinion is that a eugonadal state is preferable. Certainly, if too much testosterone were causative of prostate cancer, we would expect to see the highest rates in teenagers and young adults!

Medeiros and co-workers explore another hot topic of obesity and prostate cancer risk. They have a nice overview of the lipid biomarker, leptin, and the link of obesity and aggressive prostate cancer. Considering that obesity is an epidemic in the US and other developed Western countries, this portends for an increasing public health threat for prostate cancer.

The final review is an outstanding summary on ‘watchful waiting’ from Gerry Chodak, one of the leading experts in this field. There is no question that the proportion of men with low volume, clinically localized prostate cancer has skyrocketed in the PSA era and many men would seem to be ideal candidates for this approach. However, since we have no completed randomized controlled trials in watchful waiting as a specified treatment, we, as clinicians, have difficulty providing evidence-based treatment recommendations for our patients considering this option. Furthermore, there has been age migration such that younger men are more reluctant to opt for watchful waiting without the knowledge of clear biomarker data on profiling the aggressiveness of their individual case.

Speaking of biomarkers to better risk-assess prostate cancer, there are a number of original articles in this issue that shed more light on putative new markers. While Beebe-Dimmer et al. found that polymorphisms in the PSA gene may not be the answer, Srivastava and co-workers from the US Department of Defense Center for Prostate Disease Research (DoD-CPDR) conducted elegant laser-capture micro-dissection studies of whole-mounted radical prostatectomy specimens suggesting that the PSRG gene may be of future clinical value. Similarly, Anscher and co-workers from Duke University found that the M6P/IGF2R gene may function as a tumor suppressor gene in human prostate cancer also derived from radical prostatectomy specimens. Finally, Liao et al. have implicated QM protein and Diss et al. have suggested neuroendocrine markers, Brn-3a/3c, as clinically relevant biomarkers in the disease. In an interesting basic science study with important clinical implications, Klotz and co-workers from Toronto screened 26 flavonoids for their antiproliferation effects on prostate cancer cell lines finding several promising lead agents. With the tremendous interest in neutraceuticals to prevent and treat prostate cancer, such as flavonoids, this work is intriguing.

There are a number of very interesting clinical original articles in this issue such as Roehrborn et al.'s report on a population-based US National survey for lower urinary tract symptoms (LUTS) and enlarged prostate (EP). Fully, 25% of men reported moderate to severe LUTS and 55% of those consulting a doctor had EP. Again, with the swelling population associated with the Baby Boom Generation, it will be interesting to see how ‘boomers’ deal with LUTS and EP and their health resource utilization for this condition. Speaking of aging, the hot topic of osteoporosis and bone health seems to be in the news more than ever. In this light, Yaturu et al. found that 60% of men on androgen deprivation therapy (ADT) had evidence of osteoporosis. This paper adds to the growing body of literature showing that long-term ADT is associated with bone loss. To combat this, Ferreira et al. report a very interesting series of five men, who had orchiectomy for locally advanced prostate cancer and who were given androgen replacement therapy intermittently to prevent side-effects. Although the experience is small, they report no patient developing metastatic disease from the replacement of androgens.

In other clinical studies in advanced prostate cancer, Harris et al. examined the not often reported issue of the use of nephrostomy to alleviate renal obstruction in men on hormonal therapy. They advocate liberal use of nephrostomy (or stenting) rather than waiting for hormonal therapy to possibly be effective. In Hormone Refractory Prostate Cancer (HRPC), Kalkner et al. treated 17 patients with Octreotide acetate (Sandostatin LAR) finding four clinical responders. The biomarkers Octreotide scintigraphy and Chromogranin-A serum levels were not able to predict responders. In a Greek autopsy study of 212 cases, 40 (18.8%) had incidental prostate cancer. This is lower than the rates seen in the classic contemporary series of Sakr and co-workers from Detroit and may suggest the rate of the disease is lower in this population.

In our case report section, Polascik and co-workers from Duke present a case of focal cryotherapy for radio recurrent prostate cancer in a 75-year-old man. While the fourth generation cryotherapy with very small probes, Argon gas cooling, better computer control, and brachytherapy template delivery seems to have lessened the morbidity of the procedure, the focal aspect of the treatment remains investigational, but certainly appealing.

Thanks again for your support. Until next time, I remain.

Most respectfully,