Prostate cancer continues to be a highly prevalent disease, with estimated 218,890 new cases and 27.050 deaths expected in 2007.[i] At the recent American Urological Association (AUA) annual meeting 2007 in Anaheim CA, presenters have addressed many aspects of the disease from early detection to management of advanced stage. This review attempts to summarize a selection of interesting abstracts presented at the meeting and discuss the possible impact on current management of the disease.  

Inflammation and Carcinogenesis in Prostate Cancer 

The association between infectious agent driven inflammation and carcinogenesis is well established in several cancer types. However, in prostate cancer little is known regarding such association.  Nonetheless, chronic inflammation is a common finding in pathology reports from patients suspected or diagnosed with prostate cancer. One possible explanation is latent or chronic viral infection.  Dong B et al presented a study for characterization of a novel retrovirus DNA sequence from human prostate tissue. The new xenotropic MLV related virus (XMRV) can integrate into host DNA in vivo, that may indicate that XMRV infection may play a role in the initiation of prostate cancer in some men.[ii]  

Detection and Screening of Early Prostate Cancer 

The significance of low PSA-driven prostate biopsy for prostate cancer screening remains controversial.  Analysis of data from the European Randomized Study of screening for prostate cancer (ERSPC) indicated that a 4-year screening interval, based on PSA levels < 3 ng/dl, seems adequate in detecting clinically significant prostate cancer.[iii] However, further long term follow-up is needed to ascertain the pattern of progression in this group and the wide-spread adoption of these recommendations.  

PSA levels can be influenced by several factors. Reports from this year’s AUA meeting linked variations in PSA level to the use of statin medications.  In a study of 1,545 men prescribed statin medications between 1990-2006, the percentage change of PSA was analysed pre and post statin intake, which revealed a significant median drop in PSA of 22.6%.[iv] PSA was also reported to correlate inversely with free testosterone levels in prostate cancer patients.[v] These factors and others reported previously, such as obesity may have a significant collective clinical impact on a cut off of PSA for recommending a prostate biopsy. 

PSA remains the mainstay marker for prostate cancer screening.  However, new genetic based biomarkers are emerging as potentially more accurate tools not only in detecting, but for disease stratification by aggressiveness and predicting recurrence.  At this year’s AUA meeting, a renewed interest in the role of quantitative hypermethylation of specific genes in the detection of localized and risk stratification of prostate cancer has been observed.  Poupret et al reported a frequency of up to 83% of gene methylation of GSTP1 gene in urine samples collected after extended prostate message. The study, which was based on 95 samples from patients diagnosed with localized prostate cancer, also identified a set of 4 genes that express high and cancer specific aberrant methylation in urinary cells that can be used for early detection.[vi] Yang et al from MD Anderson in Texas identified a hypermethylation index using a panel of 3 genes, including GSTP1, with high overall sensitivity (86%) and specificity (82%) in detecting localized prostate cancer. The study was based on 119 patients with PSA< 10 ng/dl who underwent a 10 core prostate biopsy.[vii] Bastian et al studied the frequency of hypermethylation at the CpG Island in serum from 138 patients. They concluded that hypermethylation status of these genes may be a useful marker in men with hormone refractory prostate cancer.[viii]  

Risk Factors Associated with Prostate Cancer

Prostate cancer is associated with a myriad of risk factors, including hormonal milieu changes, environmental and genetic related factors.  Investigators from the University of California, San Francisco and Cleveland Clinic Foundation reported a strong association between over-expression of CPA4 (Carbopeptidase 4, located on chromosome 7q32) and increased risk of aggressive prostate cancer among younger patients (< 66 years old). Similar genetic variations can play a significant role in early identification and aggressive treatment in patients at risk of recurrence after standard local treatment.[ix] 

Based on several preliminary published studies, the level of pretreatment testosterone (T) appears to play a role in prostate cancer initiation and progression. However, the nature of this association is complex. Lane et al reported a prospective study of 380 consecutive patients with clinically localized prostate cancer who underwent radical prostatectomy.  Although the study depicted a trend of association between low pretreatment T (< 220 ng/dl) and predominant Gleason 4 and 5 disease pattern, in a multivariable analysis the trend did not predict biochemical failure (p= 0.07). The authors did not recommend the routine use of T levels as a prognostic tool for predicting progression after definitive local therapy.[x] In another study a significant association was found between the use of antidiabetic medications and the risk of prostate cancer.  However, the decreased risk in this group is probably due to metabolic changes associated with diabetes mellitus, than due to the drug usage.[xi]  

Outcome Analysis and Treatment Options of Localized Prostate Cancer 

The treatment options for localized prostate cancer remain largely dominated by radical prostatectomy with several modifications such as laparoscopic and robotic modifications, and radiation therapy delivered by a myriad of methods. However, the definition of biochemical failure has been illusive for direct comparison purposes between the various modalities of treatment. An interesting critical analysis of the interpretation of biochemical recurrence by applying the new ASTRO definition of failure post radiation (nadir +2) to surgery, indicated a systematic overestimation of cure in radiation patients when compared to standard surgical definition of recurrence free survival.[xii] An interesting retrospective review of 806 RRP of which 336 patients had low risk prostate cancer (PSA<10, Gleason sum ≤ 6 and clinical stage T1,2), showed no survival advantage for performing pelvic node dissection at the time of surgery in the low risk group.[xiii] 

The role of adjuvant androgen deprivation therapy (ADT) in high-risk patients with positive lymph nodes undergoing RRP was clarified further in a large retrospective study of 6,401 patients treated between 1990 and 1999, with median follow up of near 10 years. The authors reported a significant disease specific survival advantage of using adjuvant ADT early in the treatment process.[xiv] Nevertheless, alarming findings from 2 studies presented at the poster sessions, indicating a significant association of cerebrovascular accidents, myocardial infarctions and cardiac mortality with ADT and the duration of intake.[xv],[xvi] 

The advantage of robotic assisted laparoscopic prostatectomy (RALP) over open prostatectomy (RRP) remains a hotly debated topic among urologists and patients alike. In a single institutional review of both modalities on 320 consecutive patients who underwent RALP and 195 undergoing RRP failed to demonstrate a statistically significant difference in the rate of urinary incontinence and time to return to continence within 12 months of follow-up period.[xvii] 

The emphasis on minimally invasive treatment was again evident at this year’s AUA meeting.  The Cryo-on-line data (COLD) registry comprises a large multicenter systematic gathering of data from patients undergoing cryotherapy for prostate cancer. Five year analysis from the registry of 1,198 patients who had undergone primary cryotherapy were followed for up to 5 years, showed a positive biopsy in 82 patients out of 354 patients biopsied. The side effects were minimal, however, only 16.8% of those patients potent at the time of treatment returned to intercourse after the procedure.[xviii]   Furthermore, in another controlled study, which randomized 244 patients between external beam radiation and cryotherapy in localized cancer, reported a comparable survival benefit at 73 months of follow-up between the two modalities of treatment using actuarial survival data and biochemical free survival based on new ASTRO definition.[xix]   

Advanced Prostate Cancer and Salvage Treatment of Prostate Cancer 

Immune therapy represents a new frontier for the treatment of advanced prostate cancer. The interest in immunotherapy in prostate cancer is gaining momentum as our understanding of the mechanism of immunoresponse to cancer cells is clarified further in the near future. In a cohort of 225 men with androgen independent prostate cancer (AIPC) randomized in 2 parallel and identical Phase III trials, the use of dentritic cell product Sipuleucel –T (APC8015, or Provenge®) followed by docetaxel has a significant survival advantage over chemotherapy alone.[xx] 

Preliminary results of the Phase III SPARC study; a large double–blind placebo controlled study of satraplatin for the treatment of metastatic AIPC was presented at this year’s AUA meeting. The authors reported a modest but clinically relevant activity of this drug on time to progression event and pain control. However, this study was not randomized and it only explores the indication for Satraplatin as a second-line therapy in advanced docetaxel-resistant prostate cancer.[xxi] 

Initial results of salvage therapy using minimally invasive technology (MIT) were reported during the meeting in two presentations. The first which reported the use of salvage high intensity focused ultrasound (HIFU) in 167 patients post failed radiation therapy indicated the feasibility of the use of HIFU as a salvage ablation option with curative intent only in patients with localized disease.[xxii] The other study was based on the COLD registry mentioned earlier, whereas, salvage cryotherapy was utilized in 277 patients with biochemical failure post definitive radiation therapy.  The positive biopsy rate was only 6% with average follow-up of 21.6 months. The morbidity profile was favorable in comparison to salvage prostatectomy.[xxiii] Further improvement in technology and safety measures using MIT is expected to increase the popularity of these techniques in the salvage setting of prostate cancer. 

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