Faculty Bibliography

Targeted cryoablation of the prostate has evolved significantly since its reintroduction in the early 1990s. This evolution stems from engineering advancements, procedural refinement, introduction of temperature monitoring, and greater understanding of cryobiology. Recent publications demonstrate durable efficacy for cryoablation, equivalent to other therapies for low-risk disease and possibly superior for moderate- and high-risk prostate cancer. Morbidity following the procedure is mild in comparison with other therapies, with the exception of sexual function impairment. However, longer-term quality-of-life studies show that a significant number of patients return to having intercourse, and late-onset morbidities are not observed. These results contrast with those for radiotherapy--specifically brachytherapy--for which several recent studies document a decline in sexual function, protracted morbidity, and the emergence of late-onset morbidity. Cryoablation is an effective therapy with acceptable morbidity that should be offered as a treatment option to all patients with localized prostate cancer. Furthermore, cryoablation has the potential ability to be tailored to an individual patient's disease. As diagnostic tools and methods continue to advance, it may become possible to target the less aggressive forms of prostate cancer. Focal cryoablation may prove to be an ideal treatment modality in this setting.

OBJECTIVES: To study prospectively the prognostic significance of the reverse transcriptase-polymerase chain reaction (RT-PCR) assay for patients with prostate cancer treated definitively with external beam radiotherapy. The RT-PCR assay for prostate-specific antigen (PSA) has been used to detect circulating prostate cancer cells in the serum of patients with prostate cancer. METHODS: In prospective fashion, serum RT-PCR testing was performed before and/or after definitive therapy, with the results scored as positive or negative. The results were analyzed for 161 patients, and the RT-PCR result was correlated with the treatment outcome. RESULTS: The median follow-up was 29 months. The pretreatment RT-PCR result was not predictive of biochemical relapse-free survival (bRFS) or clinical disease-free survival (DFS). Of 25 patients with T3-T4 tumors, those with a negative pretreatment RT-PCR result had better bRFS and a trend was noted toward better DFS compared with those with a positive result. Among patients with Gleason score 8 to 10 tumor who underwent pretreatment testing (n = 19), those with a negative RT-PCR result had better bRFS and DFS compared with those with a positive result. A trend toward better bRFS was seen for patients with negative versus positive post-treatment RT-PCR results. The DFS was better for patients with negative versus positive post-treatment RT-PCR results. CONCLUSIONS: RT-PCR, when obtained before radiotherapy, may be predictive of outcome for patients with more advanced stages or higher Gleason scores. Post-treatment testing predicted for clinical relapse. Additional study is needed before RT-PCR is used regularly in clinical practice

Radiation therapy is a main form of therapy for patients with localized prostate cancer. Despite advances in delivering radiation beams to the gland, urologists will be faced with managing patients with rising prostate-specific antigen values and radiation-recurrent cancer. If the cancer is detected early, salvage therapy can be initiated. Recent modifications in the technique of salvage cryosurgery have led to the ability to eradicate these tumors with a decrease in morbidity. The management and selection of these patients, as well as the results of salvage cryoablation, are discussed in this article.

PURPOSE/OBJECTIVE:It has been reported that genistein, an isoflavone used in soybeans, has antiprostate cancer effects. Genistein Combined Polysaccharide (GCP trade mark; AMino Up, Sapporo, Japan), a nutritional supplement manufactured in Japan, is composed of genistein and a polysaccharide obtained from basidiomycetes (mycelia) that grows in a variety of mushrooms. METHODS:We report a case of a patient with a biopsy proven prostate cancer showing clinical and pathologic evidence of regression following administration of GCP. The patient was enrolled in an Institutional Review Board (IRB)-approved protocol and received GCP for 6 weeks prior to radical prostatectomy. RESULTS:The patient's prostate-specific antigen (PSA) decreased from an initial value of 19.7 to 4.2 ng/mL after 44 days of low-dose GCP. No cancer was identified in the radical prostatectomy specimen and no side effects were observed in this patient. CONCLUSION/CONCLUSIONS:This case suggests that GCP, which has shown potent inhibitory effects against prostate cancer in vitro, may have some potential activity in the treatment and prevention of prostate cancer.

Benign prostatic hyperplasia (BPH) is a common problem among aging men that produces significant morbidity and health care costs. Contention exists as to whether currently available surgical and pharmacologic options for BPH are appropriate for men in the watchful-waiting stage. Recently, the possible benefits of phytotherapies (plant-derived preparations) in treating BPH and prostate cancer are being considered. Several phytotherapies, including saw palmetto, Pygeum africanum, curbicin, and isoflavone-containing supplements (red clover [Trifoleum pratense] and soy), are widely used in patients with BPH. Evidence suggests that the consumption of isoflavones found in legumes is related to lower rates of BPH and prostate cancer among Asian men. When evaluating natural therapies, the physician should look for a product that relieves symptoms and is safe, contains a health-conferring ingredient with a defined mechanism of action, and is standardized for that ingredient. Phytotherapies, particularly isoflavone-containing supplements, are likely to have an important role in the management of patients in the watchful-waiting stage of BPH.

BACKGROUND:Earlier work from our laboratory highlighted the therapeutic potential of curcumin (turmeric), used as a dietary ingredient and as a natural anti-inflammatory agent in India and other Southeast Asian countries. This agent was shown to decrease the proliferative potential and induce the apoptosis potential of both androgen-dependent and androgen-independent prostate cancer cells in vitro, largely by modulating the apoptosis suppressor proteins and by interfering with the growth factor receptor signaling pathways as exemplified by the EGF-receptor. To extend these observations made in vitro and to study the efficacy of this potential anti-cancer agent in vivo, the growth of LNCaP cells as heterotopically implanted tumors in nude mice was followed. METHODS:The androgen-dependent LNCaP prostate cancer cells were grown, mixed with Matrigel and injected subcutaneously into nude mice. Experimental group received a synthetic diet containing 2% curcumin for up to 6 weeks. At the end point, sections taken from the excised tumors were evaluated for pathology, cell proliferation, apoptosis, and vascularity. RESULTS:Curcumin causes a marked decrease in the extent of cell proliferation as measured by the BrdU incorporation assay and a significant increase in the extent of apoptosis as measured by an in situ cell death assay. Moreover, a significant decrease in the microvessel density as measured by the CD31 antigen staining was also seen. CONCLUSIONS:Curcumin could be a potentially therapeutic anti-cancer agent, as it significantly inhibits prostate cancer growth, as exemplified by LNCaP in vivo, and has the potential to prevent the progression of this cancer to its hormone refractory state.

PURPOSE/OBJECTIVE:Cryosurgical ablation of the prostate has been reported as potential treatment for radioresistant clinically localized prostate cancer. We report our experience with the safety and efficacy of salvage cryosurgery using the argon based CRYOCare system (Endocare, Inc, Irvine, California). MATERIALS AND METHODS/METHODS:Between October 1997 and September 2000, 38 men with a mean age of 71.9 years underwent salvage cryosurgery for recurrent prostate cancer after radiation therapy failed. All patients had biochemical disease recurrence, defined as an increase in prostate specific antigen (PSA) of greater than 0.3 ng./ml. above the post-radiation PSA nadir. Subsequently prostate biopsy was positive for cancer. Pre-cryosurgery bone scan demonstrated no evidence of metastatic disease. In addition, these patients received 3 months of neoadjuvant androgen deprivation therapy before cryotherapy. RESULTS:The PSA nadir was 0.1 or less, 1 or less and greater than 1 ng./ml. in 31 (81.5%), 5 (13.2%) and 2 (5.3%) patients, respectively. Biochemical recurrence-free survival calculated from Kaplan-Meier curves was 86% at 1 year and 74% at 2 years. Reported complications included rectal pain in 39.5% of cases, urinary tract infection in 2.6%, incontinence in 7.9%, hematuria in 7.9% and scrotal edema in 10.5%. The rate of rectourethral fistula, urethral sloughing and urinary retention was 0%. CONCLUSIONS:Our study supports cryosurgery of the prostate as safe and effective treatment in patients in whom radiation therapy fails. Using the CRYOCare machine resulted in a marked decrease in complications.