Prostatic Neoplasms: Moul JW

Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen CM, Anonymous00324. · American Urological Association Education and Research, Inc. · J Urol. · Pubmed #17509297 No free full text.

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Scher HI, Eisenberger M, D'Amico AV, Halabi S, Small EJ, Morris M, Kattan MW, Roach M, Kantoff P, Pienta KJ, Carducci MA, Agus D, Slovin SF, Heller G, Kelly WK, Lange PH, Petrylak D, Berg W, Higano C, Wilding G, Moul JW, Partin AN, Logothetis C, Soule HR. · Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. · J Clin Oncol. · Pubmed #14752077 No free full text.

Abstract: PURPOSE: To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA). RESULTS: Hypothesis: A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population. Patient Population: The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed. Intervention: Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation. Outcomes: An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned. Trial Design: The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative. CONCLUSION: Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.

Moul JW. · No affiliation provided · J Urol. · Pubmed #18930259 No free full text.

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Moul JW. · No affiliation provided · Prostate Cancer Prostatic Dis. · Pubmed #18711369 No free full text.

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Moul JW. · No affiliation provided · Prostate Cancer Prostatic Dis. · Pubmed #18268507 No free full text.

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Kirby R, Moul JW. · No affiliation provided · Prostate Cancer Prostatic Dis. · Pubmed #15592438 No free full text.

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Moul JW. · No affiliation provided · Cancer. · Pubmed #12124817 links to  free full text

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Moul JW. · No affiliation provided · J Urol. · Pubmed #11792911 No free full text.

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Moul JW, Mouraviev V, Sun L, Schroeck FR, Polascik TJ. · Division of Urologic Surgery and Duke Prostate Center (DPC), Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. · Curr Opin Urol. · Pubmed #19195129 No free full text.

Abstract: PURPOSE OF REVIEW: This review highlights current features of the changing landscape of the US population with newly diagnosed prostate cancer and discusses new treatment options utilizing noninvasive or minimally invasive management. RECENT FINDINGS: Recent evidence of significant changes in the current prostate cancer landscape is based on clinical data and pathological specimens after radical prostatectomy that suggest a further increase of the low-risk patient population that may require reconsideration of treatment options. For a select cohort of patients with low-risk features, based on the D'Amico definition, active surveillance or focal ablative therapy may be a rational alternative to surgical prostatectomy or whole-gland radiation therapy that still dominate as the main treatment approaches for localized prostate cancer. SUMMARY: As the prostate-specific antigen era continues to mature, we continue to witness stage migration. A growing segment of the localized prostate cancer patient population has very low-volume, low-grade disease. Although active surveillance may be an appropriate approach for a selected group of patients, the progression requiring whole-gland therapy remains a challenge. Organ-sparing focal therapy might ideally fill the gap between a surveillance strategy and whole-gland treatment providing a reasonable balance between cancer control and quality of life.

Moul JW, Bañez LL, Freedland SJ. · Division of Urologic Surgery, Duke Prostate Center, Duke University Medical Center,Durham, NC 27710, USA. · Oncology (Williston Park). · Pubmed #18077992 No free full text.

Abstract: Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in two main clinical settings: (1) rising PSA to signal failed initial local therapy and (2) rising PSA in the setting of early hormone-refractory prostate cancer prior to documented clinical metastases. Most urologists and radiation oncologists are very familiar with the initial very common clinical scenario, commonly called "biochemical recurrence." In fact, up to 70,000 men each year will have a PSA-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based upon the patient's risk of progression and the likelihood of success and the risks involved with the therapy. It is unknown how many men per year progress with rising PSA while on hormonal therapy without documented metastases. This rising PSA disease state is sometimes called, "PSA-only hormone-refractory prostate cancer." As in the setting of initial biochemical recurrence, evidence-based treatment options are limited, and taking a risk-stratified approach is justified. In this article, we will explore these prostate cancer disease states with an emphasis on practical, clinically applicable approaches.

Nosnik IP, Gan TJ, Moul JW. · Duke University School of Medicine, Division of Urology, Box 3707, Durham, NC 27710, USA. · Expert Rev Anticancer Ther. · Pubmed #17892432 No free full text.

Abstract: The introduction of robotic laparoscopic assisted prostatectomy at our institution and nationwide has been a great advancement and has caused us to focus and fine-tune our goal for improvements in prostate cancer outcomes whether the patient elects for robotic laparoscopic assisted prostatectomy or open minimally invasive radical retropubic prostatectomy. While these authors favor the open technique performed by highly skilled urologic surgical oncologists, the lessons we have learned to date suggest that it is the skill of the surgeon that determines outcome, regardless of whether or not the operation is performed by an open or robotic laparoscopic technique. The concepts we have articulated here are related to resection and avoidance of positive margins, limited intraoperative blood loss and pain control, which allow equivalence in these outcome areas, regardless of technique.

Burnett AL, Aus G, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus S, Liebert M, Moul JW, Tangen C, Thrasher JB, Thompson I, Anonymous00008. · The Johns Hopkins Hospital, 600 North Wolfe St., Marburg 407, Baltimore, Maryland 21287-2411, USA. · J Urol. · Pubmed #17570435 No free full text.

Abstract: PURPOSE: In conjunction with the assignment to update the Guidelines for Management of Clinically Localized Prostate Cancer, the American Urological Association Prostate Cancer Guideline Update Panel performed a side analysis of the reporting of erectile function outcomes in this clinical context as published in the medical literature. MATERIALS AND METHODS: Four National Library of Medicine PubMed(R) Services literature searches targeting articles published from 1991 through early 2004 were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions. RESULTS: Based on inclusion criteria 436 articles were selected. Of these articles database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function and intact erectile function that were 26% to 100%, 16% to 48% and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47% and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes. CONCLUSIONS: Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.

Freedland SJ, Moul JW. · Division of Surgery, Durham Veterans Affairs Medical Center, Durham, NC, USA. · J Urol. · Pubmed #17509277 No free full text.

Abstract: PURPOSE: We estimate that approximately 70,000 men yearly have prostate specific antigen-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear. Treatment must be individualized based on the patient risk of progression, the likelihood of success and the risks involved with the therapy. However, to do so the risks and benefits of the various options must be known. Therefore, we provide a comprehensive overview of the natural history and treatment options for men with prostate specific antigen-only recurrence. MATERIALS AND METHODS: A literature review and overview of prostate specific antigen-only recurrence after failed definitive therapy was done. RESULTS: The natural history after prostate specific antigen-only recurrence is long but variable. Median time from prostate specific antigen-only recurrence after radical prostatectomy to prostate cancer death exceeds 16 years, although some men die within 1 year after PSA recurrence. Rapid prostate specific antigen doubling time is the best prognostic factor for poor outcome. Salvage radiation therapy after radical prostatectomy results in a 45% 4-year prostate specific antigen response rate, although long-term outcomes appear poor. To our knowledge the effect on survival is not known. Salvage radical prostatectomy is rarely performed but in the highly selected patient it may provide some benefit. There are no randomized studies of early vs late hormonal therapy for men with prostate specific antigen-only recurrence. A retrospective study suggested delayed metastasis when therapy was begun early but only in men at high risk. This mirrors other data suggesting that men at high risk may derive significant benefits from early hormonal therapy, whereas men at low risk are unlikely to benefit and may be harmed by hormonal therapy. CONCLUSIONS: Prostate specific antigen-only recurrence is the most common form of advanced prostate cancer. Optimal salvage treatments and timing of these treatments remain controversial.

Robinson MR, Moul JW. · Division of Urologic Surgery, Duke University Medical Center, Duke University School of Medicine, Durham, NC 27710, USA. · Curr Urol Rep. · Pubmed #17459269 No free full text.

Abstract: Radical retropubic prostatectomy and radiation therapy remain the mainstay of treatment for localized prostate cancer. However, with the advent of the Internet, more patients are arriving in physicians' offices questioning novel techniques for their treatment that they otherwise would not have discovered. This paper discusses several of these techniques, including focal cryotherapy, high-intensity focused ultrasound, robotic-assisted laparoscopic prostatectomy, diets, supplements, and hormonal therapy. We also render our opinion on their efficacy for treatment based on the available published studies.

Fitzsimons NJ, Sun L, Moul JW. · Division of Urologic Surgery and Duke Prostate Center, Duke University Medical Center, Durham, NC 27710, USA. · Expert Rev Med Devices. · Pubmed #17359227 No free full text.

Abstract: Prostate cancer is an extremely prevalent problem, especially in our aging population. The prostate-specific antigen test has revolutionized prostate cancer screening. Significant advances have been made in the usage of prostate-specific antigen and its derivatives, biomarkers, diagnostic imaging techniques, biopsy strategy, biopsy needle design and anesthetic agents. Further improvement in prostate cancer detection hinges on the development of an imaging technique that is tumor specific and sensitive to biological aggressiveness.

Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen C, Thrasher JB, Thompson I. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · J Urol. · Pubmed #17222629 No free full text.

Abstract: PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

Moul JW, Ward JF. · Division of Urologic Surgery, Duke Prostate Center, Duke University Medical Center, Duke South, Durham, NC 27710, USA. · Hematol Oncol Clin North Am. · Pubmed #16861121 No free full text.

Abstract: PSA-only recurrence after definitive RP or RT for PCA is an increasingly com-mon scenario. The very definition of advanced prostate cancer is changing. Multimodal therapy improves cancer-specific outcomes especially in men with high-risk disease. After RP, a detectable serum PSA has been considered suggestive of PCA recurrence. After RT, the ASTRO definition of BCR has been widely used to define BCR. Both of these definitions of BCR are subject to dispute. The kinetics of a rising PSA (PSA doubling time) appears to be the best surrogate marker for disease risk, clinical progression, and ultimately cancer-specific death.Therapeutic options include salvage RT after primary RP or systemic HT through surgical/chemical castration, antiandrogens, or nontraditional HT. Re-cent studies suggest that early HT can provide modest survival benefits, but at both an economic cost and decreased quality of life. The diminished side effects of an oral antiandrogen are appealing, and may be as efficacious as castration therapies in low-volume disease.More clinical trials are needed to determine the best treatments, alone and in combination. The potential opportunities for novel therapeutic agents with low associated morbidity are great.

Freedland SJ, Krupski TL, Moul JW. · Department of Surgery, Division of Urology, Duke University School of Medicine, Durham, NC 27710, USA. · Curr Opin Urol. · Pubmed #16679854 No free full text.

Abstract: PURPOSE OF REVIEW: The purpose of this review is to summarize single-institution prostate-cancer-outcomes databases (which are most commonly derived from large academic medical centers, Veterans Affairs medical centers, and military hospitals) to summarize the design and development of three well characterized outcomes databases that combine data from multiple sites (Carcinoma of the Prostate Strategic Urological Research Endeavor, Center for Prostate Disease Research, and the Shared Equal Access Regional Cancer Hospital database) and to use the examples of obesity and prostate-specific antigen changes over time to highlight the importance of these databases in prostate-cancer outcomes. RECENT FINDINGS: Multiple databases have demonstrated that obese men are at greater risk of biochemical progression following radical prostatectomy. In addition, objective data have shown that it is more difficult to operate on obese men leading to greater risk of positive surgical margins, which may contribute to poorer outcomes. Several databases have shown that a rapidly increasing prostate-specific antigen, measured either before diagnosis or after failed primary therapy, is associated with increased risk of prostate-cancer-specific mortality. SUMMARY: Outcomes databases are extremely useful tools. They have lead to dramatic improvements of our understanding of prostate cancer. The challenge is to use this information from past patients to help us better manage our current and future patients.

Moul JW. · Division of Urologic Surgery and Duke Prostate Center, Duke University Medical Center, DUMC 3707, Durham, NC 27710, USA. · Curr Pharm Des. · Pubmed #16515495 No free full text.

Abstract: Prostate cancer recurrence (after prior local treatment) that is detectable only by a rise in serum prostate specific antigen (PSA) level is a very common problem facing clinicians. Given that the majority of contemporary era men with PSA-only or biochemical recurrence are relatively young and otherwise healthy, treatment requires approaches that both improve clinical outcomes and preserve quality of life. Treatment is in one of two broad categories, additional local therapies, termed "salvage" local therapy and systemic therapies. For radical prostatectomy patients, salvage external beam radiotherapy to the prostate bed is commonly employed, being reserved for early biochemical recurrence in men with low risk at distant metastases. For primary radiation patients, salvage radical prostatectomy or cryotherapy can similarly be used for those men felt not to harbor distant metastases. Systemic therapy generally involves hormonal therapy. Traditional hormonal therapy (orchiectomy, luteinizing hormone-releasing hormone agonists or maximum androgen blockade) is the current mainstay of systemic treatment for biochemical recurrence, although non-traditional approaches, such as antiandrogen monotherapy, are increasingly being used. There is a critical need for new pharmaceutical agents to treat this growing stage of prostate cancer. However, it has been difficult to demonstrate efficacy due to the long natural history until death and the survival endpoint currently required by the U.S. Food and Drug Administration. New data show that PSA Doubling time (PSA-DT) during PSA recurrence may be a valid surrogate for death from the disease and may be used to accelerate drug approval. This monograph will attempt to provide a complete balanced discussion of the evaluation and treatment of biochemical recurrence of prostate cancer after prior primary local therapy.

Ward JF, Moul JW. · Nevada Cancer Institute, Las Vegas, Nevada, USA. · Nat Clin Pract Urol. · Pubmed #16474760 No free full text.

Abstract: An estimated 20-40% of men experience a biochemical recurrence within 10 years of definitive prostate cancer treatment. No single prostate-specific antigen (PSA) value is invariably associated with clinical metastasis or cancer-specific survival; PSA kinetics might prove to be a more important predictor of eventual progression-free survival and cancer-specific survival than absolute PSA level alone. With only one-third of patients progressing from biochemical recurrence to clinical disease, therapeutic morbidity should not outpace risk of disease progression. Salvage radiation therapy following radical prostatectomy has widely variable long-term biochemical control rates (from 18 to 64% depending on the follow-up period). Early hormonal therapy delivered as castration or complete androgen blockade might delay clinical metastasis in patients with high-risk pathologic disease; however, the adverse effects and morbidity of long-term therapy must not be underestimated. Non-steroidal antiandrogens as monotherapy for early biochemical recurrence, particularly for younger men who wish to preserve their libido and sexual potency, have received considerable attention, but there are conflicting data on long-term outcomes. Because of their favorable adverse-effect profiles, non-traditional therapies that exert localized hormonal or cellular effects are receiving considerable attention for treatment of early, PSA-only recurrence. Data from animal models provide a rationale for the use of these therapies, but there is a lack of evidence to support prolongation of progression-free survival or cancer-specific survival.

Cooperberg MR, Moul JW, Carroll PR. · Department of Urology, UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94115-1711, USA. · J Clin Oncol. · Pubmed #16278465 No free full text.

Abstract: Prostate cancer remains the most common noncutaneous human malignancy, and the second most lethal tumor among men. However, the natural history of the disease is often prolonged, and the survival benefits of local therapy for men with low-risk tumors may not be realized for a decade or more, as is increasingly well demonstrated in long-term observational cohorts in both the United States and Europe. A significant proportion of men with prostate cancer may be overdiagnosed, in the sense that diagnosis may not improve their lifespan or quality of life. However, the extent to which overdiagnosis represents a true problem relates to the consistency with which diagnosis leads invariably to active treatment. Prostate cancer is diagnosed at progressively earlier stages and with lower risk features; despite these trends, patients are less likely now than a decade ago to undergo a trial of active surveillance. Rates of brachytherapy and hormonal therapy use, in particular, have risen markedly. Important progress has been made in recent years in prostate cancer risk assessment. These advances, in combination with biomarkers in later stages of development, should be expected in the coming years to yield further improvements in clinicians' ability to diagnose prostate cancer early, and guide appropriately selected patients toward increasingly tailored treatment.

Moul JW, Saad F. · Division of Urological Surgery, Duke University Medical Center, Durham, NC 27710, USA. · Can J Urol. · Pubmed #16018829 No free full text.

Abstract: We currently lack a prospective, randomized, multicenter trial, to reassure low-risk prostate cancer patients, especially younger ones, that watchful waiting is a legitimate treatment. To better manage these patients, we need to: first, confirm that the patient has low-risk prostate cancer; second, adapt the treatment to the risk (i.e., if therapy is chosen over watchful waiting, it should be monotherapy not multiple therapy); third, be aware of age migration; fourth, know that radical prostatectomy and radiation were shown to be very effective for these patients at 10-year follow-up; and lastly, make an effort to better define watchful waiting and embrace it more, to avoid overtreatment.

Ward JF, Moul JW. · Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. · Clin Prostate Cancer. · Pubmed #15992460 No free full text.

Abstract: As increasing numbers of men are living longer with prostate cancer, larger proportions will eventually present to our collective practices with increasing prostate-specific antigen (PSA) levels. Such PSA relapses, conservatively estimated to affect approximately 50,000 men each year, have become the most common form of advanced prostate cancer. Salvage radiation therapy and salvage prostatectomy have important roles in our therapeutic armamentarium and should be valid options for young, healthy men. Counseling patients regarding expectations for cancer control and treatment morbidity has become better because of reports from larger series of patients who have had salvage radiation therapy and surgery. Some patients may not be appropriate candidates for salvage local therapies. A growing body of evidence suggests early hormonal therapy improves progression-free survival (PFS) and could alter cancer-specific survival. This benefit seems to be greatest when hormonal therapy is initiated while PSA levels are low, before clinically measurable disease becomes apparent. However, there is a cost to be paid in side effects and health care dollars when androgen deprivation is administered over prolonged periods. The nonsteroidal antiandrogen agent bicalutamide could offer PFS equivalent to that seen with castration without the complications of androgen deprivation. Observational data seem to indicate that individuals at high risk could also receive benefit from therapy administered before PSA detection. The potential opportunities for novel therapeutic agents with low associated morbidity are great.

Ward JF, Moul JW. · Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. · Curr Opin Urol. · Pubmed #15815196 No free full text.

Abstract: PURPOSE OF REVIEW: Through the prostate-specific antigen era, the proportion of men less than 55 years old with newly diagnosed prostate cancer more than doubled to almost 15%. As increasing numbers of men are living longer with prostate cancer, larger proportions will eventually present to our collective practices with rising prostate-specific antigen levels. Such prostate-specific antigen relapses, conservatively estimated to affect approximately 50 000 men each year, have become the most common form of advanced prostate cancer in the current period. RECENT FINDINGS: Increasing evidence suggests that early hormonal therapy improves progression-free survival and may alter the cancer-specific survival. However, there is a cost to pay in side-effects when androgen deprivation is administered over prolonged periods. The non-steroidal anti-androgen bicalutamide may offer an equivalent progression-free survival to castration without the complications of androgen deprivation. Observational data seem to indicate that high-risk individuals (i.e. those with high-grade, high-stage disease or a prostate-specific antigen doubling time less than 12 months) may also receive benefit from early therapy. SUMMARY: The definition of advanced prostate cancer has changed. Multimodal therapy improves cancer-specific outcomes especially in men with high-risk disease. The potential opportunities for novel therapeutic agents with low associated morbidity are great.

Ward JF, Moul JW. · Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. · Curr Opin Urol. · Pubmed #15815195 No free full text.

Abstract: PURPOSE OF REVIEW: The introduction of prostate-specific antigen into clinical practice heralded a dramatic shift in the epidemiology of prostate cancer. The diagnosis and treatment of lower stage disease in younger men with fewer competing co-morbidities has resulted in a longer period of post-treatment cancer surveillance and the potential for disease recurrence. Life-long periodic prostate-specific antigen testing for biochemical recurrence is standard of care; however, there is no single definition of biochemical recurrence that reliably predicts clinical recurrence. This review explores the complexities of biochemical recurrence, a thorough understanding of which is crucial to making appropriate treatment decisions after primary treatment. It also evaluates the array of diagnostic tests frequently employed when biochemical recurrence has occurred. RECENT FINDINGS: There is a disconnection between biochemical recurrence and progression to clinical disease. The definition of biochemical recurrence varies both by the prostate-specific antigen cut-point used and by the primary therapy employed. Furthermore, biochemical recurrence by itself appears not to be as reliable a predictor of eventual clinical recurrence as prostate-specific antigen doubling time. Current imaging modalities are rarely useful in localizing disease when biochemical recurrence is first detected. SUMMARY: The correct interpretation of biochemical recurrence is crucial to treatment decision-making. New data show that prostate-specific antigen doubling time during prostate-specific antigen recurrence may be a valid surrogate for death from the disease. The potential therefore exists for prostate-specific antigen doubling time to be accepted as a trial endpoint, which might accelerate drug approval by the United States Food and Drug Administration.