Conservative management of clinically localized prostate cancer

The purpose of this paper is to review and summarize the current knowledge on conservative management of localized prostate cancer. Deferring treatment for low-grade, clinically localized prostate cancer is an acceptable treatment option for patients with a life expectancy of 10-15 y or less. The outcome of available studies on deferred treatment in selected series cannot be compared with the outcome in register studies where the patients have been managed with noncurative intent, nor can it be directly compared with the outcome of selected series on other treatments. The outcome of different treatments for localized prostate cancer can only be compared in randomized studies.     

Current decision-making in prostate cancer therapy

PURPOSE OF REVIEW: Prostate cancer continues to be the most prevalent cancer among American men. Localized prostate cancer is commonly diagnosed because of improved screening practices nationwide. Several options exist for the treatment of localized prostate cancer, and this review discusses the decision-making process facing patients diagnosed with this disease. RECENT FINDINGS: No one treatment for localized prostate cancer has proven superior to date. For this reason patients have been found to use a number of resources to make an informed decision. These include physicians, spouses, family, friends, and different media. Urologists serve as the primary and most influential physicians and play an important role in the decision-making process. Patients, however, are assuming a more active role in this process as time evolves, especially with ease of access to multiple information resources. SUMMARY: In deciding on a treatment for localized prostate cancer, patients must weigh the risks and benefits of each option. Urologists must provide patients with up-to-date information on these options and be aware of the different influences that surround these men during the decision-making process.     

Quality of life in patients with localized prostate cancer

To date, there are no studies conclusively documenting that one treatment for localized prostate cancer is superior to another in terms of overall survival. Therefore, patients must consider other outcomes when choosing primary therapy for localized disease. One of the most important factors patients consider when choosing their treatment is the effect of therapy on their quality of life (QOL). Over the past decade, there have been an increasing number of studies assessing health related QOL (HRQOL) outcomes in localized prostate cancer. The goal of this article is to review our current understanding of HRQOL in this disease. We will begin by examining the established HRQOL instruments for use in localized prostate cancer. We will then discuss the effect of various treatments on QOL and review the literature comparing HRQOL outcomes between therapies.     

Scatter factor-hepatocyte growth factor elevation in the serum of patients with prostate cancer

PURPOSE: Scatter factor (SF), also known as hepatocyte growth factor (HGF), has been shown to induce proliferation, scattering and invasiveness in human prostate cancer cell lines. In this study we determined the serum level of SF-HGF in men with metastatic prostate cancer compared to those with localized prostate cancer and without prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from men with biopsy proved adenocarcinoma of the prostate and radiographic evidence of metastatic disease, those with biopsy proved adenocarcinoma of the prostate and clinically localized disease, and those with negative sextant prostate biopsies. Serum SF-HGF was determined using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: Of the 108 men enrolled in our study 52 had negative sextant biopsies, 36 had clinically localized cancer and 20 had metastatic disease. The serum level in men with metastatic disease was significantly elevated (mean 2,117 pg./ml., range 820 to 6,403) compared to that in men with localized cancer and without prostate cancer (mean 974 pg./ml., range 437 to 2,132 and 700, range 272 to 1,875, respectively, p = 9.5 x 10(-15)). Logistic regression analysis demonstrated that the association of ln (SF-HGF) with prostate cancer persisted after controlling for patient age and ln (prostate specific antigen) (p = 3.1 x 10(-4)). CONCLUSIONS: Serum SF-HGF is increased in men with metastatic prostate cancer. SF-HGF levels are associated with metastatic prostate cancer independent of the prostate specific antigen level and patient age. These data imply that SF-HGF may be an important serum marker for prostate cancer.     

Circulating biomarkers for prostate cancer

Due to its significant applicability for early detection, risk prediction and follow-up evaluation, prostate specific antigen (PSA) has revolutionized our ability to treat prostate cancer patients. With the prevalent use of PSA for early detection during the last two decades, disease characteristics have been altered towards early detected, localized tumors with a high chance of cure following local therapy. This advantage faces the risk of overdetection and overtreatment. In addition, PSA lacks both, sensitivity and specificity to accurately detect patients at risk of prostate cancer. Therefore, novel biomarkers are urgently needed to improve identification of men at risk of having the disease and to predict the natural behaviour of the tumor. Recent advances in the evaluation of high-throughput technologies have led to the discovery of novel candidate markers for prostate cancer. This article will briefly discuss current PSA-based strategies and review several novel biomarkers for prostate cancer, detectable in blood.     

Salvage prostate cryoablation for recurrent localized prostate cancer after radiotherapy

Salvage prostate cryoablation (SCA) for recurrent localized prostate cancer after radiotherapy has been studied in Western countries for more than a decade. We present our experience of SCA in a Taiwanese medical center. We performed four cases of SCA for recurrent localized prostate cancer after radiotherapy. The data recorded included age, cancer stage, prostate-specific antigen (PSA) level, Gleason score, prostate volume and patient outcome. The median follow-up period was 17 months. All cases were biopsy-proven to have residual cancer before cryoablation. After SCA, 25% of the patients reached undetectable PSA levels, 50% showed response but did not reach undetectable levels, and 25% showed no decrease in PSA. The median recurrence-free duration after SCA was 18 months in the patients who experienced a decrease in PSA. ADT was initiated after SCA for the patient who did not show any response, and bone metastasis was later diagnosed in that patient. Most patients experienced obstructive voiding problems after SCA, which improved over time. SCA is a safe salvage option for prostate cancer patients with local recurrence after RT. The preliminary results are encouraging. More extensive imagery to exclude extra-glandular disease is warranted before SCA. A longer follow-up period and larger sample size are necessary to delineate the benefits more conclusively.     

High-intensive focused ultrasound in localized prostate cancer

BACKGROUND AND PURPOSE: The results of the standard treatment for prostate cancer-radical prostatectomy-are not entirely satisfactory. A new local therapy, transrectal high-intensive focused ultrasound (HIFU), has been developed. We reviewed our experience with HIFU for palliation of localized prostate cancer. PATIENTS AND METHODS: Our series included 65 men with confirmed prostate cancer without detectable metastases who were not suitable candidates for radical prostatectomy. After prophylactic suprapubic cystostomy, the patients were treated using the Ablatherm version 2.32 under spinal anesthesia. The effects were monitored by serum prostate specific antigen assays, digital rectal examination, and biopsy. The mean follow-up is 10 months (range 1-18 months). RESULTS: There were no intraoperative or postoperative deaths, and there have been no deaths from prostate cancer. Residual cancer was detected in 35% of the patients in whom only biopsy-positive portions of the prostate were treated and 17% of those in whom the entire gland was treated. Retreatment was performed 1 month after the first session in these patients. The prostate volume increased an average of 30% after treatment, but by 3 months, the gland was 10% to 20% smaller than its original size. Three patients suffered complications secondary to overheating of the rectal wall or treatment too close to the external urethral sphincter. CONCLUSION: The low morbidity, minimal invasiveness, avoidance of systemic side effects, and potentially curative effect make HIFU a potentially useful option for the treatment of localized prostate cancer.     

Techniques, indications and results of permanent prostate brachytherapy for localized prostate cancer

Permanent seed brachytherapy as a monotherapy is an appropriate treatment in patients with low risk localized prostate cancer such as intraprostatic cancer, T1-2 stage, PSA less than 10 ng/mL, low tumour volume, well differentiated cancer (Gleason score less than 7), gland size less than 50 mL, no micturition symptoms that could decompensate after implantation. A brachytherapy program needs a specialized multidisciplinary team with the collaboration of urologists, radiotherapists (authorized person to manipulate radioactive elements), and physicists. The 10-year oncologic and morbidity results have been published in the literature and are comparable to those of other standard treatments of localized prostate cancer such as radical prostatectomy and external beam radiation therapy.     

The physical burden of prostate cancer

The physical burden of prostate cancer is considerable and affects quality of life in men with both localized and metastatic disease. This physical impact results as much from treatment for prostate cancer as from the disease itself. In advanced disease, although patients can experience considerable pain and discomfort from bony lesions, they also can experience bothersome fatigue and sleep disturbances from institution of hormone ablation therapy. In localized disease, although patients can have lower urinary tract symptoms from untreated prostate cancer, all aggressive treatments can result in urinary, sexual, and bowel dysfunction that can bother the patient and affect quality of life. Patients and providers must be vigilantly aware of the physical burden of prostate cancer when initiating treatment for this disease and during follow up after treatment. By being cognizant of the physical impact of prostate cancer on quality of life, providers can address patients' problems early in their course of treatment and maximize patients' HRQOL and overall satisfaction with care.     

Principles and results of high-intensity focused ultrasound for localized prostate cancer

Focused ultrasound holds promise in a large number of therapeutic applications. It has long been known that high-intensity focused ultrasound (HIFU) can kill tissue through coagulative necrosis. However, it is only in recent years that practical clinical applications are becoming possible, with the development of high-power ultrasound arrays and noninvasive monitoring methods. In the last decade, HIFU have been adapted and used to treat localized prostate cancer and it is now commercially available in Europe. In this article, preclinical studies and clinical development of prostate HIFU as well as early clinical results from our center and international studies are reviewed. Early results demonstrated that prostate HIFU is efficient to obtain local control for low- and intermediate-risk localized prostate cancer; however, long-term follow-up is still needed to estimate the efficacy of prostate HIFU in terms of specific cancer mortality. This makes HIFU a viable alternative in patients not candidate for radical therapy.     

Neuroendocrine differentiation of localized prostate cancer during endocrine therapy

A 74-year-old male was treated with endocrine therapy for localized prostate cancer. After 25 months he complained of a swollen neck, and was diagnosed with prostate cancer with lymph node metastasis of neuroendocrine differentiation. Neuroendocrine differentiation without elevation of conventional tumor markers is rare during the initial recurrent course of localized prostate cancer.     

Current status of endocrine therapy in localized prostate cancer: cure has become a strong possibility

It is clear that all available means should be taken to diagnose prostate cancer early and to use efficient therapy immediately in order to prevent prostate cancer from migrating to the bones where treatment becomes extremely difficult and cure or even long-term control of the disease is an exception. The only means of preventing prostate cancer from migrating to the bones and becoming incurable is efficient treatment at the localized stage of the disease. In fact, since radical prostatectomy, radiotherapy and brachytherapy can achieve cure in about 50% of cases, these approaches are all equally valid choices as first treatment of localized prostate cancer. However, in view of the current knowledge and available data, nowadays, androgen blockade should also be considered as first line treatment. While showing the high efficacy of hormonal therapy in localized prostate cancer, present knowledge clearly indicate that long-term treatment with the best available hormonal drugs, somewhat similar to the 5 years of Tamoxifen in breast cancer, is required for optimal control of prostate cancer. It is also clear from the data analyzed that combined androgen blockage alone could well be an efficient therapy of localized prostate cancer while it has already been recognized as the best therapy for metastatic disease. This paper presents and discusses the current knowledge available on the use and results of endocrine therapy in localized prostate cancer.     

Reliability of death certificates in prostate cancer patients

Objective. To evaluate the reliability of cause-of-death diagnoses among prostate cancer patients. Material and methods. Information from death certificates obtained from the Swedish Death Register was compared with systematically reviewed medical records from the population-based Swedish Regional Prostate Cancer Register, South-East Region. In total, 5675 patients were included who had been diagnosed with prostate cancer between 1987 and 1999 and who had died before 1 January 2003. Results. The proportion of prostate cancer cases classified as having died from prostate cancer was 3% higher in the official death certificates than in the reviewed records [0.03, 95% confidence interval (CI) 0.02 to 0.04]. Overall agreement between the official cause of death and the reviewed data was 86% (95% CI 85 to 87%). A higher accuracy was observed among men with localized disease (88%, 95% CI 87 to 89%), aged 60 years or younger at death (96%, 95% CI 93 to 100%), or who had undergone curative treatment (91%, 95% CI 88 to 95%). This study indicates a relatively high reliability of official cause-of-death statistics of prostate cancer patients in Sweden. Conclusion. Mortality data obtained from death certificates may be useful in the evaluation of large-scale prostate cancer intervention programmes, especially among younger patients with localized disease.     

EAU guidelines on prostate cancer

OBJECTIVES: The first summary of the European Association of Urology (EAU) guidelines on prostate cancer was published in 2001. These guidelines have been continuously updated since many important changes affecting the clinical management of patients with prostate cancer have occurred over the past years. The aim of this paper is to present a summary of the 2005 update of the EAU guidelines on prostate cancer. METHODS: A literature review of the new data has been performed by the working panel. The guidelines have been updated and level of evidence/grade of recommendation added to the text. This enables readers to better understand the quality of the data forming the basis of the recommendations. RESULTS: A full version is available at the EAU Office or at . Systemic prostate biopsies under ultrasound guidance is the preferred diagnostic method and the use of periprostatic injection of a local anaesthetic can significantly reduce pain/discomfort associated with the procedure. Active treatment (surgery or radiation) is mostly recommended for patients with localized disease and a long life expectancy with radical prostatectomy being the only treatment evaluated in a randomized controlled trial. Follow-up is at large based on prostate specific antigen (PSA) and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy has become an option for selected patients with hormone refractory prostate cancer. CONCLUSION: The knowledge in the field of prostate cancer is rapidly changing. These EAU guidelines on prostate cancer summarize the most recent findings and put them into clinical practice.     

Expectant management: an option for localized prostate cancer

Localized prostate cancer demonstrates tremendous heterogeneity in the natural history of the disease. To this end, although prostate cancer may be present histologically in nearly 30% of all men above the age of 50 y, the lifetime risk of developing clinically significant disease is 18% (one in six). Furthermore, the lifetime risk of dying from prostate cancer is less than 4%. Therefore, in order to avoid unnecessarily treating potentially insignificant prostate cancer, the concept of expectant management has been considered for this disease. In this brief review, we discuss the evolution of expectant management for men with localized prostate cancer.     

Neodymium-YAG laser in the treatment of localized prostate cancer

The combination of transurethral resection and subsequent Neodymium-YAG laser irradiation has been practiced for radical treatment of localized prostate cancer since 1981. One hundred and eighteen patients have been treated and the observation time ranges 6-98 months. The treatment is performed endoscopically in two separate steps. The procedure is simple and complications are few. One hundred and four patients are evaluated as disease-free survivors. The overall actuarial disease-free survival rate is 88% in the 4-8 year period. The results compare satisfactorily with results obtained by other methods. Recently published results from other clinics confirm the laser to be promising in the treatment of localized prostate cancer.     

Measuring the quality of care for localized prostate cancer

PURPOSE: We describe the current status of quality of care measurement for localized prostate cancer and provide a framework for preserving a leadership role for our specialty in this dynamic and controversial field. MATERIALS AND METHODS: Basic methodological principles of quality of care assessment were reviewed. Several factors that suggest the potential for current variation in the quality of care for patients with localized prostate cancer, particularly those receiving active treatment, were then analyzed. Subsequently contemporary publications and investigations that comprise the current foundation of prostate cancer quality of care research were reviewed. RESULTS: The foundation for much of the emerging research in prostate cancer quality of care assessment is based on the Donabedian structure-process-outcome paradigm. The RAND candidate quality indicators for localized prostate cancer were developed in this framework and they represent the first effort to systematically consider the measurement of quality as it relates to prostate cancer. The feasibility of applying the RAND quality indicators to clinical quality of care assessments has been demonstrated, although further modification and refinement of the indicator set are necessary prior to large-scale, population based implementation of these quality assessment measures. Moreover, future quality of care efforts must make the transition to primarily prospective or concurrent quality assessments, such that measures can be taken to modify the structure and/or process of care at the time of delivery or shortly thereafter. CONCLUSIONS: Prostate cancer quality of care assessment represents a burgeoning domain of urological health services research. To date such initiatives have come from within and outside of our specialty. In the future such efforts are likely to expand and they may have a substantial impact on the clinical and administrative aspects of urological practice. As a result, urologists should maintain a leading role in efforts to further define of quality of care as it relates to prostate cancer and radical prostatectomy.     

Interstitial microwave thermoablation for localized prostate cancer

The conventional treatment for localized prostate cancer can be associated with significant morbidity and cost. Interstitial microwave thermoablation is a minimally invasive procedure used experimentally to treat selected patients with failed radiation therapy of prostate cancer at our institution. Preliminary results in these patients suggest that this treatment might be a useful alternative in selected patients with previously untreated localized prostate cancer. In this report we describe the first use of percutaneous transperineal interstitial microwave thermoablation to treat a case of primary prostate cancer. There were no treatment complications. At 18 months the patient's serum prostate-specific antigen remains undetectable, and his prostate biopsy shows no evidence of malignancy. These very preliminary but exciting results in this single patient suggest that this experimental technique should be explored further.     

Next generation patient-derived prostate cancer xenograft models

There is a critical need for more effective therapeutic approaches for prostate cancer. Research in this area, however, has been seriously hampered by a lack of clinically relevant, experimental in vivo models of the disease. This review particularly focuses on the development of prostate cancer xenograft models based on subrenal capsule grafting of patients＇ tumor tissue into nonobese diabetic/ severe combined immunodeficient （NOD/ SCID） mice. This technique allows successful development of transplantable, patient-derived cancer tissue xenograft lines not only from aggressive metastatic, but also from localized prostate cancer tissues. The xenografts have been found to retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, response to androgen ablation and metastatic ability. As such, they are highly clinically relevant and provide valuable tools for studies of prostate cancer progression at cellular and molecular levels, drug screening for personalized cancer therapy and preclinical drug efficacy testing; especially when a panel of models is used to cover a broader spectrum of the disease. These xenograft models could therefore be viewed as next-generation models of prostate cancer.     

Screening and early hormonal treatment of prostate cancer are accumulating strong evidence and support

BACKGROUND: I review the data published during the last 5 years on the effects of early treatment of prostate cancer on survival. METHODS: Data from prospective and randomized studies as well as from population-based studies are presented. RESULTS: Two studies (European Organization for Research and Treatment of Cancer and Radiation Therapy Oncology Group) in stage T3 disease have shown that long-term (3 years or indefinite, respectively) androgen blockade prolongs life in patients receiving androgen blockade in addition to radiotherapy compared to radiotherapy alone. In the UK Medical Research Council study, androgen blockade at diagnosis of locally advanced or asymptomatic patients decreased cancer-specific death by 21% compared to delayed treatment. A 69% decrease in prostate cancer death was observed in the Quebec Randomized Prostate Cancer Screening Study. Population-based studies in Sweden and Denmark have shown that 62% and 63%, respectively, of patients diagnosed with localized prostate cancer will die from the disease if not treated immediately. Decreases in prostate cancer death rate of 6.3-23% have been found between 1991-1997 in the US and Canada, respectively. CONCLUSIONS: Treatment of localized disease has been shown in all the available randomized studies to cause a marked decrease in prostate cancer death. Simple use of the available screening procedures and treatments for localized prostate cancer could cause a dramatic decrease in prostate cancer death.