Hoch intensiver fokussierter transrektaler Ultraschall (rHIFU) zur lokalen Therapie des Prostatakarzinoms

Pulsed robotic high-intensity focused ultrasound (rHIFU) is an interesting therapeutic option mainly due to its noninvasive character. In urologic oncology, rHIFU is used for the transrectal therapy of prostate cancer. While percutaneous therapy of renal cancer using rHIFU is still being tested in experimental studies, transrectal therapy with rHIFU for prostate cancer is already established in more than 230 urologic departments worldwide. The results of prostate cancer therapy with rHIFU are mainly based on different clinical studies. In 2007 a clinical study comparing rHIFU and cryotherapy for the treatment of prostate cancer was initiated in the USA in order to gain clinical approval by the FDA. The most recent publications concluded that the use of rHIFU is an effective standard treatment for prostate cancer with a broad range of indications in all tumor stages: (1) in the primary treatment of local prostate cancer, (2) in patients with local recurrence after failure of any primary treatment, and (3) as an adjuvant therapy in the palliation of systemic prostate cancer.     

Contemporary use of hormonal therapy in prostate cancer: managing complications and addressing quality-of-life issues

While both short- and long-term androgen deprivation therapy (ADT) are effective for treating prostate cancer, with the clinical benefits patients can often have significant side-effects. It is important that these complications are recognized and managed appropriately so that adverse effects on the patient's quality of life (QoL) are minimized. The incidence of deaths from prostate cancer has decreased over the last decade, probably as a result of various factors including improved screening and diagnosis, improved treatments, and better risk assessment to help guide therapy. A meta-analysis of prostate cancer trials comparing the use of early vs late hormonal therapy found that 10-year overall survival increased by up to 20% between 1990 and 2000, and this was attributed to the earlier use of hormone therapy (HT) in these patients. Data from the USA Cancer of the Prostate Strategic Urological Research Endeavor database also suggest a significant decrease in risk in the last two decades in the USA, with more patients being identified with low-risk disease at diagnosis. In addition, there has been an increase in recent years in the use of HT at all stages of prostate cancer. The extensive use of ADT has raised concerns about potential adverse effects. ADT might be associated with a range of adverse effects that vary in their degree of morbidity and effect on the patient's QoL. They include hot flashes, osteoporosis, loss of libido or impotence, and psychological effects, e.g. depression, memory difficulties or emotional lability. Effective strategies are available for managing the major side-effects of HT, but to many patients these unwanted effects are often less important than the benefits of treatment. An investigation of health-related QoL found that men with prostate cancer receiving ADT had a poorer QoL than those not receiving ADT, but the difference was less pronounced after controlling for comorbidities. Many new therapies are currently under investigation which aim to maximize the clinical effects of ADT while reducing the adverse effects.     

Clinical trials in patients with biochemically relapsed prostate cancer

In this section there is a wide diversity of mini-reviews, covering several areas of interest for readers. Authors from the USA write about clinical trials in patients with biochemically relapsed prostate cancer, again bridging the divide between medical oncologists and urologists who specialise in urological oncological surgery. The second paper is a joint one from Germany and the USA, bringing the reader up to date with advances in the treatment of stress urinary incontinence. Finally there are two papers from Australia describing the use of positron emission tomography in renal cancer and in prostate cancer.     

Nonaggressive management of White and Black prostate cancer patients in the United States

Appropriate treatment for prostate cancer is controversial because of the lack of information from randomized clinical trials indicating the benefits of one treatment over another. Watchful waiting or conservative management remains an alternative for this disease. This paper assesses the extent to which White and Black prostate cancer patients in the USA choose nonaggressive therapy. Nonaggressive therapy is defined as patients not receiving cancer-directed surgery or radiation, or that undergo a transurethral resection of the prostate (TURP)/simple prostatectomy but no radiation. Of 112,445 prostate cancer patients diagnosed in 1992-1996, 40% Whites and 46% Blacks were not aggressively treated. Approximately 28% Whites and 33% Blacks did not receive cancer-directed surgery or radiation, and 12% Whites and 13% Blacks underwent a TURP/simple prostatectomy but no radiation. Stage, histologic grade and age at diagnosis, race (White and Black), and number of cancer primaries each significantly influence how patients are managed. Black patients are more likely than White patients to forego aggressive therapy, even after adjusting for less preferential stage and histologic grade at diagnosis, as well as differences in age and number of cancer primaries. Explanations for this result deserve further consideration. Prostate Cancer and Prostatic Diseases (2000) 3, 94-99     

Active surveillance and radical therapy in prostate cancer: can focal therapy offer the middle way?

Introduction  Focal therapy for prostate cancer is a radical paradigm shift in the management of men with localised prostate cancer. It involves locating and destroying only the areas of prostate cancer whilst leaving the majority of the prostate untreated. By doing so, it is proposed that side-effects of traditional whole-gland therapies such as impotence, incontinence and rectal toxicity will be significantly reduced and cancer control will be at similar levels. Methods and materials  A Medline/Pubmed search was conducted between 1 May 1998 and 1 May 2008 using the following terms: 'focal therapy', 'lumpectomy', 'hemiablation', 'laterality', 'multifocal', 'unifocal' and 'index lesion' alongside 'prostate cancer'. Articles were selected for their relevance to this review. Abstracts from international conferences over the last 5 years were also used where appropriate. Authors' personal bibliography was used to supplement the review. Conclusions  A number of case series have reported significantly lower incontinence and impotence rates using focal cryoablation and one series on focal HIFU. The reporting quality has been variable and there are currently ongoing clinical trials with IRB approval in the USA and UK. Long term follow-up is required. Focal therapy is an exciting new area of research that could hold great promise for men with localised low to intermediate risk prostate cancer.     

Updated Japanese Urological Association Guidelines on prostate‐specific antigen‐based screening for prostate cancer in 2010

The exposure rate of screening for prostate cancer using prostate‐specific antigen (PSA) in Japan is still very low compared with that in the USA or western Europe. The mortality rate of prostate cancer will increase in the future and in 2020 it will be 2.8‐fold higher than in 2000. Therefore, there is an urgent need to determine the best available countermeasures to decrease the rate of prostate cancer death. PSA screening, which can reduce the risk of death as a result of prostate cancer, should be offered to all men at risk of developing prostate cancer with fact sheets showing updated benefits and drawbacks of screening for prostate cancer.     

Carbonic anhydrase IX and the future of molecular markers in renal cell carcinoma

The use of carbonic anhydrase IX as a promising molecular marker in RCC is described by authors from Los Angeles, who discuss the promise that molecular markers hold to improve diagnosis, staging, treatment, surveillance and survival of patients with RCC. There is a whole range of new treatments being introduced in the management of metastatic renal cancer. The use of VEGF-targeted therapy has particular importance, especially as it has a strong genetically linked rationale for its potential success in this area. Authors from the USA show that substantial clinical activity has been reported in initial clinical trials. In prostate cancer, drugs targeting microtubules, such as taxanes, have already been introduced clinically, and their success has received widespread attention. A new group of drugs, the epothilones, have similar but not identical binding properties to microtubules, and authors from the USA describe how they have shown activity in hormone-refractory prostate cancer, and are moving to phase III testing.     

Japanese Urological Association guidelines on prostate‐specific antigen‐based screening for prostate cancer and the ongoing cluster cohort study in Japan

The exposure rate of screening for prostate cancer using prostate‐specific antigen (PSA) in Japan is still very low compared with that in the USA or Western Europe. The mortality rate of prostate cancer will increase in the future and in 2020 it will be 2.8 times higher than in 2000. Therefore, there is an urgent need to determine the best available countermeasures to decrease the rate of prostate cancer death.     

Improving the Risk–Benefit Ratio of Endocrine Therapy in Prostate Cancer

ContextUntil very recently, it was known that endocrine therapy could improve progression-free survival but few studies could demonstrate a survival advantage in patients treated with early endocrine therapy.ObjectivesTo summarise indications and outcomes of endocrine therapy in prostate cancer and to review the different ways of reducing side-effects from this treatment modality.Evidence acquisitionSeveral randomised and nonrandomised clinical trials that deal with endocrine therapy for prostate cancer, its benefits, and its side-effects and that were published in the English literature were reviewed.Evidence synthesisAdjuvant endocrine therapy after local therapy for localised prostate cancer (T1-2 N0 M0) offers no survival advantage and has many side-effects. Treatment of locally advanced prostate cancer (T3-4 N0 M0, T1-4 N1 M0) with early androgen deprivation only has also been shown not to be superior to deferred androgen deprivation in either overall or prostate cancer-specific survival. In locally advanced prostate cancer, either radical prostatectomy or radiotherapy must be included to gain benefits from early androgen deprivation. Patients with prostate-specific antigen (PSA) relapse after local therapy for localised prostate cancer constitute a very specific group. PSA doubling time and tumour differentiation offer the opportunity to select different patient subgroups for endocrine therapy. In short-term analyses, intermittent androgen suppression seems to have fewer side-effects with equal effectiveness in cancer control; however, there are no data for either overall or prostate cancer–specific survival. Some side-effects of prolonged androgen suppression can be prevented with adjuvant medication. Biphosphonates have been demonstrated to prevent bone loss, while oestrogen receptor modulators, such as toremifene citrate, seem to alleviate side-effects such as bone metabolism, altered lipid profile, and hot flushes.ConclusionsEndocrine therapy is indicated in specific patient subgroups. Treatment strategies and adjuvant medication help to diminish treatment-associated toxicity.     

Iodine seed prostate brachytherapy: an alternative first-line choice for early prostate cancer

This article on permanent iodine-125 seed prostate brachytherapy reviews the techniques, results, and patient selection issues for early prostate cancer. The long-term 10 y results of brachytherapy from Seattle, and their reproducibility in other centres both in the USA and UK are reported. The use of hormone therapy in brachytherapy and the value of combining external beam radiotherapy with a brachytherapy implant are discussed. Reviewed comparative data show the similarity of biochemical survival in patients treated with brachytherapy, radical prostatectomy, and external beam radiotherapy. The role of brachytherapy as a first-line treatment option for patients with prostate cancer is demonstrated.     

The rising prevalence of androgen deprivation among older American men since the advent of prostate-specific antigen testing: a population-based cohort study

OBJECTIVE: To investigate the effect of efforts in the early detection of prostate cancer using prostate-specific antigen (PSA) testing in the USA, by estimating the regional prevalence of androgen deprivation therapy (ADT) among older men in 1993-2000, and correlating the prevalence with early detection and aggressive treatment rates in 1987-91, as some authors predicted that ADT, a treatment traditionally reserved for advanced prostate cancer, would become less common over time as a result of such efforts. PATIENTS AND METHODS: A sample of 5% of men who were Medicare beneficiaries was used in this prospective population-based cohort study. The main outcome measures were the overall prevalence of ADT (medical and surgical) in the cohort from 1993 to 2000, and correlations between rates of prostate procedures in the 306 USA hospital referral regions in 1987-91 and prevalence of ADT in those regions from 1993 to 2000. RESULTS: The prevalence of ADT among these men in the USA increased steadily from 1.8% in 1993 to 2.9% in 2000 (P < 0.001). Regions with higher rates of prostate biopsy in 1987-91 had a higher prevalence of ADT in 1993, 1995 and 1997 (P < 0.05). Regions with higher rates of transurethral prostatectomy in 1987-91 had a higher prevalence of ADT in 1993-2000 (P < 0.01). Regions with higher rates of radical prostatectomy in 1987-91 had higher rates of ADT in 1993-99 (P < 0.05). CONCLUSIONS: Widespread early detection and aggressive treatment for prostate cancer in the USA has been associated with more, not less, ADT among older men over time.     

The role of lymphadenectomy in high risk prostate cancer

Historically, patients with high risk prostate cancer were considered poor candidates for radical prostatectomy (RP) due to the likelihood of positive pelvic lymph nodes and decreased long term survival. Although there is still no consensus on the optimal therapy for this group of patients, there is increasing evidence that surgery could play a role. Cancer specific survival (CSS) rates after RP for locally advanced disease at 10 year follow up range from 29 to 72%, depending on tumor differentiation. The role of pelvic lymph node dissection (PLND) in prostate cancer remains a controversial topic. Nonetheless, in conjunction with RRP extended PLND (ePLND) should be performed as extended lymph node dissection in lieu of standard PLND may increase staging accuracy, influence decision making with respect to adjuvant therapy and possibly impact outcome. High risk patients with organ confined prostate cancer and low volume (micro)metastatic disease may be the ones to profit most from this approach.     

The timing of hormone therapy for men with asymptomatic advanced prostate cancer

The most appropriate time to introduce hormonal therapy for patients with advanced prostate cancer is a contentious issue. Recent prospective studies comparing immediate and deferred hormonal therapy (medical or surgical castration) on survival outcome are reviewed with the aim of redefining the most appropriate time to initiate hormonal therapy for individual patients. The evidence supports the use of immediate hormonal therapy in previously untreated patients with advanced disease (M1) and also the use of adjuvant hormonal therapy after radical prostatectomy and lymphadenectomy for node-positive (but clinically localized) disease. Immediate hormonal therapy may also be advantageous in advanced local/regional disease when it is the primary treatment contemplated (i.e., without any definitive curative therapy to the prostate), although not all studies show this. Adjuvant hormonal therapy has significantly improved survival in some studies in the radiotherapy setting; the lack of statistically significant benefits in other studies may be a result of the timing of hormonal therapy in relation to the administration of external beam irradiation. Decisions on the immediate initiation of hormonal therapy should also take into account the patient's life expectancy and the side effects and long-term complications of androgen deprivation therapy. Recent epidemiological studies indicate that prostate cancer mortality has fallen in the USA. This decline in prostate cancer mortality is likely to be multifactorial with early application of hormonal therapy being one potential contributory factor. It is recommended that after an assessment of their disease risk, patients should be informed about the benefits and side effects of all potential treatment options and allowed to make an informed choice about their treatment.     

The role of systemic cytotoxic therapy for prostate cancer

Prostate cancer is among the most common types of cancer and cause of cancer‐related deaths among men in the USA and Europe. Despite improvements in early detection and treatment for localized disease, many patients still present with advanced disease, or attempted curative local therapy fails. Although hormone therapy is successful initially in the vast majority of patients, most develop hormone‐refractory prostate cancer (HRPC) after 18–24 months. In the past, the use of chemotherapy in the management of prostate cancer has been limited, but recent evidence of its efficacy in HRPC has prompted further research to determine if it could have a more extensive role in the treatment of this disease. Data from several studies have highlighted the possible beneficial effects of incorporating chemotherapeutic agents in treatment regimens for HRPC, showing evidence of a survival advantage. One of the goals of research now is to determine optimal management strategies for different patient populations with prostate cancer. Preliminary data suggest that further improvements in efficacy might be achieved with multi‐agent chemotherapy or by treating patients earlier in the disease process.     

Prostate brachytherapy

In recent years there has been an increase in the number of centres, especially in the USA, using prostate brachytherapy as a means of treating localised prostate cancer. Several centres now have medium term follow up data of large numbers of patients treated with this technique suggesting that outcome in terms of tumour control may be comparable to patients treated surgically. This review summarises results from different brachytherapy series and outlines some of the possible advantages of this technique compared with current conventional treatments for localised prostate cancer.     

Patient Selection for Therapy in Prostate Cancer

The two major challenges in prostate cancer today are biochemical failure and hormone-refractory disease. Biochemical failure, manifested by a rising prostate-specific antigen (PSA) level following failure of local therapy, is the most common presentation of advanced prostate cancer. Hormonal therapy can produce dramatic but short-lived response rates in metastatic hormone-sensitive prostate cancer, while chemotherapy possesses the ability to induce significant response rates in refractory disease. Clinicians agree that patients with symptomatic advanced prostate cancer should receive immediate androgen ablation therapy; however, there is debate regarding treatment for asymptomatic patients with advanced disease. While there is no clear evidence to support the widespread use of aggressive interventions such as hormonal therapy with or without chemotherapy in men with biochemical failure, there are a number of studies indicating that early hormonal therapy may prolong the time to disease progression and survival for some patients, with this benefit being more pronounced in men with less tumor burden. Numerous questions remain for patients with advanced prostate cancer regarding optimal therapy, and until these questions are answered, the use of early hormonal therapy with or without chemotherapy for the management of locally advanced and metastatic disease is warranted.     

Focal Therapy Will Be the Future Treatment Modality: The Motion “Con”

This is a special edition publication examining the merits and disadvantages of focal therapy to treat prostate cancer. Although several publications have already dealt with this topic, outlining the benefits of several novel techniques to treat prostate cancer, in this paper we focus on the argument from the “con” perspective and outline the rationale for why focal therapy as an approach to treat prostate cancer with current technologies is suboptimal. We provide the basis for this reasoning, discussing four focal treatment modalities; namely, high-intensity focused ultrasound, cryotherapy, radio frequency ablation, and photodynamic therapy. Given that none of the focal treatment options is without potential morbidity or mortality, that current technological limitations prevent complete mapping of the prostate and subsequent identification and treatment of all lesions, and that there is still significant potential for residual disease after focal treatment, we feel that a subset of men with favourable disease parameters who do not want definitive treatment may be better suited to undergo the less morbid treatment option, active surveillance.     

The pharmacokinetics of fosfestrol and diethylstilbestrol in chronic hemodialysis patients with prostate cancer

BACKGROUND: Fosfestrol drip infusion therapy is an available endocrinotherapy for prostate cancer. But since there have been few reports of its use in chronic dialysis patients, the pharmacokinetics of fosfestrol in these patients remains unclear. We conducted fosfestrol drip infusion therapy as an induction therapy in chronic hemodialysis patients with prostate cancer. METHODS: Two male patients were included in this study. One was a 68-year-old man who had been in hemodialysis for 15.7 years and had stage B2 prostate cancer. The other was a 74-year-old man who had been in hemodialysis for 4.4 years and had stage C prostate cancer. A total of 250 mg of fosfestrol was dissolved in 250 mL of 5% glucose solution and administered by drip infusion. The drug was given subcutaneously during 14 consecutive days and a luteinizing hormone-releasing hormone agonist was injected on day 15. RESULTS: Serum fosfestrol levels increased rapidly after the drip infusion was started and remained at high levels during infusion, but fell quickly after the treatment ended. Diethylstilbestrol (DES) was also detected in blood after the infusion was started and its levels peaked when infusion ended. But on the next day, neither fosfestrol nor DES were detected in the blood of the patients. Moreover, neither fosfestrol nor DES was detected in the blood of the two patients before administering fosfestrol on day 15. Fosfestrol was quickly eliminated from the blood after hemodialysis was started, while DES remained in the blood during hemodialysis. The adverse reactions were mild hepatic dysfunction and gynecomastia. CONCLUSIONS: Fosfestrol drip infusion therapy appeared to be safe as an endocrinotherapy for prostate cancer in chronic hemodialysis patients.     

前列腺癌的流行病学特征及晚期一线内分泌治疗分析

目的 分析北京、上海、广州的三个中心前列腺癌的流行病学特征,初步反映中国发达地区的前列腺癌现状.对晚期前列腺癌患者内分泌治疗相关资料进行分析,寻找内分泌治疗效果以及生存预后的预测因子.方法 收集三个中心525例前列腺癌患者的临资料,进行流行病学分析.并对其中272例资料完整的晚期前列腺癌患者的内分泌治疗效果以及生存预后进行分析.结果 68.0%的患者确诊时已属于晚期,80.2%的患者以内分泌治疗为主要治疗手段.Gleason分值、有无骨转移和血清前列腺特异性抗原最低点是晚期前列腺癌疾病进展的独立预后因子.结论 绝大多数患者在确诊时已经为疾病晚期,内分泌治疗是主要治疗方法.Gleason分值、有无骨转移和PSA最低点是晚期前列腺癌疾病进展的独立预后因子.     

Patterns and trends in prostate cancer incidence,survival, prevalence and mortality. Part I: international comparisons

The international patterns and trends in prostate cancer incidence, survival, prevalence and mortality were examined. Age-standardized incidence and death rates among men in a variety of countries worldwide were obtained from various sources, survival rates from European sources and elsewhere, and prevalence estimates from the EUROPREVAL study. Results from many published studies were summarized. The incidence of prostate cancer varies widely around the world, with by far the highest rates in the USA and Canada. There has been a gradual increase in the incidence of prostate cancer since the 1960s in many countries and in most continents; there were large increases in the late 1980s and early 1990s in the USA, but increases have also occurred in countries with comparatively low incidence, e.g. India. Survival from prostate cancer improved during the 1970s and 1980s; further increases in the 1990s may be largely a result of earlier diagnosis. There were wide differences in survival across Europe, with rates in the UK well below the average, but all European rates were far below those in the USA. There was wide variation in the prevalence of prostate cancer in Europe; in some countries with high incidence and high life-expectancy, prostate cancers formed approximately 15% of all prevalent cancers in men. Mortality from prostate cancer has also increased in many countries, but to a lesser extent than incidence; this is consistent with the observed trends in survival. Mortality decreased slightly in the mid to late 1990s in several countries, including the USA, Canada, England, France and Austria. Part of the apparent increases in the incidence of prostate cancer has been associated with diagnostic artefacts (particularly detecting preclinical tumours through the increased use of transurethral resection) which may also have had an effect on death certification through the incorrect attribution of prostate cancer as the underlying cause of death. However, the greatest effect on the registration of new cases of prostate cancer has been the increased availability of prostate specific antigen testing during the early- to mid-1990s. Possibly, in addition to the effect of attribution bias, the earlier diagnosis of prostate cancers has contributed to the recent slight decreases in mortality. However, this is unlikely to account for much of the reduction, given the slow development of the disease from onset to death. Changes in disease management are probably more important. There are many strong arguments against introducing population-based screening for prostate cancer.