Molekulare multimodale Hybridbildgebung des Prostata- und Blasenkarzinoms

Since the introduction of combined radiologic-nuclear imaging procedures like PET/CT and PET/MRI, new and promising diagnostic tools in bladder and prostate cancer imaging are available to physicians. Although PET-based hybrid imaging in bladder cancer is currently utilized only in selected cases, an increase in PET imaging can be observed in prostate cancer due to the development of cancer-specific PET tracers. Especially novel ligands of prostate-specific membrane antigen (PSMA) exhibit great potential to effectively influence future staging of prostate cancer. However, before recommendations for implication in routine staging can be given, evaluation in the context of prospective multicenter clinical trials are mandatory.     

Management of radiation failure for localized prostate cancer

Due to the historically large number of patients with localized prostate cancer (CAP) treated by radiation therapy, an increasing number of patients are presenting local failure. The currently available concepts regarding its definition as well as management options are reviewed. The literature regarding radiation failure for localized prostate cancer was reviewed. Emphasis was made on articles concerning definition of radiation failure, patient evaluation and restaging and definitive as well as palliative management options. There is definitely a subset of patients with locally recurrent prostate cancer without evidence of metastasis that could potentially benefit from aggressive local therapy. A treatment algorithm is proposed but it should be emphasized that treatment options should be individualized to suit the need of a particular patient.     

Locally advanced prostate cancer: the role of surgical management

Among the heterogeneous population of patients with prostate cancer, a high‐risk group with locally advanced prostate cancer (LAPC) present a diagnostic and therapeutic dilemma. Although the incidence of LAPC has decreased with screening since the introduction of prostate‐specific antigen (PSA) testing, significantly many patients are still diagnosed with LAPC. These patients are by definition at higher risk of metastatic disease and worse outcomes. The role of radical prostatectomy (RP) in this population has been debated, as the combination of radiotherapy and hormonal therapy is becoming used more frequently for LAPC. Unfortunately, the clinical staging and evaluation of LAPC is a challenge that results in possibly understaging or overstaging these patients. This further complicates therapeutic decision‐making, and as a result no established standard treatment has been proposed. Like other patients with prostate cancer, individualized therapeutic choices are essential and depend on a multitude of factors. Herein we examine the role of RP for managing LAPC and attempt to emphasize how the risk of distant disease and difficulty with clinical staging might favour incorporating a surgical approach as part of the therapy for patients with LAPC.     

Molecular markers in prostate cancer Part Ⅱ： potential roles in management

Predicting treatment responses in advanced prostate cancer （PCa） currently centres on prostate-specific antigen （PSA） kinetics and on being able to visualize measurable changes in imaging modalities. New molecular markers have emerged as potential diagnostic and prognostic indicators; these were summarized in Part I of this review in the Asian Journal ofAndrology. A number of molecular markers are now being used to enhance PCa imaging and staging. However, management options for advanced and hormone-resistant PCa （HRPC） are limited and additional therapeutic options are needed. Molecular markers have been proposed as potential therapeutic targets using gene therapy and immunomodulation. Additionally, markers identified in early PCa and precursor lesions may offer novel targets for chemoprevention and vaccine development. This review summarizes the current advances regarding the roles of these markers in the management of PCa.     

Targeted Anterior Gland Focal Therapy—a Novel Treatment Option for a Better Defined Disease

The goal of focal therapy is to achieve long-term oncological control by eradicating only the clinically significant focus/foci of cancer within the prostate, while preserving erectile function and continence. Anterior prostate cancers may have a PZ or TZ origin and share commonalities in location and biology. While anterior prostate cancers previously constituted a diagnostic blind spot in the prostate and were often not detected or discovered late, with the rapid dissemination of advanced imaging and biopsy techniques, they can now be identified at an earlier, organ-confined stage due to MR imaging and targeted biopsies. Due to their anterior location, they represent a therapeutic target that allows for thorough ablation of the cancer focus/foci with an adequate margin while remaining far from the neurovascular bundles bilaterally. However, the TZ origin cancers are mostly anterior to the distal urethra close to the apex and the striated sphincter. Men having early stage anterior cancers may represent good candidates to achieve a balance between oncological control and functional preservation with focal therapy. Thus, this class of tumor based on location, along with the proposed treatment, represents a novel form of targeted image-guided therapy.     

Fluorodeoxyglucose positron emission tomography studies in the diagnosis and staging of clinically advanced prostate cancer

OBJECTIVE: To determine the value of 18F-fluoro-2-deoxyglucose (FDG) positron-emission tomography (PET) studies in evaluating patients with advanced prostate cancer. PATIENTS AND METHODS: FDG-PET scans were taken in 30 patients with advanced prostate cancer 1 h after an injection with 555 MBq of FDG. Patients were scanned from the base of the skull to the inguinal region (including the pelvis). They were also assessed by computed tomography (CT) of the abdomen and pelvis, and bone scintigraphy, to evaluate them for metastases. RESULTS: Thirteen patients had locally extensive prostate cancer and 17 had metastatic disease. Twenty of the 30 patients were positive for radioisotope uptake in the prostate or extraprostatically. The patients with PET-detected prostate cancer were untreated (seven), treated hormonally while they had rising PSA levels (eight), or treated hormonally with a detectable but stable PSA (five). The remaining 10 patients were negative for FDG uptake in the prostate or any metastatic sites; these 10 patients were receiving hormone therapy, with undetectable PSA levels. CONCLUSION: FDG-PET imaging is not a useful test in evaluating advanced prostate cancer in patients being treated and who have an undetectable PSA level. Staging of advanced prostate cancer may be enhanced by FDG-PET imaging in patients who are untreated, who have had an incomplete response to therapy, or who have a rising PSA level despite treatment.     

Grenzen der Chirurgie bei Karzinomen des oberen Intestinaltraktes

Cancer of the upper gastrointestinal tract is one of the leading causes for cancer related deaths worldwide. While the incidence of esophageal carcinoma is increasing, the incidence of gastric cancer has been continuously decreasing over the past decades. Most patients are often diagnosed with advanced stage disease and the prognosis is still dismal. For many patients surgery is the central part of the therapy; however, improvements in the diagnostic work-up, staging techniques and therapy concepts have led to a more individualized therapeutic approach. Endoscopic treatment of early cancer is well established with high cure rates. In advanced gastric cancer the implementation of multimodal therapies, standardized surgical techniques and optimized perioperative management has led to an improvement in prognosis and outcome. The limitations of surgery in esophagogastric cancer are defined by current scientific results, recent technical developments and patient-specific characteristics. These limitations are continuously changing and require an ongoing review.     

Tissue elasticity imaging for diagnosis of prostate cancer: A preliminary report

BACKGROUND: Elastography is a diagnostic imaging technique that evaluates the hardness of a lesion. It is expected to become a new diagnostic modality for prostate cancer. The aim of this study was to examine the usefulness of elastography in the diagnosis of prostate cancer. METHODS: A total of 29 patients with untreated, histologically proven prostate cancer were examined using an elastographic imaging technique. The patient was scanned in the dorsosacral position and the prostate was manually compressed with a transrectal ultrasonic probe. The echo signals from inside the tissue were measured before and after the tissue compression and an elastogram was generated by spatially differentiation of the displacement distribution. RESULTS: Elastography depicted the cancer lesion as a harder tissue than the surrounding normal prostatic tissue. Elastography successfully detected 93% (27 patients) of the untreated prostate cancer lesions. Detection of cancer lesions using elastography was significantly higher than by digital rectal examination (59%; 17 patients) and transrectal ultrasonography (55%; 16 patients). CONCLUSION: Elastography has great potential as a useful modality for diagnosis of prostate cancer. Differentiation between cancerous and normal tissues can be expected to become more accurate as a result of technical advances in the quantification of tissue hardness.     

Urologic imaging for localized prostate cancer in 2007

Increasing numbers of systematic random biopsies have virtually replaced urologic imaging as a detection and staging tool in prostate cancer. TRUS as the most commonly utilized urologic imaging is now mainly utilized to guide the biopsy needle into the correct anatomical or topographic region of the prostate. But even multiple systematic random biopsies have been shown to overlook a large number of clinically significant carcinoma. This fact has led to a dramatic increase in the number of biopsies taken in the detection of localized prostate cancer. There are some centers where 6, 10, 12, even up to 143 biopsies are taken in one sitting. This increasingly invasive and heterogeneous strategy underlines the need for an improvement in diagnostic imaging. New modalities and innovative techniques are currently being investigated in order to identify prostate cancer more accurately. The purpose of this paper is to review innovative urologic imaging techniques to identify emerging modalities that may be beneficial in the management of prostate cancer. Enhanced transrectal ultrasonography modalities, including ultrasound contrast agents, color and power doppler, elastography and computerized (C)-TRUS with artificial neural network analysis (ANNA) promise benefits in comparison to standard gray-scale ultrasonography to accurately target and diagnose prostate cancer.     

Ad5CMVp53 gene therapy for locally advanced prostate cancer – where do we stand?

Despite the introduction of screening procedures and an increased public awareness of prostate cancer, a substantial number of patients present with locally advanced prostate cancer. Traditional therapies (such as radiation therapy or radical prostatectomy) applied either alone or in combination fail to control local disease in a large number of cases and have no effect on disseminated disease. Recent advances in molecular oncology and genetics have led to such novel therapies as p53 gene therapy, which we are currently evaluating in a clinical protocol in patients with locally advanced (nonmetastatic) prostatic cancer. Ad5CMVp53 (RPR/INGN 201) has previously shown promise in both patients with lung cancer and those with head and neck cancer. The traditional end points used to appraise prostate cancer preclude rapid evaluation of the patient's disease and prevent modification of the therapeutic strategy, and we suggest that the pathologic stage after therapy be evaluated as an intermediate end point.     

Early prostate cancer: is there a need for new treatment options?

Improvements in diagnostic techniques have led to prostate cancer being diagnosed in younger patients and at an earlier stage of disease. The question therefore arises as to what is the best treatment for early prostate cancer. The main issues to be considered are whether the cancer is likely to progress quicker if these patients do not receive early treatment and what the quality of life implications are for patients receiving early treatment. As yet, due to the lack of valid comparisons of treatments, there is no clear "best treatment" for early prostate cancer. A number of clinical trials, comparing current treatments or investigating potential new treatment options for early prostate cancer, are in progress. The results of these should clarify the relative benefits of currently available treatments. This article reviews the latest information on the incidence, prognosis and current treatments for early prostate cancer and discusses the need for new treatments. Potential clinical benefits and cost implications of new treatments for early prostate cancer, such as improved surgical and radiotherapy techniques and adjuvant medical therapy, are also evaluated.     

经尿道电切治疗晚期前列腺癌伴膀胱出口梗阻

目的 总结经尿道前列腺电切治疗晚期前列腺癌伴膀胱出口梗阻的手术经验.方法 本组36例患者,年龄68～89岁,平均76.5岁.术前IPSS评分为(18.3±3.1)分;总PSA分别为(60.1±35.4)ng/ml;最大尿流率为(9.4±2.8)ml/s.穿刺病理确诊为前列腺癌,Gleasn评分为(7.3±1.8)分.Whitmore临床分期C期10例,D期26例.36例患者行经尿道前列腺电切术同时行双睾丸切除术,术后加用(氟他胺250mgtid或者比卡鲁胺50mgqd),行全雄激素阻断.结果 36例均顺利完成手术,无围手术期死亡病例.6例(16.7%)术后出现尿失禁,经保守治疗后治愈.1例术后大出血,二次手术止血后恢复顺利,1例术后4个月再次出现排尿困难,再次行TURP后,患者排尿通畅.随访24～55个月,死亡13例,其中死于前列腺癌10例,平均生存32个月,死于其他疾病3例.术后患者排尿症状明显改善,术后3个月尿流率(17.5±3.5)ml/s,术后IPSS评分(8.1±3.4)分.结论 经尿道前列腺电切是治疗晚期前列腺癌伴膀胱出口梗阻的有效方法,可以快速改善患者的排尿症状,提高尿流率.     

Future prospects for primary hormone therapy in localized and locally advanced prostate cancer

The authors consider current and future prospects for primary hormone therapy in localized and locally advanced prostate cancer by comparing this form of treatment (hormone monotherapy) with neoadjuvant radiation therapy and radical prostatectomy. Neoadjuvant hormone therapy prior to radiation therapy has been proven effective in recent years, and currently the United States is showing a year-by-year increase in the use of androgen blocking agents during the early stage of prostate cancer. A survey of recent research findings, clearly showed that, for patients with localized prostate cancer, there is no significant difference in survival rate between hormone monotherapy and radical prostatectomy. In the future we can expect to see an increase in available treatment options for localized and locally advanced prostate cancer, with the optimal therapy for each individual patient to be selected by the attending physician in discussion with the patient.     

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019

BackgroundInnovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.ObjectiveTo present the results from the APCCC 2019.Design, setting, and participantsSimilar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.Outcome measurements and statistical analysisThe panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.Results and limitationsPanellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.ConclusionsThese voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.Patient summaryThe Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.     

HIFU in urological oncology

The growing interest in high-intensity focused ultrasound (HIFU) technology is mainly due to its many potential applications as a new energy source and as noninvasive therapy. It has been introduced to urological oncology as a transrectal treatment for prostate cancer and as extracorporeal treatment for kidney cancer. Although its application in the kidney is still at the clinical feasibility phase, HIFU technology is currently being used in daily practice in Europe for the treatment of prostate cancer. Reports in the literature describing results of HIFU for prostate cancer are mainly based on monocentric, prospective clinical studies. The latest published results suggest that HIFU treatment is a valuable option for well-differentiated and moderately differentiated tumors, as well as for local recurrence after external beam radiation. Two different devices for transrectal treatment of prostate cancer are available, which are essentially different in technology, application mode, published results, and side effects.HIFU in locally recurrent cancer after surgery, as well as adjuvant HIFU for local debulking in locally advanced or metastatic disease, shows promising first results for reducing local disease-induced morbidity and for delay of progression.     

HIFU in der Uro-Onkologie

The growing interest in high-intensity focused ultrasound (HIFU) technology is mainly due to its many potential applications as a new energy source and as noninvasive therapy. It has been introduced to urological oncology as a transrectal treatment for prostate cancer and as extracorporeal treatment for kidney cancer. Although its application in the kidney is still at the clinical feasibility phase, HIFU technology is currently being used in daily practice in Europe for the treatment of prostate cancer. Reports in the literature describing results of HIFU for prostate cancer are mainly based on monocentric, prospective clinical studies. The latest published results suggest that HIFU treatment is a valuable option for well-differentiated and moderately differentiated tumors, as well as for local recurrence after external beam radiation. Two different devices for transrectal treatment of prostate cancer are available, which are essentially different in technology, application mode, published results, and side effects. HIFU in locally recurrent cancer after surgery, as well as adjuvant HIFU for local debulking in locally advanced or metastatic disease, shows promising first results for reducing local disease-induced morbidity and for delay of progression.     

PSA progression following radical prostatectomy and radiation therapy: new standards in the new Millennium

Prostate-specific antigen (PSA) progression following radical treatments of clinically localized prostate cancer is a common problem facing both the patient and the urologist. Not all patients with relapsing disease have an equal risk of death due to prostate cancer. After surgery, biochemical failure can be defined as persisting detectable levels of PSA after radical prostatectomy or a PSA rise after a period of normalization. On the other hand, definitions of PSA progression after radiation therapy vary and no clear consensus can be found. This review of the recent international literature updates the knowledge about the diagnostic procedures used in relapsing patients. Predictors of progression are precised leading to a better patient selection, based on currently available tables and nomograms. Indeed, identification of high risk patients may allow a more appropriate treatment decision. After radical treatment, the analysis of time to recurrence, PSA doubling time, PSA kinetics combined to modern imaging techniques such as 111In capromab penditide scan may allow a better identification of the recurrence site. Thus, an optimal treatment strategy may be envisaged such as local irradiation, salvage surgery, hormone therapy or combinations for which indications and results are provided. Alternative options such as cryotherapy still need further investigation. At last, the use of artificial neural networks will certainly enhance the selection of patients submitted to radical treatments as well as the selection of relapsing patients to allow a more appropriate adjuvant therapy.     

Will the experience with tamoxifen in breast cancer help define the role of antiandrogens in prostate cancer?

Breast and prostate cancers are the two predominant hormone-responsive tumours. The use of the antioestrogen tamoxifen in the treatment of breast cancer has evolved over the past 30 y from treatment for advanced breast cancer to prevention. Tamoxifen is currently the endocrine treatment of choice for advanced breast cancer and for adjuvant therapy in a broad spectrum of women whose primary tumours have functional oestrogen receptors. It has also been shown to reduce the incidence of breast cancer in high-risk women. Non-steroidal antiandrogen therapy is used in the treatment of prostate cancer, but its role is still being defined. The clinical development of tamoxifen and that of the antiandrogens are reviewed and parallels are uncovered which provide insight into contemporary and future management of hormone-responsive prostate cancer.Prostate Cancer and Prostatic Diseases (2001) 4, 72-80     

Role of robot‐assisted radical prostatectomy in locally advanced prostate cancer

Locally advanced prostate cancer is regarded as a very high‐risk disease with a poor prognosis. Although there is no definitive consensus on the definition of locally advanced prostate cancer, radical prostatectomy for locally advanced prostate cancer as a primary treatment or part of a multimodal therapy has been reported. Robot‐assisted radical prostatectomy is currently carried out even in high‐risk prostate cancer because it provides optimal outcomes. However, limited studies have assessed the role of robot‐assisted radical prostatectomy in patients with locally advanced prostate cancer. Herein, we summarize and review the current knowledge in terms of the definition and surgical indications of locally advanced prostate cancer, and the surgical procedure and perisurgical/oncological outcomes of robot‐assisted radical prostatectomy and extended pelvic lymphadenectomy for locally advanced prostate cancer.     

Treatment for locally advanced prostate cancer: value of surgery

Surgical therapy is not only a therapeutic method but also an important procedure to provide useful information in determining a postoperative treatment strategy. Compared with postoperative cancer staging based on specimens obtained during surgery, more than 30% of cancers were inaccurately staged preoperatively, even when a current advanced diagnostic imaging technique was used. Compared with postoperative histological 30-40% of cancer staging were inaccurately staged based on a preoperative biopsy. These misstaging cases pose a significantly important problem. Approximately 15% and 30% of clinical stage C prostate cancers have been rated as pT2 and pN(+), respectively. Patients with pT3 prostate cancer who underwent radical prostatectomy had 5-year and 10-year overall survival rates of 82% and 67%, respectively, which were comparable to those in patients with pT2 prostate cancer (82% and 67%, respectively). However, patients with prostate cancer rated as pT4 and pN(+) had very poor outcomes with 5-year overall survival rates of 42.4% and 32.6%, respectively. Therefore, even in patients with stage C prostate cancer, surgical therapy should be recommended if no infiltration of adjacent tissue has been noted and the operation is applicable; and an optimal postoperative therapeutic strategy should be selected based on the accurate pathological staging and histological grading using postoperative pathological specimens. Such approaches will prevent unnecessary hormone therapy in patients with pT2 prostate cancer and prevent missing optimal timing for radical cure, as well as allowing appropriate therapy to be selected for patients with pT4 and pN(+) prostate cancer, for whom prognosis may be poor.