Prostatic Neoplasms: Heidenreich A

Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, Zattoni F, Anonymous00089. · Servicio de Urología, Hospital Universitario de Colonia, Colonia, Alemania. · Actas Urol Esp. · Pubmed #19418833 links to  free full text

Abstract: OBJECTIVES: To present a summary of the 2007 version of the European Association of Urology (EAU) guidelines on prostate cancer (PCa). METHODS: A literature review of the new data emerging from 2004 to 2007 was performed by the working panel. The guidelines have been updated, and the level of evidence/grade of recommendation was added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. RESULTS: A full version is available at the EAU Office or at www.uroweb.org. Systemic prostate biopsy under ultrasound guidance is the preferred diagnostic method. Active treatment is mostly recommended for patients with localized disease and a long life expectancy, with radical prostatectomy being shown to be superior to watchful waiting in a prospective randomized trial. Nerve-sparing radical prostatectomy represents the approach of choice in organ-confined disease; neoadjuvant androgen deprivation demonstrates no improvement of outcome variables. Radiation therapy should be performed with at least 72 and 78 Gy in low-risk and intermediate- to high-risk PCa, respectively. Monotherapeutic androgen deprivation is the standard of care in metastatic PCa; intermittent androgen deprivation might be an alternative treatment option for selected patients. Follow-up is largely based on prostate-specific antigen and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy with docetaxel has emerged as the reference treatment for metastatic hormone-refractory PCa. CONCLUSIONS: The knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.

Aus G, Abbou CC, Bolla M, Heidenreich A, Schmid HP, van Poppel H, Wolff J, Zattoni F, Anonymous00098. · No affiliation provided · Eur Urol. · Pubmed #16046052 No free full text.

Abstract: 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.

Berges R, Dreikorn K, Höfner K, Jonas U, Laval KU, Madersbacher S, Michel MC, Muschter R, Oelke M, Pientka L, Tschuschke C, Tunn U, Schalkhäuser K, Göckel-Beining B, Heidenreich A, Rübben H, Schalkhäuser K, Thon W, Thüroff J, Weidner W, Anonymous00196, Anonymous00197, Anonymous00198, Anonymous00199, Anonymous00200. · No affiliation provided · Urologe A. · Pubmed #12715130 No free full text.

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Heidenreich A. · No affiliation provided · Eur Urol. · Pubmed #18640768 No free full text.

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Heidenreich A. · No affiliation provided · Eur Urol. · Pubmed #18524468 No free full text.

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Heidenreich A. · No affiliation provided · Eur Urol. · Pubmed #18243495 No free full text.

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Heidenreich A. · No affiliation provided · Eur Urol. · Pubmed #16631304 No free full text.

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Heidenreich A. · No affiliation provided · Eur Urol. · Pubmed #16517053 No free full text.

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Fitzpatrick JM, Anderson J, Sternberg CN, Fleshner N, Fizazi K, Rébillard X, Dogliotti L, Conti G, Turesson I, James N, Heidenreich A, Solsona E, Guillem V, Herchenhorn D, Moul J, van Moorselaar J, Coetzee LJ, Wilson A, Bamias A, De Wit R, Chrisofos M. · Mater Misericordiae Hospital and University College Dublin, Dublin, Ireland. · Crit Rev Oncol Hematol. · Pubmed #18723368 No free full text.

Abstract: A multidisciplinary panel of 20 international experts, including urologists, radiation oncologists, and medical oncologists, convened during the Advanced Prostate Cancer Multidisciplinary Team meeting in Rome, Italy, in January 2007, to discuss the multidisciplinary team approach and current patterns of care for patients with hormone-refractory prostate cancer (HRPC). During the meeting, the experts discussed several definitions currently used in prostate cancer management, including those for senior adult patients. In addition, the panel reviewed a series of patient case studies in order to provide feedback on current treatment practices and to identify possible strategies for best practice. It was stressed that treatment decisions for senior adult patients should not be based solely on patient age. Additionally, although historically treatment decisions for advanced prostate cancer have focused on palliative care, given the survival benefit associated with docetaxel-based chemotherapy across patient subgroups, more men are likely to be offered chemotherapy for advanced-stage disease in the future.

Heidenreich A, Pfister D, Ohlmann CH, Engelmann UH. · Bereich Urologische Onkologie,Klinik und Poliklinik für Urologie, Universität zu Köln, Köln, Germany. · Urologe A. · Pubmed #18273599 No free full text.

Abstract: Androgen deprivation (ADT) by medical or surgical castration represents the standard therapeutic approach for managing prostate cancer (PCA) with systemic or locoregional metastases. Although ADT has been successfully used for more than 60 years, there are still major controversies with regard to the initiation (early versus delayed), type (complete versus monotherapy), and duration (continuous versus intermittent) of treatment. It is the purpose of this review to critically present the results of the various ADT options.Bilateral orchiectomy and subcutaneous application of luteinising hormone-releasing hormone (LHRH) analogues represent the guideline-recommended standard treatment for metastatic PCA, whereas estrogens are no longer recommended because of significant cardiovascular side effects despite comparable therapeutic efficacy. Antiandrogen monotherapy with bicalutamide is comparable to LHRH analogues in men with minimal tumour burden. However, survival rates are inferior in patients with extensive metastatic disease, in whom medical or surgical castration should be favoured. Complete ADT results in a median survival benefit of about 5% in men with low metastatic tumour burden, and it cannot be recommended for routine use.Early ADT is associated with a significant advantage in terms of symptom-free survival and prevention of metastasis-associated complications, but it does not result in a prolonged progression-free and overall survival when compared with delayed ADT. Despite encouraging results, intermittent ADT remains an experimental therapeutic approach that should be considered on an individual basis in carefully selected patients. Adjuvant ADT is still discussed controversially for men after radical prostatectomy, whereas it has become the standard approach in patients who undergo external beam radiation for locally advanced PCA.

Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, Zattoni F, Anonymous00006. · Department of Urology, University Hospital Cologne, Cologne, Germany. · Eur Urol. · Pubmed #17920184 No free full text.

Abstract: OBJECTIVES: To present a summary of the 2007 version of the European Association of Urology (EAU) guidelines on prostate cancer (PCa). METHODS: A literature review of the new data emerging from 2004 to 2007 was performed by the working panel. The guidelines have been updated, and the level of evidence/grade of recommendation was added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. RESULTS: A full version is available at the EAU Office or at www.uroweb.org. Systemic prostate biopsy under ultrasound guidance is the preferred diagnostic method. Active treatment is mostly recommended for patients with localized disease and a long life expectancy, with radical prostatectomy being shown to be superior to watchful waiting in a prospective randomized trial. Nerve-sparing radical prostatectomy represents the approach of choice in organ-confined disease; neoadjuvant androgen deprivation demonstrates no improvement of outcome variables. Radiation therapy should be performed with at least 72 and 78 Gy in low-risk and intermediate- to high-risk PCa, respectively. Monotherapeutic androgen deprivation is the standard of care in metastatic PCa; intermittent androgen deprivation might be an alternative treatment option for selected patients. Follow-up is largely based on prostate-specific antigen and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy with docetaxel has emerged as the reference treatment for metastatic hormone-refractory PCa. CONCLUSIONS: The knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.

Heidenreich A, Ohlmann CH, Polyakov S. · Division of Oncological Urology, Department of Urology, University of Cologne, Cologne, Germany. · Eur Urol. · Pubmed #17448592 No free full text.

Abstract: OBJECTIVES: The rationale for locoregional staging lymphadenectomy in prostate cancer (pCA) lies in the accurate diagnosis of occult micrometastases to stratify patients who might benefit from adjuvant therapeutic measures. In pCA, the issues of the necessity and the therapeutic advantage of pelvic lymphadenectomy (PLND]) in patients with low-, intermediate-, and high-risk disease are still discussed controversially. The aim of this review manuscript is to critically evaluate the current status on PLND in pCA. METHODS: A review of the literature was performed concerning radical prostatectomy and PLND with respect to anatomical extent, oncological outcome, and associated complications. RESULTS: The anatomical lymphatic drainage of the prostate includes the obturator fossa, and the external and internal iliac arteries; therefore, at least these areas should be included in PLND. According to the current clinical studies, extended PLND (ePLND) significantly increases the yield of both total lymph nodes and lymph node metastases independent of the risk classification of pCA. Lymph node metastases will be detected in about 5-6%, 20-25%, and 30-40% of low-, intermediate-, and high-risk pCA, respectively. Exclusively 25% of all positive lymph nodes are located in the area around the internal iliac artery. With regard to progression-free and cancer-specific survival, retrospective analysis of the SEER data and additional case-control studies indicate a direct positive relationship between the number of removed lymph nodes and long-term oncological outcome in patients with limited lymph node involvement or negative lymph nodes. In these patients, cancer-specific survival is improved by about 15-20%. On the basis of results of large case-control studies, complication rates of ePLND are not significantly increased. CONCLUSIONS: On the basis of current data, the following conclusions can be drawn: (1) If performed, PLND has to be done in the extended, anatomically adequate variant. (2) The frequency of lymph node metastases in low-risk pCA is low, and the issue of PLND has to be discussed with the patient. (3) If radical prostatectomy is performed in intermediate- and high-risk pCA, an ePLND should be option of choice. For the future, ongoing prospective trials have to demonstrate a benefit in terms of biochemical-free and cancer-specific survival.

Kurth AA, Heidenreich A, Diel I. · Orthopädische Universitätsklinik, Stiftung Friedrichsheim, Marienburgstrasse 2, 60528 Frankfurt/M. · Orthopade. · Pubmed #17252255 No free full text.

Abstract: Since bone metastases occur as a result of hematogenous spreading of tumor cells, therapy with curative intent is no longer feasible and palliative options for treating and preventing skeletal events are essential. Today, bisphosphonates are established in the systemic treatment of bone metastases. This report provides an overview of molecular mechanisms of action and clinical data of bisphosphonates in patients with skeletal metastases of breast and prostate cancer as the most common solid tumors which spread to the bone.

Heidenreich A. · Sektion für Urologische Onkologie, Klinik und Poliklinik für Urologie, Universität zu Köln. · Urologe A. · Pubmed #16311709 No free full text.

Abstract: PSA-progression following primary ADT defines an androgen-refractory but still hormone sensitive PCA which might respond to secondary hormonal manipulations. Secondary hormonal manipulations will result in a PSA decline >50% in about 60-80% of the patients with a mean duration of 7-17 months depending on the type of treatment. PSA-progression following secondary endocrine treatment defines hormone-refractory prostate cancer (HRPCA) which might be treated by systemic chemotherapy. Based on the results of 2 prospective, randomized clinical phase-III trials comparing docetaxel and mitoxantrone, docetaxel results in a statistically significant survival benefit of 2.5 months, a significantly higher PSA- and pain response and represents the treatment of choice in the management of HRPCA. Bisphosphonates such as zoledronate represent another cornerstone in the management of PSA-progressive PCA demonstrating a significant benefit with regard to the prevention of skeletal related events. Furthermore, bisphosphonates might be indicated in the treatment of symptomatic bone pain. The current article critically reflects the various therapeutic options in the management of PSA progression following primary androgen deprivation for advanced prostate cancer.

Heidenreich A, Ohlmann CH. · Sektion für Urologische Onkologie, Klinik und Poliklinik für Urologie, Universität, Köln. · Urologe A. · Pubmed #16237541 No free full text.

Abstract: Surgical or medical androgen deprivation therapy in its multiple variants represents the standard therapeutic approach in the management of metastatic prostate cancer resulting in a primary response rate of about 90%. However, about 90% of the men treated will develop PSA progression within 3-4 years resulting in androgen-independent and later on hormone-refractory prostate cancer. Management of AIPCA and HRPCA still represents a therapeutic challenge despite the development of new and effective treatment options. PSA progression following primary ADT defines an androgen-refractory but still hormone-sensitive PCA which might respond to secondary hormonal manipulations such as antiandrogen withdrawal, addition of nonsteroidal antiandrogens, and administration of estrogens, ketoconazole and hydrocortisone, and somatostatin analogues. Secondary hormonal manipulations will result in a PSA decline >50% in about 60-80% of the patients with a mean duration of 7-17 months depending on the type of treatment. PSA progression following secondary endocrine treatment defines hormone-refractory prostate cancer (HRPCA) which might be treated by systemic chemotherapy. Based on the results of two prospective, randomized clinical phase III trials comparing docetaxel and mitoxantrone, docetaxel results in a statistically significant survival benefit of 2.5 months, a significantly higher PSA and pain response, and represents the treatment of choice in the management of HRPCA.Bisphosphonates such as zoledronate represent another cornerstone in the management of PSA-progressive PCA demonstrating a significant benefit with regard to the prevention of skeletal-related events. Furthermore, bisphosphonates might be indicated in the treatment of symptomatic bone pain as has been demonstrated for ibandronate and zoledronate. The current article critically reflects on the various therapeutic options in the management of PSA progression following primary androgen deprivation for advanced prostate cancer. The development, rationale, and results of systemic chemotherapy are discussed critically and a therapeutic algorithm is demonstrated.

Heidenreich A. · Department of Urology, Philipp University Marburg, Marburg, Germany. · Oncology. · Pubmed #12949427 No free full text.

Abstract: Prostate cancer (PCA) frequently metastasizes to the bones, and skeletal metastases represent the most common cause of morbidity in advanced PCA. Besides the development of skeletal events due to metastases, patients with PCA are at higher risk for benign osseous complications, such as osteoporosis and fractures. Bisphosphonates (BPs) have emerged as an integral part of the management of skeletal disease related to PCA. Currently available data support their routine use to prevent androgen-deprivation-induced osteoporosis and its secondary complications. Dosing at 3-month intervals is appropriate; further studies will have to demonstrate the efficacy of annual dosing. In men with already established bone metastases, BPs might be helpful in preventing skeletal-related events in patients who do not respond to alternative therapies and are at high risk for bone fractures or spinal cord compression. In patients with hormone-refractory prostate cancer, BPs might be administered for analgesic purposes. Prospective randomized trials will have to explore the clinical role of BPs in the prevention of bone metastases following local therapy with curative intent in men at high risk for PCA recurrences.

Heidenreich A, von Knobloch R, Hofmann R. · Department of Urology, Phillips University Marburg, Germany. · Eur Urol. · Pubmed #11223670 No free full text.

Abstract: Adenocarcinoma of the prostate is the most prevalent neoplastic disease in men and continues to be a major cause of morbidity and mortality. Death from prostate cancer is associated with objective and biochemical progression following hormonal manipulations often described as hormone refractory prostate cancer (HRPCA). Therapy for HRPCA is primarily palliative and therapeutic efficacy has to be balanced against potential treatment-related side effects. Therapeutic efficacy may be assessed by evaluating the percentage of patients obtaining a PSA decline of > 50%, evaluating the response of bidimensionally measurable disease or by improvements in quality of life assessments. The most effective cytotoxic therapies at the present time seem to be combinations of estramustine phosphate with taxanes and etoposide. Regimes employing ketoconazole with estramustine, vinblastine or bisphosphonates seem to be worthy of further evaluation. Mitoxantrone has an impressive palliative effect in patients, particularly when combined with hydrocortisone. Oral chemotherapeutic regimens with a combination of estramustine phosphate, cyclophosphamide and prednisone appear to offer a less toxic alternative. For the future we need prospective randomized clinical phase-III studies, prognosticators identifying patients as being at high or low risk who might benefit from different therapeutic approaches and generally binding eligibility and response guidelines in order to be able to compare trials of different therapeutic approaches.

Heidenreich A, von Knobloch R, Hofmann R. · Klinik und Poliklinik für Urologie, Philipps-Universität Marburg. · Urologe A. · Pubmed #10591808 No free full text.

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Heidenreich A. · Department of Urology, University of Cologne, Germany. · Recent Results Cancer Res. · Pubmed #17432558 No free full text.

Abstract: Prostate cancer is often a complex disease and one in which many aspects of the disease and the affected patient must be taken into consideration before decisions about diagnostic work-up, treatments, follow-up, etc. can be made. The current chapter reflects the current recommendations of the European Prostate Cancer Guideline Group made on the basis of criteria of evidence-based medicine after extensive review of the literature available up to December 2005.

Ohlmann CH, Kohlmorgen S, Sahi D, Engelmann U, Heidenreich A. · Klinik und Poliklinik für Urologie, Klinikum der Universität zu Köln, 50937 Köln. · Urologe A. · Pubmed #17563866 No free full text.

Abstract: We report on the lethal course of a patient receiving low-dose, weekly docetaxel who developed acute liver failure accompanied by a Stevens-Johnson syndrome. After receiving the fifth application of his chemotherapy, the patient was admitted to hospital because of neutropenia and severe erythema. The course worsened towards an acute liver failure and an erythema multiforme major. Despite an interdisciplinary approach, the further course could not be influenced and the patient died 6 weeks after admission due the toxicity of docetaxel. This case report underlines the spectrum of toxicity of docetaxel even in the low-dose weekly schedule.

Heidenreich A, Sommer F, Ohlmann CH, Schrader AJ, Olbert P, Goecke J, Engelmann UH. · Department of Urology, University of Cologne, Germany. · Cancer. · Pubmed #15329902 links to  free full text

Abstract: BACKGROUND: Liposomal encapsulation of doxorubicin has been shown to reduce nonspecific delivery of this agent to normal tissue and to increase specific delivery to malignant cells. On the basis of doxorubicin's demonstrated clinical efficacy against hormone-refractory prostate carcinoma (HRPCA), the authors conducted a prospective, randomized Phase II clinical trial to evaluate the feasibility, toxicity, and therapeutic efficacy associated with the pegylated form of this agent. METHODS: Forty-eight patients with symptomatic HRPCA were randomized to receive pegylated liposomal doxorubicin at either 25 mg/m2 every 2 weeks for 12 cycles (Group A) or 50 mg/m2 every 4 weeks for 6 cycles (Group B). Thirty-eight of these 48 patients (79%) presented with severe pain (corresponding to a pain score of 7.5 on a visual analog scale [VAS] ranging from 0 to 10) due to osseous metastases. Therapeutic efficacy was assessed by serial evaluation of serum prostate-specific antigen (PSA) concentrations and by serial measurement of pain levels (using a VAS ranging from 0 to 10). Toxicity data were obtained using the National Cancer Institute of Canada/Cancer and Leukemia Group B criteria and the 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. RESULTS: The median patient age was 68.9 years (range, 58-79 years), and the mean follow-up duration was 42 months. The mean pretreatment PSA level was 660.4 ng/mL (mean, 8-6340 ng/mL); an objective decrease in PSA levels (i.e., a decrease of > 50%) was observed in 8 of 31 patients (25.8%) in Group B, whereas no other patient in either group experienced such a decrease. The mean time to disease progression was 6.5 months, and the mean survival duration was 13.4 months. Patients in Group B had a significantly higher rate of response with respect to pain (52.6% vs. 28.6%; P = 0.04), and the mean 1-year survival rate also was significantly higher in Group B (42% vs. 15%; P = 0.02). Severe side effects were observed, with 24 patients (50%) experiencing World Health Organization Grade 3/4 toxicity. Toxicity types differed significantly between Group A and Group B; palmar-plantar erythrodysesthesia developed in 60% of patients in the former group (P < 0.0005), whereas tachycardia was more common in the latter group (39% of patients; P < 0.0005). No dose-limiting cardiotoxicities or hematotoxicities were documented. CONCLUSIONS: Pegylated liposomal doxorubicin yielded a noteworthy objective palliative response rate and a mean survival of 13 months for patients with symptomatic HRPCA. The dosage tested in the current study should be used in future Phase II and Phase III trials of pegylated liposomal doxorubicin-containing combination regimens for patients with HRPCA.

von Knobloch R, Weber J, Varga Z, Feiber H, Heidenreich A, Hofmann R. · Department of Urology, Philipps-University Marburg Medical School, Baldingerstrasse, D-35043, Marburg, Germany. · Eur Urol. · Pubmed #12074792 No free full text.

Abstract: INTRODUCTION: Transrectal multi-core biopsies of the prostate can cause substantial discomfort with the need for high dose systemic analgesics. In a prospective randomised trial we investigated the efficacy of fine-needle administered local anaesthesia for bilateral prostatic nerve block prior to transrectal ultrasound (TRUS) guided prostate biopsy.MATERIALS AND METHODS: One hundred and eight men suspected of having cancer of the prostate were randomised to receive TRUS-guided bilateral prostate nerve block prior to biopsy or not, when having no history of previous prostate biopsies (groups I and II, n=68). In group III (n=40) all patients with history of previous biopsies exclusively received local anaesthesia injection. Patients routinely underwent a 10-core biopsy regimen. For repeat biopsy 12 cores were taken. The consented patients documented pain on a visual analogue pain score.RESULTS: In the randomised groups I and II average pain score was 1.85 with versus 3.29 without periprostatic nerve block (p<0.0001). In group III the difference in pain stated for the present biopsy with local anaesthesia nerve block in comparison to the pain experienced with the previous biopsy solely under transrectal lidocaine gel was even higher (1.71 versus 4.59; p<0.0001). Pain relief was independent of the number of biopsy cores sampled. Overall cancer detection rate was 46% (50/108).CONCLUSION: Bilateral local anaesthesia nerve block prior to multi-core TRUS-guided prostate biopsy significantly reduces pain independent of the number of cores taken.

Heidenreich A, Hofmann R, Engelmann UH. · Departments of Urology, Philipps-University, Marburg and University of Cologne, Cologne, Germany. · J Urol. · Pubmed #11125382 No free full text.

Abstract: PURPOSE: Hormone refractory prostate cancer is dominated by osseous metastases leading to bone pain and pathological fractures. We assessed the clinical efficacy of bisphosphonate in the management of symptomatic skeletal metastases due to prostate cancer. MATERIALS AND METHODS: A total of 85 patients with painful osseous metastases due to hormone refractory prostate cancer were treated with clodronate in an open prospective nonrandomized clinical study. Clodronate was started as an intravenous phase for 8 days at a dose of 300 mg. daily followed by an oral maintenance phase of 1,600 mg. daily. The primary study end point was decreased pain without an increase in analgesic medication for at least 2 consecutive measurements. Secondary end points were decreased analgesics, an improved Karnofsky index and mobility as well as the duration of bisphosphonate action. Decreased pain was documented by a 10-point visual analog scale and consumption of analgesics was documented in a diary. RESULTS: A palliative response with a significant decrease in mean pain score from 7.9 (range 6 to 10) to 2.5 (range 0 to 4) (p <0.001) was achieved in 64 of the 85 patients (75%), 19 (22%) were completely pain-free without further need of analgesics and 45 significantly decreased the daily consumption of analgesics. The mean duration of bisphosphonate action was 9 weeks (range 4 to 22) and mean survival was 12 weeks (range 6 to 22). Improvement in bone pain was paralleled by an improvement in the mean Karnofsky index of 45% (range 30% to 60%) to 70% (range 50% to 80%) at the end of the treatment period. CONCLUSIONS: Bisphosphonate treatment of painful osseous metastases due to hormone refractory prostate cancer results in a significant pain decrease and a significant decrease in the daily consumption of analgesics in 75% of patients. Each characteristic is paralleled by an increase in the Karnofsky index, mainly due to better mobility. Bisphosphonate should have a definite role in the palliative management of symptomatic hormone refractory prostate cancer.

Heidenreich A, Semrau R, Thüer D, Pfister D. · Bereich Uro-Onkologie,Klinik und Poliklinik für Urologie, Uniklinik, Kerpener Strasse 62, 50924, Köln, Deutschland. · Urologe A. · Pubmed #18806991 No free full text.

Abstract: External beam radiation and low- and high-dose interstitial brachytherapy represent therapeutic alternatives to radical prostatectomy for organ-confined and locally advanced prostate cancer. Local recurrences are described in 5-35% of the patients depending on the individual risk profile, and most recurrences are detected due to asymptomatic PSA rise only. According to the most recent data, recurrences are defined by a PSA increase >2 ng/ml above the post-radiation nadir. Radical salvage prostatectomy represents a secondary local treatment with curative intent in patients with organ-confined recurrences. Preoperative risk factors predicting organ-confined disease are initial LDR brachytherapy, preoperative Gleason biopsy score < or =6, < or =50% biopsy cores involved with cancer, and a PSA doubling time >12 months. Metastatic disease should be ruled out preoperatively by skeletal scintigraphy, computed tomography, or magnetic resonance imaging of the abdomen and the small pelvis, and/or choline PET/CT. Functionality of the lower urinary tract is evaluated by urethrocystoscopy and urodynamics. The most appropriate candidates for radical salvage prostatectomy are patients with organ-confined disease or those with symptomatic local recurrences. In experienced hands, morbidity is low with a continence rate of 83-96% depending on the type of previous radiation therapy. Long-term oncological control can be achieved in more than 80% of the patients.

Ohlmann CH, Markert E, Gerharz M, Pfister D, Dienes HP, Engelmann U, Heidenreich A. · Klinik für Urologie und Kinderurologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland. · Urologe A. · Pubmed #18679646 No free full text.

Abstract: Targeted therapies present an interesting treatment option in prostate cancer. The aim of our study was to analyze the expression profile of several molecular markers that are candidates for targeted therapy in patients with progressive androgen-independent prostate cancer (AIPC). Based on the expression profile, the efficacy of a combination therapy with a signal transduction inhibitor (STI) and docetaxel was evaluated.Tumor tissue obtained from biopsy of the prostate or lymph node and visceral metastasis was analyzed for the immunohistochemical expression of epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor beta (PDGFRbeta), Her-2/neu, c-KIT, and vascular endothelial growth factor (VEGF). Patients with positive staining of one or more markers were treated with the corresponding STI and docetaxel.Fifty-one patients were included in the protocol, of whom 43 (84.3%) presented with progressive AIPC after first-line chemotherapy. Forty-six of these 51 patients (90.2%) showed expression of one or more of the analyzed markers. Expression of EGFR was found in 61.2%, PDGFRbeta in 57.1%, Her-2/neu in 16.3%, c-KIT in 25.0%, and VEGF in 74.5%. After request for cost coverage, 8/51 patients received the combination therapy and were evaluated for response. Four of the eight patients (50%) showed a decline in prostate-specific antigen of > or =50%, and median survival time was 13.5 months at a median follow-up of 23.6 (11-35) months.The results show that expression of molecular targets is found in about 90% of patients with AIPC. Based on the expression profile, an individual treatment strategy can be applied to each patient. Further clinical studies should determine the clinical efficacy of molecular targeted therapy in patients with AIPC.