ABSTRACT
BACKGROUND: Based on significant progress in recent years, metastatic castration-resistant prostate cancer (mCRPC) patients can be treated better and better. The medications include androgen signaling inhibitors, chemotherapy, 223Ra, and sipuleucel-T. Most patients treated with these agents will still develop primary or secondary resistance against any given drug. The 177Lutetium-PSMA radioligand therapy (177Lu-PSMA-RLT) represents a good reserve option and can be used within compassionate use provisions demonstrating promising efficacy in the majority of patients in Germany. OBJECTIVES: Establishment of status quo of 177Lu-PSMA-RLT in mCRPC in 2020. MATERIALS AND METHODS: Presentation of the therapy landscape in mCRPC and the current evidence on 177Lu-PSMA-RLT after PubMed based literature search. RESULTS: Several larger retrospective studies and the first prospective trials on 177Lu-PSMA-RLT show premature but encouraging evidence on 177Lu-PSMA-RLT to be a promising new option in mCRPC patients. The toxicity profile seems to be favorable. The phase III trial VISION aims to provide evidence for the approval of 177Lu-PSMA-RLT in combination with abiraterone or enzalutamide in patients having been pretreated with enzalutamide or abiraterone and docetaxel. CONCLUSIONS: Despite the promising preliminary results of 177Lu-PSMA-RLT, the efficacy results of VISION need to be awaited prior to using the therapy outside of compassionate use provisions.
Subject(s)
Dipeptides/therapeutic use , Heterocyclic Compounds, 1-Ring/therapeutic use , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Prostatic Neoplasms/radiotherapy , Radiopharmaceuticals/therapeutic use , Dipeptides/administration & dosage , Germany/epidemiology , Heterocyclic Compounds, 1-Ring/administration & dosage , Humans , Ligands , Lutetium , Male , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/pathology , Radiopharmaceuticals/administration & dosage , Treatment OutcomeABSTRACT
The availability of taxane-based chemotherapy and androgen-receptor-targeted agents (ARTAs) have significantly broadened the therapeutic options for patients with metastatic prostate cancer and may also result in longer patient survival. The therapeutic sequence of ARTAs and taxanes may influence outcome and therefore decisions should be made on an individual basis. This article provides guidance for therapeutic decision-making in daily clinical practice by working out criteria that can be used to support individual therapeutic decisions. The focus is on metastatic castration-naive prostate cancer, oligometastatic disease as well as non-metastatic and metastatic castration-resistant prostate cancer.
Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Prostatic Neoplasms, Castration-Resistant/therapy , Androgen Antagonists , Hormone Replacement Therapy , Humans , Male , Molecular Targeted Therapy , Prostate-Specific Antigen/blood , Prostatectomy/methods , Prostatic Neoplasms, Castration-Resistant/blood , Prostatic Neoplasms, Castration-Resistant/pathology , Treatment OutcomeABSTRACT
There is an ongoing change of paradigm in the treatment of metastatic prostate cancer (mPC). Taxan-based chemotherapy demonstrated a prolonged survival of patients in several randomized phase III trials. This is true in the situation of metastatic castration-resistent prostate cancer (mCRPC) as well as in the hormone-naïve stage (metastatic castration-naive PC [mCNPC]). In patients with mCNPC, treatment with docetaxel in combination with androgen deprivation therapy (ADT) prolonged the median total survival time by 15 months in comparison to ADT alone. Comparable results were obtained by the endocrine combination treatment with ADT/abiraterone. With the current data in mind it seems to be useful to discuss the value of early combination therapy with ADT/docetaxel or ADT/abiraterone as well as the impact on further treatment options in the mCRPC setting and to define criteria for treatment decisions in clinical practice.
Subject(s)
Androgen Antagonists/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Docetaxel/therapeutic use , Prostatic Neoplasms, Castration-Resistant/therapy , Androgen Antagonists/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Docetaxel/administration & dosage , Humans , Male , Neoplasm Metastasis , Prostatic Neoplasms, Castration-Resistant/pathology , Randomized Controlled Trials as Topic , Survival Rate , Treatment OutcomeABSTRACT
In March 2017 the 'Advanced Prostate Cancer Consensus Conference' (APCCC) took place in St. Gallen (Switzerland). The APCCC-panelists are internationally well known experts. With the actual data in mind they discussed treatment options for patients with advanced prostate cancer in order to update the international APCCC-recommendations from the previous meeting in 2015. Recently these consensus recommendations have been published in "European Urology".A group of German experts discussed this year APCCC-votes during the meeting and the recommendations that were concluded from the votes from the German perspective. Reasons for an additional German discussion are country-specific variations that may have influenced the APCCC-votes und recommendations. Due to the concept of the APCCC-meeting the wording of the questions could not always be as necessary.One focus of this year consensus discussion was the treatment of metastatic castration-naive prostate cancer (mCNPC). There are new data which may also influence the therapeutic situation of patients with metastatic castration-resistant prostate cancer (mCRPC). Further points of discussion were the impact of new imaging procedures in the clinical setting as well as the treatment of oligometastatic prostate cancer.
Subject(s)
Neoplasm Metastasis/diagnostic imaging , Orchiectomy , Practice Guidelines as Topic , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Radiotherapy, Adjuvant , Urology/standards , Evidence-Based Medicine , Germany , Humans , Lymph Node Excision , Lymphatic Metastasis/diagnostic imaging , Magnetic Resonance Imaging , Male , Switzerland , Treatment OutcomeABSTRACT
BACKGROUND: At the 2016 ASCO annual meeting, new data from two randomized phase III studies concerning taxane-based chemotherapy as a treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) were presented. OBJECTIVES: The focus is on the clinical impact of these data. MATERIALS AND METHODS: A group of German experts in the field of urogenital-oncologic expertise discussed the clinical impact with respect to the current data. RESULTS: The study results support the current clinical data. They confirm the efficacy and safety of cabazitaxel beyond first-line therapy with docetaxel for patients with mCRPC. CONCLUSIONS: Cabazitaxel is an important treatment option after docetaxel progression. With respect to the performance status of a patient, it is adequate to reduce the dosage to 20 mg/m2 cabazitaxel.
Subject(s)
Neoplasms, Second Primary/pathology , Prostatic Neoplasms, Castration-Resistant/drug therapy , Taxoids/therapeutic use , Docetaxel , Humans , Male , Neoplasms, Second Primary/drug therapyABSTRACT
OBJECTIVES: The German S3 guideline on prostate cancer gives recommendations on early detection of prostate cancer. In this study we analyzed the adherence of urologists in private practice from the administrative district of Münster, Germany to this guideline. METHODS: Data were collected through a semistructured survey of 22 urologists based on the COREQ checklist (Consolidated criteria for reporting qualitative research) in four focus groups consisting of five or six urologists in private practice. We developed 23 questions relating to 12 recommendations of the paragraphs of the S3 guidelines dealing with early detection of prostate cancer and prostate biopsy. The recommendations of the guideline are subdivided in nine "strong", one "optional recommendation" and two "statements". The adherence to the guideline was investigated by using frequency and qualitative content analysis (Mayring) based on a mixed methods design. RESULTS: The urologists follow six of the nine "strong recommendations" of the guideline and deviate from three. Reasons for deviations from "strong recommendations" are the following: information about advantages and disadvantages of early detection for prostate cancer, recommendation of a prostate biopsy in case of PSA level ≥4 ng/ml, and indication for repeat biopsy. CONCLUSION: Most of the "strong recommendations" are followed by the interviewed urologists of the administrative district of Münster. Contextually relevant deviations from "strong recommendations" are justified, e. g., the only limited transferability of the PSA threshold of 4 ng/ml derived from population-based studies of asymptomatic men to men presenting in a urologist's office.
Subject(s)
Early Diagnosis , Guideline Adherence , Prostatic Neoplasms/diagnosis , Urology , Biopsy , Checklist , Germany , Humans , Male , Prostate/pathology , Prostatic Neoplasms/pathologyABSTRACT
In March 2015, the first Advanced Prostate Cancer Consensus Conference (APCC) took place in St. Gallen. 41 experts from 17 countries reviewed important areas of controversy in advanced hormone-naive and castration-resistant prostate cancer and gave therapy recommendations. These results have been recently published in "Annals of Oncology". While most of the recommendations from St. Gallen are comprehensible, some of them need to be further discussed. Therefore, we as a German expert panel will critically debate the St. Gallen recommendations. For metastatic hormone-naive prostate cancer, continuous androgen deprivation remains the standard. There is no evidence for superiority of primary maximal androgen deprivation. Patients suitable for chemotherapy, especially in the presence of high tumour burden, should receive androgen deprivation plus taxanes upfront. In metastatic castration resistant prostate cancer, novel hormonal agents like abiraterone or enzalutamid should be the treatment of choice in the majority of patients. Taxanes should be used first-line in patients with unfavourable prognostic markers. Radium-223 is an option in symptomatic patients with bone metastases. There is first evidence that second-line hormonal treatment after first-line failure of a novel endocrine agent has a high failure rate. Cabazitaxel should be part of the treatment sequence in patients with a good performance status. Baseline staging for castration-resistant prostate cancer should include CT-abdomen/-chest and bone scan. Radiographic monitoring should be performed 2 to 3 times a year. Determination of PSA and ALP is to take place every 2 to 4 months.
Subject(s)
Androgen Antagonists/administration & dosage , Practice Guidelines as Topic , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Taxoids/administration & dosage , Urology/standards , Antineoplastic Agents/administration & dosage , Evidence-Based Medicine , Germany , Humans , Male , Neoplasm Metastasis , Treatment OutcomeABSTRACT
INTRODUCTION: The goal of this work was to describe the change of treatment paradigms for metastatic renal cell carcinoma (mRCC) since 2006. PATIENTS AND METHODS: We retrospectively investigated all mRCC patients who were treated with targeted therapy between June 2006 and June 2012 at the University of Münster. RESULTS: In all, 50 of 158 (31.6 %) patients were initially treated with immunotherapy. The most often used second line treatment after immunotherapy was sorafenib (29 patients, 58.0 %). The first line treatment chosen for therapy-naïve patients was sunitinib (68 patients, 63.0 %). There was no statistically significant difference between the two groups (572 vs. 554 days, p = 0.745). A total of 77 patients had synchronous metastasis (48.8 %), 55 of whom underwent cytoreductive nephrectomy. There was a significant survival benefit in favor of surgically treated patients (510 vs. 186 days, p = 0.002). CONCLUSION: After introduction of the new agents treatment paradigms have changed substantially. Immunotherapy is used only rarely. Cytoreductive nephrectomy may continue to be regarded as standard treatment until prospective data are available.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Indoles/therapeutic use , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Molecular Targeted Therapy/methods , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Pyrroles/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/mortality , Combined Modality Therapy , Female , Humans , Immunotherapy , Kidney Neoplasms/mortality , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Nephrectomy , Niacinamide/adverse effects , Niacinamide/therapeutic use , Phenylurea Compounds/adverse effects , Retrospective Studies , Sorafenib , Sunitinib , Survival RateABSTRACT
INTRODUCTION: Laparoscopic management of adrenal benign cysts is the method of choice today. In contrast to the transabdominal laparoscopic approach, retroperitoneoscopy is rarely performed, although it seems to be a comparable method and alternative technique for cyst resection. CASE REPORT: A thin 27-year-old woman in good condition presented with epigastric and left flank pain as well as reflux of gastric acid. A large adrenal cystic lesion was detected on ultrasonography and computed tomography of the abdomen. The question of whether the cyst arose from the upper pole of the left kidney or from the adrenal gland could not be answered. Retroperitoneoscopic excision of the cystic lesion was performed. The histopathological work-up revealed the finding of an adrenal pseudocyst. Symptoms of epigastric and left flank pain as well as reflux of gastric acid resolved after pseudocyst removal. CONCLUSIONS: The retroperitoneoscopic approach for symptomatic adrenal cyst resection represents an effective, cost-reducing and durable treatment.
Subject(s)
Adrenal Gland Diseases/surgery , Cysts/surgery , Laparoscopy , Adrenal Gland Diseases/diagnostic imaging , Adrenal Glands/pathology , Adult , Cysts/diagnostic imaging , Cysts/pathology , Female , Follow-Up Studies , Humans , Laparoscopy/methods , Radiography, Abdominal , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , UltrasonographyABSTRACT
PURPOSE: The Her2/neu oncoprotein, belonging to the erbB-receptor family, is known to contribute to physiological mechanisms of cell proliferation by intrinsic tyrosine-kinase-activity. Overexpression has been shown for several tumors and is known to influence malignant cell proliferation, metastasis and angiogenesis. The clinical use of Her2-targeting agents has emerged in clinical research. In our study, we analyzed Her2/neu expression in urothelial tumors. MATERIALS AND METHODS: Her2/neu expression was evaluated immunohistochemically (IHC) in 127 patients undergoing radical cystectomy (DAKO- Herceptest). Additionally, fluorescent-in-situ-hybridisation (FISH) was carried out in all immunohistochemically "2+" cases (n = 41) to assess gene amplification. After grading the Her2/neu-overall status, Her2/neu expression was correlated with clinicopathological parameters and survival data. RESULTS: An immunohistochemical Her2/neu expression was found in 95 of 127 cases (74.8 %). Of all 41 cases with "2+" staining (32.2 %), 11 cases (26.8 %) showed positive amplification by FISH. Therefore, including the IHC 3+ cases, a Her2/neu overall status of 22 positive (17.3 %) tumors was assessed. Correlation with clinical data showed a relation to lymph node metastasis (P = 0.06), lymph vessel invasion (P = 0.07) and metastasis (P = 0.002). No further associations with other parameters nor with overall survival (P = 0.73) or disease-free survival (P = 0.63) were found. CONCLUSIONS: Her2/neu upregulation is found in invasive bladder cancer with significant differences in protein expression and gene amplification. The association with lymphogenic and distant metastases implicates a late event in carcinogenesis. Moreover, there was no further association with clinicopathological parameters and survival. The possible role of a molecular targeted therapy of advanced bladder cancer with Her2/neu targeting agents should be assessed in further clinical trials.
Subject(s)
Genes, erbB-2/genetics , Receptor, ErbB-2/genetics , Urinary Bladder Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathology , Carcinoma, Transitional Cell/surgery , Cystectomy , Data Interpretation, Statistical , Disease-Free Survival , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Survival Analysis , Time Factors , Up-Regulation , Urinary Bladder/pathology , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/surgeryABSTRACT
Hormone-refractory prostate cancer is diagnosed with increasing incidence and has become a growing challenge for urologists. The improved understanding of the tumor biological mechanisms of the hormone-refractory state has led to innovative therapeutic developments in the field of hormonal and cytotoxic therapies. Recently, two large randomized Phase III trials with docetaxel-based chemotherapy were able to show prolonged survival and a positive influence on pain and quality of life, establishing a new standard of care for these patients. Moreover, bisphosphonates seem to have positive influence on selected patients. In the growing field of molecular targeted therapy, first trials with compounds, such as tyrosine kinase inhibitors, anti-sense oligonucleotides, angiogenesis inhibitors and endothelin receptor antagonists, show promising results in the treatment of patients with hormone-refractory prostate cancer.