D. Pfister

Early Salvage Radiotherapy Following Radical Prostatectomy

CONTEXT Depending on the pathologic tumour stage, up to 60% of prostate cancer patients who undergo radical prostatectomy will develop biochemical relapse and require further local treatment. OBJECTIVES We reviewed the results of early salvage radiation therapy (RT), defined as prostate-specific antigen (PSA) values prior to RT ≤ 0.5 ng/ml in the setting of lymph node-negative disease. EVIDENCE ACQUISITION Ten retrospective studies, including one multicentre analysis, were used for this analysis. Among them, we received previously unpublished patient characteristics and updated outcome data from five retrospective single-centre trials to perform a subgroup analysis for early salvage RT. EVIDENCE SYNTHESIS Patients treated with early salvage RT have a significantly improved biochemical recurrence-free survival (BRFS) rate compared with those receiving salvage RT initiated after PSA values are >0.5 ng/ml. Similarly, within the cohort of patients with pre-RT PSA values <0.5 ng/ml, improved BRFS rates were noted among those with lower rather higher pre-RT PSA levels. It is possible that higher RT dose levels and the use of adjunctive androgen-deprivation therapy improve biochemical control outcomes in the salvage setting. CONCLUSIONS Based on a literature review, improved 5-yr BRFS rates are observed for patients who receive early salvage RT compared with patients treated with salvage RT with a pre-RT PSA value >0.5 ng/ml. Whether the routine application of early salvage RT in patients with initially undetectable PSA levels will be associated with demonstrable clinical benefit awaits the results of ongoing prospective trials.

Cytoreductive Radical Prostatectomy in Patients with Prostate Cancer and Low Volume Skeletal Metastases: Results of a Feasibility and Case-Control Study

PURPOSE Androgen deprivation represents the standard treatment for prostate cancer with osseous metastases. We explored the role of cytoreductive radical prostatectomy in prostate cancer with low volume skeletal metastases in terms of a feasibility study. MATERIALS AND METHODS A total of 23 patients with biopsy proven prostate cancer, minimal osseous metastases (3 or fewer hot spots on bone scan), absence of visceral or extensive lymph node metastases and prostate specific antigen decrease to less than 1.0 ng/ml after neoadjuvant androgen deprivation therapy were included in the feasibility study (group 1). A total of 38 men with metastatic prostate cancer who were treated with androgen deprivation therapy without local therapy served as the control group (group 2). Surgery related complications, time to castration resistance, and symptom-free, cancer specific and overall survival were analyzed using descriptive statistical analysis. RESULTS Mean patient age was 61 (range 42 to 69) and 64 (range 47 to 83) years in groups 1 and 2, respectively, with similar patient characteristics in terms of initial prostate specific antigen, biopsy Gleason score, clinical stage and extent of metastatic disease. Median followup was 34.5 months (range 7 to 75) and 47 months (range 28 to 96) in groups 1 and 2, respectively. Median time to castration resistant prostate cancer was 40 months (range 9 to 65) and 29 months (range 16 to 59) in groups 1 and 2, respectively (p=0.04). Patients in group 1 experienced significantly better clinical progression-free survival (38.6 vs 26.5 months, p=0.032) and cancer specific survival rates (95.6% vs 84.2%, p=0.043), whereas overall survival was similar. Of the men in groups 1 and 2, 20% and 29%, respectively, underwent palliative surgical procedures for locally progressing prostate cancer. CONCLUSIONS Cytoreductive radical prostatectomy is feasible in well selected men with metastatic prostate cancer who respond well to neoadjuvant androgen deprivation therapy. These men have a long life expectancy, and cytoreductive radical prostatectomy reduces the risk of locally recurrent prostate cancer and local complications. Cytoreductive radical prostatectomy might be a treatment option in the multimodality management of prostate cancer with minimal osseous metastases.

Cabazitaxel Plus Prednisone for Metastatic Castration-resistant Prostate Cancer Progressing After Docetaxel: Results from the German Compassionate-use Programme

BACKGROUND Cabazitaxel (Cbz) is an approved second-line treatment in metastatic castration-resistant prostate cancer (mCRPC) following docetaxel therapy with a significant survival benefit compared with mitoxantrone. However, grade 3/4 toxicities were reported in 82% of patients. OBJECTIVE To report on the safety results of mCRPC patients treated within a compassionate-use programme in Germany. DESIGN, SETTING, AND PARTICIPANTS A total of 111 patients with a mean age of 67.9 yr (range: 49-81 yr) and progressive mCRPC were included. Patients had received a mean number of 12.7 ± 10.8 cycles (range: 6-69 cycles) of docetaxel with a mean cumulative dose of 970.9 mg/m(2); mean time from last docetaxel application to progression was 6.95 mo (range: 2-54 mo). Of the patients, 31.5% progressed by prostate-specific antigen (PSA) increase only; the remainder had a combination of PSA increase and clinical progression. INTERVENTION Cbz at a dosage of 25mg/m(2) intravenously every 3 wk combined with 5mg of oral prednisone twice a day. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Treatment-associated toxicity was the primary study end point; progression-free and overall survival were secondary end points. A descriptive statistical analysis was performed. RESULTS AND LIMITATIONS Patients received a mean number of 6.5 ± 2.2 cycles of Cbz and a mean cumulative dose of 160.3 ± 51.5mg/m(2). Grade 3 and 4 treatment-emergent adverse events were recorded in 34 patients (30.6%) and 18 patients (16.2%), respectively. Grade 3/4 anaemia, neutropenia, and thrombocytopenia were reported in 4.5%, 7.2%, and 0.9% of the patients, respectively. Neutropenic fever was reported in 1.8% of the patients. Grade 3/4 gastrointestinal toxicity was identified in 4.5% of the patients. Three patients died because of Cbz-related toxicity. Granulocyte colony-stimulating growth factors were used in 17.1% of patients. The limitations are due to the nonrandomised nature of the trial. CONCLUSIONS Treatment with Cbz is tolerable and is associated with a low incidence of serious adverse events in a real-world patient population with CRPC. The outcome of serious adverse events can be minimised with proactive treatment management and conscientious monitoring.

Residual Tumor Size and IGCCCG Risk Classification Predict Additional Vascular Procedures in Patients with Germ Cell Tumors and Residual Tumor Resection: A Multicenter Analysis of the German Testicular Cancer Study Group

BACKGROUND Residual tumor resection (RTR) after chemotherapy in patients with advanced germ cell tumors (GCT) is an important part of the multimodal treatment. To provide a complete resection of residual tumor, additional surgical procedures are sometimes necessary. In particular, additional vascular interventions are high-risk procedures that require multidisciplinary planning and adequate resources to optimize outcome. OBJECTIVES The aim was to identify parameters that predict additional vascular procedures during RTR in GCT patients. DESIGN, SETTING, AND PARTICIPANTS A retrospective analysis was performed in 402 GCT patients who underwent 414 RTRs in 9 German Testicular Cancer Study Group (GTCSG) centers. Overall, 339 of 414 RTRs were evaluable with complete perioperative data sets. MEASUREMENTS The RTR database was queried for additional vascular procedures (inferior vena cava [IVC] interventions, aortic prosthesis) and correlated to International Germ Cell Cancer Collaborative Group (IGCCCG) classification and residual tumor volume. RESULTS AND LIMITATIONS In 40 RTRs, major vascular procedures (23 IVC resections with or without prosthesis, 11 partial IVC resections, and 6 aortic prostheses) were performed. In univariate analysis, the necessity of IVC intervention was significantly correlated with IGCCCG (14.1% intermediate/poor vs 4.8% good; p=0.0047) and residual tumor size (3.7% size < 5 cm vs 17.9% size ≥ 5 cm; p < 0.0001). In multivariate analysis, IVC intervention was significantly associated with residual tumor size ≥ 5 cm (odds ratio [OR]: 4.61; p=0.0007). In a predictive model combining residual tumor size and IGCCCG classification, every fifth patient (20.4%) with a residual tumor size ≥ 5 cm and intermediate or poor prognosis needed an IVC intervention during RTR. The need for an aortic prosthesis showed no correlation to either IGCCCG (p=0.1811) or tumor size (p=0.0651). CONCLUSIONS The necessity for IVC intervention during RTR is correlated to residual tumor size and initial IGCCCG classification. Patients with high-volume residual tumors and intermediate or poor risk features must initially be identified as high-risk patients for vascular procedures and therefore should be referred to specialized surgical centers with the ad hoc possibility of vascular interventions.

Percentage of positive biopsies predicts lymph node involvement in men with low-risk prostate cancer undergoing radical prostatectomy and extended pelvic lymphadenectomy

Study Type – Diagnostic (exploratory cohort)
Level of Evidence 2b

Proteomic tissue profiling for the improvement of grading of noninvasive papillary urothelial neoplasia.

OBJECTIVES In 2004, a novel grading system for papillary non-invasive bladder cancer was introduced; low grade (LG) and high grade (HG) in lieu of the former G1, G2, G3. This change allowed for increased reproducibility as well as diminished interobserver variability in histopathological grading among individual pathologists. Matrix Assisted Laser Desorption/Ionization Time of Flight Imaging Mass Spectrometry (MALDI TOF IMS) was evaluated as an automatic and objective tool to assist grading of urothelial neoplasms and to facilitate accuracy. DESIGN AND METHODS To separate G1 (LG, n=27) and G3 (HG, n=21) papillary tumors MALDI TOF IMS was performed using an appropriate algorithm. Thereafter, the automatic assignment of a separate G2 (n=31) group was completed. RESULTS G1 (LG) and G3 (HG) tumors were separated with an overall cross validation of 97.18%. G2 tumors indicated a true positive rate of 78.3% for LG and 87.5% for HG, respectively. CONCLUSIONS MALDI TOF IMS is a powerful support tool to ascertain pathological diagnosis/grading.

Castration-resistant Prostate Cancer: Where We Stand in 2013 and What Urologists Should Know

Patients with metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis, and those patients with metastases are expected to survive 19 mo [1]. As patients’ disease progresses, quality of life deteriorates, and until recently, few treatment options were available. Several new therapies have shown an improvement in overall survival for patients with mCRPC who have already received chemotherapy with docetaxel (Fig. 1) [2–6]. The impact of these new data on daily clinical practice, treatment sequencing, and best care for individual patients is not yet fully understood. The purpose of this editorial is to highlight the most recent, clinically relevant results of the new therapeutic options that have been either newly published or presented at the 2013 American Society of Clinical Oncology Genitourinary Cancers Symposium (February 14–16, 2013; Orlando, FL, USA) or the 28th Annual European Association of Urology Congress (March 15–19, 2013; Milan, Italy).

Interpreting the Clinical Significance of Quality of Life Score Changes after Radiotherapy for Localized Prostate Cancer

Background: The assessment of a clinical significance of certain quality of life score changes is often controversially discussed. Materials and Methods: The Expanded Prostate Cancer Index Composite questionnaire was completed before and 3 times after treatment for prostate cancer by 756 patients. Two criteria were considered as a clinically relevant change: score change corresponding to at least ‘very small problem’ from the patient’s point of view; score change with significantly increasing incidence of symptoms. These changes were compared to the 50% of standard deviation (SD) threshold. Results: Patients assess mean changes up to 4 points to be ‘no problem’, suggesting a mean change of 5 points to be the minimal important difference. With increasing score changes significant changes were noticed in an increasing number of items: up to 4 items if scores decreased 5–10 points. Additionally, an increasing percentage of patients were affected. These results correlated well with the 50% of SD threshold. Conclusions: The threshold of 5 points (or 5% of the instrument range) can be interpreted as the minimal important difference of clinical significance. The proposed criteria corresponded well to the distributionbased criterion based on the 50% of SD level.

cfDNA as a Prognostic Marker of Response to Taxane Based Chemotherapy in Patients with Prostate Cancer

PURPOSE Chemotherapy is an integral part of the treatment of castration resistant prostate cancer. With the introduction of new drugs the need to identify nonresponders is increasing. To our knowledge there are no prognostic parameters to date for use upon the initiation of any treatment. MATERIALS AND METHODS cfDNA was isolated from a serum specimen before chemotherapy. Its value was correlated to recurrence-free and overall survival using Kaplan-Meier curves. Univariate and multivariate Cox regression analysis was performed to identify independent predictors. RESULTS Of 59 men 48 (81.4%) had a measurable prostate specific antigen decrease from baseline. Median followup was 15.0 months (range 2.4 to 58.4). The median cfDNA concentration in all men in this study was 27.71 ng/ml (mean 32.64). A threshold of 55.03 ng/ml was significantly associated with a poor prostate specific antigen response of less than 30% (p = 0.005). On univariate and multivariate analysis circulating cfDNA was an independent predictor of overall survival (HR 0.36, 95% CI 0.13-0.97, p = 0.044 and HR 0.34, 95% CI 0.12-0.91, p = 0.032, respectively). Limitations of the study are its retrospective character, and first and second line therapies. CONCLUSIONS Our trial shows that the cfDNA concentration before therapy may be a useful predictive and prognostic biomarker for prostate specific antigen response and survival.

Radical retropubic and perineal prostatectomy for clinically localised prostate cancer in renal transplant recipients.

Abstract Objective: To analyse the functional and oncological outcome of consecutive renal-transplant recipients (RTRs) with clinically localised prostate cancer who underwent radical retropubic (RRP) or perineal (RPP) prostatectomy. Patients and methods: Between January 2000 and July 2011 16 patients underwent RRP (group 1) and seven RPP (group 2). In all, 200 consecutive non-RTRs served as the control group, of whom 100 each underwent RRP and RPP, respectively. The mean (range) interval between renal transplantation and RP was 95 (24–206) months, the PSA at the time of diagnosis was 4.5 (3.0–17.5) ng/mL, and the mean patient age was 64 (59–67) years. Results: The mean follow-up was 39 (RRP) and 48 months (RPP). There was no deterioration in graft function. In group 1, 13 and three patients had pT2a-cpN0 and pT3a-bpN0 prostate cancer, respectively, with a Gleason score of 6, 7 and 8 in 11, three and one patients, respectively. In group 2, three and four patients had pT2a-c and pT3a-b disease, respectively, with a Gleason score of 6 and 7 in two and five, respectively. In both groups one patient had a positive surgical margin and was followed expectantly, and all patients have no evidence of disease. Wound infections developed more often in the RPP group (29% vs. 7%), but there were no Clavien grade III–V complications. All patients achieved good continence, and two need one pad/day. Conclusions: RRP and RPP are suitable surgical treatments for prostate cancer in RTRs. RRP might be preferable, as it has the advantage of simultaneous pelvic lymphadenectomy and a lower risk of infectious complications.