Daniel Porres

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.

Surgical Resection of Urological Tumor Metastases Following Medical Treatment

BACKGROUND The rate of systemic metastases is about 20% in testicular germ cell tumors, 25% to 30% in prostate cancer, 30% in urothelial carcinoma with muscle invasion, and 50% in renal-cell carcinoma. This article is a critical review of current data on the resection of metastases of urological tumors after systemic drug treatment. METHODS Review of pertinent publications retrieved by a selective literature search. RESULTS No pertinent prospective, randomized trials, meta-analyses, or Cochrane reviews have been published. The publications available for review include guidelines and retrospective studies with evidence levels ranging from IIB to III. For non-seminomatous germ cell tumors with tumor markers that are negative or have reached a plateau after chemotherapy, resection of retroperitoneal, intra-abdominal, and intrathoracic metastases with curative intent is now the treatment of choice at clinical reference centers. For urothelial carcinoma that has gone into partial remission after systemic chemotherapy, with full resectability, the resection of metastases prolongs survival from about 13 months to 31-41 months. For prostatic carcinoma with solitary, intrapelvic lymph-node metastases and PSA less than 4 ng/mL, the resection of metastases prolongs 5-year progression-free survival in 40% to 50% of cases. There is, however, no indication for the resection of retro-peritoneal, visceral, or bony metastases. In renal-cell carcinoma, the resection of pulmonary or hepatic metastases is associated with a 5-year survival rate of 40% to 50% or 62%, respectively, and should thus be made a component of the treatment plan for this disease. The indication for resecting metastases of urological cancers should always be established by an interdisciplinary tumor board in the light of the existing scientific evidence. CONCLUSION The resection of metastases of some types of urological cancer after chemotherapy can prolong progression-free and overall survival. This form of treatment deserves consideration as a component of individual care and of the interdisciplinary treatment plan for urological cancers.

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.

The role of palliative surgery in castration-resistant prostate cancer.

Purpose of reviewAndrogen deprivation therapy with luteinising hormone releasing hormone (LHRH) analogues or antagonists represents the treatment of choice in men metastatic prostate cancer (PCA). Depending on the serum concentration of the prostate-specific antigen (PSA) nadir, the survival might vary between 11 and 78 months. About one-third of all patients without local treatment of the primary will develop significant complications of the lower and upper urinary tract because of local progression of PCA. It is the purpose of the review to inform the treating physician about palliative surgical options in men with castration-resistant prostate cancer (CRPC). Recent findingsIn men with CRPC and lower urinary tract symptoms, palliative transurethral resection of the prostate (TUR-P) can be performed with a 60–70% success rate. Infiltration of the pelvic floor, the bladder neck and trigone and the external urethral sphincter can make palliative radical surgery necessary. Bladder neck closure with continent vesicostomy, radical cystoprostatectomy with an incontinent urinary diversion, and anterior and posterior exenteration are individual therapeutic options in men with a good performance status and a considerable life expectancy. Symptomatic involvement of the upper urinary tract can be managed by placement of endoluminal stents or a percutaneous nephrostomy in men with a poor performance. In men with a good response to androgen deprivation therapy (ADT) and a good performance status reconstructive ureteral surgery might be considered and the options of ureteral reimplantation, ureter ileal replacement and a subcutaneous pyelovesical bypass have to be discussed. SummaryThere are various palliative surgical treatment options in the management of men with CRPC and symptomatic deterioration of the lower or the upper urinary tract, which should be considered in well selected patients. The indication to perform one of the above-mentioned surgical approaches needs to be discussed in a multidisciplinary tumour board.

Robot-Assisted Radical Prostatectomy for the Treatment of Radiation-Resistant Prostate Cancer: Surgical, Oncological and Short-Term Functional Outcomes

Objective: The objective of this study was to assess the surgical, oncological and short-term functional outcomes in patients undergoing salvage robot-assisted radical prostatectomy (SRARP) for the treatment of radiation-resistant prostate cancer. Patients and Methods: The records of 3,500 men who underwent RARP from February 2006 to July 2011 were retrospectively reviewed. All peri- and postoperative data were recorded prospectively in our database. A total of 13 patients (0.37%) who had undergone SRARP for the treatment of radiation-resistant prostate cancer were identified. Results: The primary treatment was external beam radiotherapy in 7 patients (53.8%) and brachytherapy in 6 patients (46.2%). The interval from radiotherapy to biochemical recurrence (BCR) varied from 12 to 108 months (median 48.9). Neurovascular bundle preservation was performed in 3 patients (23.1%). No intraoperative or major complications were encountered. Minor complications were encountered in 4 patients (30.7%). At 12 months, 7 patients were continent (53.8%), 3 exhibited mild incontinence (23.1%) and 3 (23.1%) were incontinent. Regarding potency, none of the patients were potent at 6 months, but 3 patients (23.1%) were potent at 1 year. Regarding BCR, 3 of the patients (23.1%) never reached a prostate-specific antigen nadir of zero, and during the follow-up period only 3 patients (23.1%) exhibited BCR. No disease-specific mortality was evident during follow-up. Conclusions: Although early in its development, it appears that SRARP is technically feasible and offers satisfactory surgical, oncological and short-term functional outcomes.

The Role of Palliative Surgery in Castration-Resistant Prostate Cancer

Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) analogues or antagonists represents the treatment of choice in men with metastatic prostate cancer (PCA). Depending on the serum concentration of the prostate-specific antigen (PSA) nadir, the survival might vary between 11 and 78 months. In castration-resistant PCA (CRPC), all new medical treatment options can induce complete and partial remissions in metastatic foci, but they have no profound effect on the prostate itself, as has been shown recently. About one-third of all patients without local treatment of the primary will develop significant complications of the lower and upper urinary tract due to local progression of the PCA. In men with CRPC and lower urinary tract symptoms, palliative transurethral resection of the prostate (TURP) can be performed with a 60-70% success rate. Infiltration of the pelvic floor, the bladder neck and trigone, and the external urethral sphincter can make palliative radical surgery necessary. Bladder neck closure with continent vesicostomy, radical cystoprostatectomy with an incontinent urinary diversion, and anterior and posterior exenteration are individual therapeutic options in men with a good performance status and a considerable life expectancy. Symptomatic involvement of the upper urinary tract can be managed by the placement of endoluminal stents or a percutaneous nephrostomy in men with poor performance. In men with a good response to ADT and a good performance status, reconstructive ureteral surgery might be considered and the options of ureteral reimplantation, ureter ileal replacement, and a subcutaneous pyelovesical bypass have to be discussed. The indication to perform one of the above-mentioned surgical approaches needs to be discussed in a multidisciplinary tumor board.

Metastasectomy for renal cell cancer

BACKGROUND Metastasectomy prior to or after systemic medical cancer treatment is performed within a multimodal therapeutic approach in metastatic renal cell cancer (mRCC) to improve the prognosis. The role of metastasectomy in mRCC is controversially discussed and the potential therapeutic benefit is unquantifiable. The purpose of the current review is to critically discuss the available data. METHODS A systematic literature search was carried out in the MedLinedatabase to identify original publications, review articles and editorials with respect to metastasectomy in mRCC and the current European guidelines were also taken into consideration. RESULTS Metastasectomy is one of the approaches for mRCC recommended in the guidelines in cases of stable disease for at least 3 months, complete resectability of all metastatic lesions independent of the anatomic localization and a good performance status of the patient. The median survival time varies between 35 and 55 months. CONCLUSIONS In mRCC metastasectomy is an indiviudal therapeutic approach which might be considered for limited metastatic disease and the presence of good prognostic risk factors to improve average survival time. Especially in renal cell cancer metastasectomy should be considered early.

Comparison of second-line treatments in patients with castration-resistant prostate cancer with PSA relapse after or during docetaxel chemotherapy.

243 Background: Docetaxel was the first agent with a proven survival benefit and improved quality of life in patients with castration resistant prostate cancer. Recently there are two new agents, Cabazitaxel (Caba) and Abiraterone Acetate (AA) approved for the second-line treatment in case of progressive disease after Docetaxel. We compared the PSA response and complication rate of these three different second-line treatment options: Caba, AA and Docetaxel Re-Challenge (R-Doc). METHODS The data of 71 patients with progressive disease after/during Docetaxel chemotherapy were analyzed retrospectively. 25 patients with R-Doc, 27 patients with AA and 19 patients with Caba. All patients except two had a PSA-Response or stable disease to primary docetaxel chemotherapy. Mean patient age was 74 years for R-Doc, 71 for AA and 69 for Caba with a mean PSA before initiating treatment of 45 ng/ml, 162ng/ml and 563ng/ml. RESULTS PSA response rates (>50% regression) were seen in 14 (56%), 8 (38%) and 6 (32%) patients respectively. PSA stabilization was seen in 7 (28%), 2 (9,5%) and 7 (36,8%) patients. Haematologic complications grade >=3 were seen more frequently in R-Doce (32%) and Caba (42%) compared to AA (4%). Cardiovascular complications >= grade 3 were seen in 30% of the patients with AA whereas none of the patients with R-Doc or Caba had cardiovascular grade 3 or 4 side effects. CONCLUSIONS With AA, Caba and the possibility of R-Doc there are compareable treatment options with regard to PSA response rates, even if a stable disease can be seen more frequently in Caba and R-Doc. As the drugs have different side effects the first second line treatment should be considered to the patients characteristics and comorbidity in the palliative setting. PSA progression free survival and overall survival data are awaited.

Sextant-Specific Analysis of Detection and Tumor Volume by HistoScanning™.

Introduction: Published results of HistoScanning™ (HS) for prostate cancer (PCa) diagnostics are inconsistent and their value remains unclear. We prospectively analyzed the detection rate and tumor volume concordance in PCa patients. Material and Methods: Two hundred and eighty-two patients with biopsy-proven PCa scheduled for radical prostatectomy (RP) were included. All patients underwent ultrasonographical examination by HS prior to surgery. HS was evaluated compared to RP specimen as to (1) the prediction of overall tumor volume and (2) accuracy of HS in detection of PCa lesions larger than 0.2/0.5 ml, separated for each sextant. For each sextant, receiver operating characteristic (ROC)-analysis and area under the curve were determined. Sensitivity and specificity were calculated and visualized in ROC-curves. Results: HS tends to underestimate volume of cancerous lesions, particularly larger lesions >8 ml. Using a 0.2 ml detection threshold, specificity and sensitivity of HS were between 29-68% and 46-78%. For a 0.5 ml detection threshold, sextant-specific specificity increased to 59-92% and sensitivity decreased to 16-54%. Stratification according to pre-operational PSA values did not improve performance characteristics of HS. Conclusions: Our results do not support a significant contribution of HS to PCa diagnostics.