Prostatectomy pathology findings in an active surveillance population.

OBJECTIVES: The difficulty in predicting indolent prostate cancer leads to the use of different inclusion criteria in an active surveillance (AS) program. This chapter presents the pathology findings of radical prostatectomy (RP) in patients whose disease meet criteria for AS, as well as of those who are operated during AS. METHODS: Two independent Medline searches were conducted, both of them with a double objective: pathological findingsin radical prostatectomy specimens of patients who could have been included in AS and pathological features of patients operated after an AS period. The following terms were used for the research: "prostaticneoplasm", "radical prostatectomy" and "active surveillance": "radical prostatectomy", "after", "following" and "active surveillance". Pathological findings in radical prostatectomy specimens, down staging and downgrading rates were recorded. Active surveillance length and reason for surgery was included when it was available. RESULTS: Depending on different AS inclusion criteria, clinical downgrading rate (pathological Gleason > 6) varied between 12.1 and 61% and clinical downstaging between 0-26%. Pathological Gleason score =8 was reported in 0-7.8% and there were anecdotal findings of seminal vesicle invasion or positive nodes. Overall, unfavorable pathology (Gleason ≥ 7 or stage ≥ pT3)was detected in 13.1-42.4%, based on different definitions. The criteria at John Hopkins were the strictest and had the lowest clinical downgrading and downstaging. On the other hand, the Memorial Sloan Kettering Cancer Center(MSKCC) criteria had the highest risk of unfavorable pathology but had the highest recruitment capacity. Indolent tumor was observed in 70-82.2% according to the current definition. The average duration in AS prior to surgery was 15-37 months. pT3 stage was seen in 7.7-36.7%, Gleason score 3+4 in 18.6-42.9%, Gleason score 4+3 in 1.4-31.8%, Gleason score >7 in 0-10.3%, positive margins in 3-40.9%. Seminal vesicle invasion rate was extremely low (0-2.9%) as well as positive nodes (0-4.5%). CONCLUSIONS: Although there is a low risk of clinical downstaging and downgrading between patients who have being included in AS, it remains feasible. The probability of predicting an indolent tumor depends greatly on the quality of the prostate biopsy and/or the confirmatory biopsy. On the other hand, most patients who progress in an AS program can have a high probability of cure. We are still in the early stages of AS management in order to be able to predict the biological behavior and the cure rate of radical prostatectomy in patients after a long AS period.

[Is radical cystectomy justified in patients over 75 years old?]. / Está justificada la cistectomía radical en pacientes mayores de 75 años?

INTRODUCTION AND OBJECTIVES: Radical cystectomy is the standard treatment for invasive bladder cancer. The objectives are to evaluate intraoperative and postoperative complications and to determine overall disease-free interval and overall time to progression in patients over tha age of 75 and to compare these with younger patients. MATERIAL AND METHODS: Between august 1980 and october 2004 , 495 patients underwent radical cistectomy. Patients with palliative surgery were excluded. Patients were divided in two groups according to age: control group (<75 years old) and elderly group (> or =75 years old). RESULTS: Four hundred and two patients were evaluated: 39 patients (35 male and 5 female) in the elderly group and 363 in the control group (321 males and 42 females). Mean age was 76 (range: 75-82) and 62 (range: 35-74) respectively. Mean followup was 38 months in the elderly group and 64 months in the control group. Thirty one patients (80.4%) in the elderly group and 211 patients (58.2%) in the control had non organ-confined tumour in cystectomy specimen (pT3-pT4) (p=0.0096) and ten patients (28.6%) in the elderly and 111 patients (31.4%) in the control group had positive nodes (p=0.84). There were no differences in postoperative surgical complications (p=0.08), postoperative reoperation rate (p=0.58) and postoperative mortality (p=0.28) in both groups. During postoperative time, 11 patients (28%) in the elderly group and 50 patients (13.8%) in the control had medical complications (p=0.03). Fourteen patients (35.9%) in the elderly group and 104 patients (39.4%) in the control group died due to tumour during follow-up (p=0.73). Kaplan-Meier survival curve revealed no differences between two groups in overall disease-free interval and overall time to progression. CONCLUSIONS: Radical cystectomy is a safe and effective treatment in elderly patients with invasive bladder cancer. It is necessary to evaluate co-morbidity in this group because there is an increase in postoperative medical complications. There were no differences between the two groups in overall disease-free interval and overall time to progression.

Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital. / Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico.

OBJECTIVES: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. MATERIAL AND METHODS: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. RESULTS: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. CONCLUSIONS: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase.

Preliminary results of the Spanish Association of Urology National Registry in Active Surveillance for prostate cancer.

OBJECTIVES: To present a National Registry of patients with prostate cancer as monitored through active surveillance, with the intention of testing the hypothesis that cancer-specific mortality in very low-risk and low-risk patients is less than 5% at 15 years. MATERIAL AND METHODS: A multicentre observational study (AEU-PIEM/2014/0001) sponsored by the Spanish Association of Urology was conducted using their platform for multicentre studies. The clinical-pathological inclusion criteria were as follows: cT1a-cT3a, PSA ≤ 20 ng/ml, initial minimum biopsy of 10 cores, number of affected cores ≤ 3, 1st Gleason score of 3 and 2nd Gleason score ≤ 4 and a known prostate volume (in cc). A unified follow-up was not established for all recruiting centres; however, a survey was conducted that reflects the follow-up characteristics based on a number of tangible parameters that allow for their comparison. With the same philosophy of flexibility, the use of certain biomarkers and multiparametric MRI was not considered necessary for inclusion. RESULTS: We describe the Registry's characteristics and possibilities, as well as the preliminary results from the 324 patients included in its first 5 months of operation in the 15 recruiting centres. We also report the clinical-pathological variables, biomarkers, radiodiagnosis technique and quality-of-life questionnaires considered for the database, as well as the possibilities for indefinite follow-up, remaining open to any active treatment recognized in clinical guidelines. CONCLUSIONS: The AEU-PIEM/2014/0001 represents an extremely useful tool for all Spanish urologists for multicentre clinical research. The registry will undoubtedly enable the dissemination of active surveillance of our patients in a more coordinated manner, thus maintaining the advantages of optimised opportunistic screening for prostate cancer without resulting in overtreatment.

Assessment and clinical factors associated with pain in patients undergoing transrectal prostate biopsy.

OBJECTIVES: To quantify the degree of pain experienced by patients who undergo ultrasound-guided transrectal prostate biopsy in standard clinical practice and assess the clinical factors associated with increased pain. MATERIAL AND METHODS: Analysis of a multicenter series of patients with prostate biopsy according to standard clinical practice. The biopsy was performed transrectally with a protocol of local anesthesia on the posterolateral nerve bundle. The pain was assessed at 20minutes into the procedure using the visual analog scale (0-10). The degree of pain was analyzed, and the association was studied using a univariate/multivariate analysis of selected clinical variables and the degree of pain. RESULTS: A total of 1188 patients with a median age of 64 years were analyzed. Thirty percent of the biopsies were diagnosed with a tumor. The median pain score was 2, with 65% of the patients reporting a pain score ≤2. The multivariate analysis showed that the prostate volume (RR, 1.34; 95% CI 1.01-1.77; P=.04), having a previous biopsy (RR, 2.25; 95% CI 1.44-3.52; P<.01), age (RR, .63; 95% CI .47-.85; P<.01) and feel palpation (RR, 1.95; 95% CI 1.28-2.96; P<.01) were factors independently associated with greater pain during the procedure. CONCLUSIONS: Transrectal biopsy with local anesthesia is a relatively painless technique. Factors such as age, a previous biopsy, pain on being touched and prostate volume were associated with the presence of greater pain during the procedure.

Upper urinary tract involvement in patients with bladder carcinoma in situ (Tis): its impact on management.

OBJECTIVES: To analyze the biologic behavior and etiologic mechanism of upper-tract involvement in patients with bladder cancer in situ (Tis) and its impact on management of these patients. METHODS: One hundred thirty-eight patients with bladder Tis, 786 with superficial bladder cancer, and 179 patients with invasive bladder cancer treated by cystectomy were studied: 34 (24.6%), 18 (2.3%), and 7 (3.9%) developed upper-tract involvement in each group, respectively. Sixty-three patients with primary urothelial upper-tract tumors were also studied. Taking progression-free survival as an end point, univariate and multivariate analyses were performed. RESULTS: The upper-tract recurrence rate was significantly higher in patients with bladder Tis than in patients with superficial bladder tumors (P <0.001); it was also significantly higher in patients treated with cystectomy because of bladder Tis compared with those treated because of invasive tumors (P <0.01). Patients with bladder Tis and upper-tract involvement showed high rates of upper-tract bilaterality (32.3%) and prostate involvement (67.4%). On pathologic examination, the upper tract showed predominantly superficial (Ta-T1-Tis) tumors (67.4%) and distal ureter location as the only finding (47%). In patients with bladder Tis, upper-tract involvement alone does not have a negative impact on the survival rate according to univariate and multivariate analysis (P = NS). CONCLUSIONS: In patients with bladder Tis, upper-tract involvement represents a diffuse process; therefore, a close evaluation of both the prostate and the upper tract is recommended. Upper-tract involvement has no impact on bladder-preservation strategy. Many of these patients could also be offered a conservative management for the involved upper tract.

[Treatment of metastatic prostatic cancer with monthly injections of leuprolide acetate depot]. / Tratamiento del cáncer prostático metastásico con inyección mensual de leuprolide acetato depot.

Seventy-two patients were admitted in a multicentre trial with the purpose of assessing the clinical efficacy and safety of the hormonal control and tolerance of leuprolide acetate in a once-a-month depot injection formulation for the treatment of disseminated prostate cancer. During a 1-year follow-up, there were ten withdrawals for different reasons. At baseline and at 6 months of treatment the following parameters were evaluated: clinical examination, routine blood analysis, PAP, PSA, LH and testosterone, as well as bone scan. LH and testosterone determinations were repeated at 2, 4, 8, 12, 16, 20 and 24 weeks. Testosterone reached castration levels within the second week and was maintained until the end of the study. In agreement with the NPCP criteria, 65 patients were assessed as: complete response 3%, partial response 40%, disease stabilization 36%, and progression 21%. In summary, a once-a-month injection of leuprolide acetate offers a safe and effective alternative to surgical castration.

Radical prostatectomy is a reasonable treatment for patients over 70 years of age.

OBJECTIVE: To compare the tumor nature and oncological course of patients operated on by radical prostatectomy in three age groups. MATERIAL AND METHOD: From the prospective completion of the data base of our department, we analyzed 1012 patients operated on between 1986 and December 2009. Patients with neo- or adjuvant treatment and those with pre-operative PSA over 50 were excluded. The sample was divided into three groups: younger than 60, 60 to 69 and over 70. The clinical, pathological variables, biochemical course and need for rescue treatment were analyzed. We consider biochemical relapse as when the PSA values reached values greater than 0.4 in two consecutive measurements. Rescue was defined as the need for hormone treatment or radiotherapy. We then made a comparative study, a univariate survival analysis by Kaplan and Meyer Curves and multivariate by Cox's regression. RESULTS: The median follow-up was 55.1 months. Of the 1012 patients included in the study, 317 patients (31.3%) had biochemical progression and 259 (25.6%) required rescue treatment. We observed that the groups with the older age had a significantly higher PSA and higher stages than the rest. No differences were observed in the Gleason score of the surgical specimen or in the state of the surgical margins. Biochemical relapse free survival at 5 years was 72.3% (CI 66.4-78.2) in patients under 60 years, 65.3% (CI 60.6-70.0) for patients under 70 and 62.2% (CI 53.2-71.1) for patients of 70 years or older; P<.05. In the univariate study, age was a factor that was significantly associated to biochemical relapse. However, it loses interest in the multivariate study and PSA, pathological state and Gleason score regain interest. Rescue treatment free survival did not differ by age groups. CONCLUSIONS: In the current study, worse biochemical evolution of patients over 70 was observed. However, this worse biochemical course was conditioned by clinically more aggressive tumors that, in our opinion, justifies the decision made in regards to the surgical approach taken with these patients.

Optimizing prostate cancer screening; prospective randomized controlled study of the role of PSA and PCA3 testing in a sequential manner in an opportunistic screening program.

OBJECTIVES: To reduce unnecessary biopsies (Bx) in an opportunistic screening programme of prostate cancer. MATERIAL AND METHODS: We perform a prospective evaluation of PCA3 as a second line biomarker in an opportunistic screening for prostate cancer (PCa). From September-2010 until September-2012, 2,366 men, aged 40-74 years and with >10 years life expectancy, were initially screened with PSA/digital rectal examination (DRE). Men with previous Bx or with recent urine infections were excluded. Men with abnormal DRE and/or PSA >3 ng/ml were submitted for PCA3. All men with PCA3 ≥ 35 underwent an initial biopsy (IBx) -12cores-. Men with PCA3 < 35 were randomized 1:1 to either IBx or observation. Re-biopsy(16-18 cores) criteria were PSA increase >.5 ng/ml at 4-6 months or PSAv > .75 ng/ml/year. RESULTS: With median follow-up (FU) of 10.1 months, PCA3 was performed in 321/2366 men (13.57%), 289 at first visit and 32 during FU. All 110 PCA3+ men (34.3%) were biopsied and PCa was identified in 43 men in IBx (39.1%). In the randomized arm, 110 were observed and 101 underwent biopsy, finding 12 PCa (11.9%), showing a statistically significant reduction of PCa detection rate in this cohort (P<.001). Global PCa detection rates were 40.9% and 9.5% for the PCA3+ and PCA3- branches, respectively (P<.001). Area under the curve for PSA and PCA3 were .601 and .74, respectively. This is an ongoing prospective study limited by its short follow-up period and still limited enrolment. CONCLUSIONS: PCA3 as a second line biomarker within an opportunistic dual screening protocol, can potentially avoid 65.7% and 50.1% biopsies at first round and at median FU of 10.1 months, respectively, just missing around 3.2% of high grade PCa.

Obligatory information that a patient diagnosed of prostate cancer and candidate for an active surveillance protocol must know.

OBJECTIVES: To know the necessary information to reproduce the results found in the literature on active surveillance (AS) in prostate cancer (PCa) in our own center so that the information would be objective and correctly given to the patients. We have aimed to study the percentage of candidates for AS chosen in our setting, and the data on infrastaging, subgrading and prediction of insignificant PCa, debugging the predictive value of clinical variables to improve our selection criteria and finally to analyze the results of our patients enrolled in AS. MATERIALS AND METHODS: A retro- and prospective review of our data bases was performed. A one-year period was analyzed to know AS candidates. Analysis of our radical prostatectomy specimens for infrastaging, subgrading and prediction of insignificant PCa (Epstein's criteria) was made as well as a uni/multivariate analysis of clinical variables in patients with insignificant PCa in the specimen. A prospective validation was performed with overall survival and survival free of active treatment (SFAT) as endpoints in patients enrolled in AS. RESULTS: Between October-2010/October-2011, 44.7% of our PCa were candidates for AS, but only 11.2% choose it. The percentages found for infrastaging, subgrading and prediction of insignificant PCa were 14%, 31.4% and 55.7%, respectively. However, only just 6 patients (6.97%) had≥pT3a+Gleason≥7+volume>0.5cc PCa. The multivariate analysis showed that PSA density and number of affected cores were independent predictors of insignificant PCa. With a mean follow-up of 36±39months, 63 out of 232 patients enrolled in AS went on to active treatment (27.1%), with only 13 due to anxiety without pathologic progression. Median time of SFAT was 72.7 months (CI 95% 30.9-114.4). SFAT at 24 months was 76.4% (69.7-83.1%) and at 48 months 58.1% (48.8-67.4%). Only 10 patients died (4.3%), 9 due to causes different of PCa. Estimated overall survival at 5 years was 92.8% (CI 95% 86.7-98.9%). CONCLUSIONS: It should be mandatory to have the exact knowledge of the local data of each Center in order to objectively inform patients about prostate biopsy efficiency, and if percentages of infrastaging, subgrading and prediction of insignificant PCa are in accordance with the literature. At 3 years, we reproduced the results of the longest series of AS, so we have ascertained that our AS protocol can be implemented with increasingly more patients.

Margin status is a very important prognostic factor for patients with pT3b prostate cancer.

OBJECTIVE: Despite early diagnosis of prostate cancer, seminal vesicle invasion is still a common clinical scenario nowadays. The objective of this study is to evaluate clinical and pathological prognostic factors in that subgroup of patients. MATERIAL AND METHODS: After approval of our Ethical Committee, we selected all pT3b prostate cancer patients operated between 1987 and 2010. Neoadjuvant treatment patients were excluded. The biochemical free survival periods BFS and the period free of complementary treatment were calculated with the Kaplan Meier method. Cox regression model was used to select those variables associated with biochemical failure and the need for complementary treatment. We considered complementary treatment when radiotherapy or hormone therapy in an adjuvant or salvage scheme was required. RESULTS: 101 patients were selected from 1470 procedures. Among these, 28 patients died (27,7%), 18 due to tumor, and 74 showed biochemical relapse (73,3%). The median follow up was of 4 years and 4 months. The five years BFS was 30.2% (IC 95%: 20.2-40.1), whereas the 5 year period free of complementary treatment was 16.9% (IC 95%: 8.1-25.8%). In the multivariate analysis, margin status (R) was independently and significantly associated with biochemical relapse and the need for complementary treatment. Likewise, the preoperative PSA was associated to biochemical relapse and N1 tumours were clearly associated to complementary treatment. CONCLUSION: pT3b prostate cancer patients with R1 disease have a worse biochemical prognosis and higher probability of complementary treatment.

[Hexaminolevulinate photodynamic diagnosis in non-muscle invasive bladder cancer: experience of the BLUE group]. / Diagnóstico fotodinámico con hexaminolevulinato en el cáncer vesical no músculo invasivo: experiencia del grupo BLUE.

OBJECTIVES: Photodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area. MATERIAL AND METHODS: Fluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients. RESULTS: A total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL. CONCLUSIONS: Hexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD.

[Reconstruction of the glans with free-skin graft applying the Bracka technique]. / Reconstrucción del glande con injerto cutáneo libre según técnica de Bracka.

INTRODUCTION: We analyse our experience in the conservative surgical management of penile cancer and/or penile skin pathologies at our institution. MATERIAL AND METHODS: We have retrospectively reviewed all the skin grafting procedures performed in penile surgery in the last eight years. We show the indications and results of these surgical procedures and the detailed surgical technique originally described by Bracka. RESULTS: Ten patients had several types of partial penile removal surgery followed by free-skin graft resurfacing, creating a neoglans. There were no relevant or major complications; two patients suffered partial necrosis of the skin graft. There was no local recurrence. 6 Patients returned to normal sexual activity after complete healing. CONCLUSIONS: There is a significant number of patients with penile cancer and/or other penile skin pathologies who can undergo definitive and non-mutilating surgery with excellent oncologic, cosmetic and functional results with skin grafting.

[Outcomes of expanded use of PCA3 testing in a Spanish population with clinical suspicion of prostate cancer]. / Resultados del uso expandido del PCA3 score en una población española con sospecha de cáncer de próstata.

OBJECTIVES: DD3(PCA3) (PCA3) gene expression is prostate cancer-specific. Routine use of this biomarker has resulted in a 35-67% reduction in the number of required biopsies. The aim of this study is to evaluate our outcomes in its routine use and to establish in which group of patients this is the most efficient, depending on the number of previous PCA3 biopsies. MATERIAL AND METHODS: A total of 474 consecutive patients who had previously undergone a biopsy (group A, n=337) or not (group B, n=134) for whom a PCA3 was requested were analyzed. We subdivided group A into A(1) (a previous biopsy, n=182) and A(2) (<1 previous biopsy, n=155). The recommendation of whether to perform a biopsy or not was made independently by each of the 11 clinicians and guided by prostatic specific antigen (PSA) levels and digital rectal examination. RESULTS: Median age was 65 years (range 38 to 84). PCA3 score had an informative ratio of 99.6%, with a median of 29 (range 1-3245). The percentage of biopsy sparing was 49% of the cases. ROC analysis demonstrated an AUC for PSA and PCA3 of 0.532 (P=.417) and 0.672 (P<.0001), respectively. Sensitivities of PSA≥ 4 and PCA3≥ 35 were 87% vs. 85%, with specificities of 12% vs. 33%, PPV 34% vs. 39% and NPV 63% vs. 81%, respectively. The PCA3 score showed direct correlation with the percentage of positive biopsies (P<.0001). CONCLUSIONS: Routine use of PCA3, due to its high NPV, results in a significant reduction in the number of biopsies. PCA3 appears to be more efficient in biopsy-naive patients. Among patients already biopsied, the results are superior in those biopsied only once.

[Immunohistochemical expression of microvascular density and carbonic anhidrase IX in renal carcinoma. Relation to histological type and tumoral progression]. / Expresión inmunohistoquímica de la densidad microvascular y de la anhidrasa carbónica IX en carcinoma renal. Relación con el tipo histológico y con la progresión tumoral.

PURPOSE: to correlate the immunohistochemical expression of microvascular density (MVD) and the carbonic anhydrase IX (CAIX) with the different histological subtypes of renal carcinoma and its progression. MATERIAL AND METHODS: we studied 93 patients with renal cell carcinoma operated between 1990 and 2008. Antibodies employed for immunohistochemistry (IHC); CD31 (1: 40, Dako) and CD34 (1: 50, Dako) for MVD and CAIX (1: 100, Santa Cruz). CAIX was validated semiquantitatively as: strongly positive (>85%); weakly positive (10% -85%); and negative (< 10%), independently of the intensity of the stain. MVD was validated with both anti-CD31 and anti-CD34 by means of a whole section, to select the microscopic field (x100) with highest density of stained vessels, counting the number of vessels in a photographic field of 0.53 mm(2). Results are expressed as the maximal number of vessels by mm(2) of tumour tissue. RESULTS: median follow up was 40 months (1-160). We found no differences of expression with any of the 3 IHC markers between tumours that progressed (49) and tumours that did not progress (44). The IHC expression of CAIX was strongly related to MVD, measured for both CD31 and CD34 (p<0.0001). MVD with both antibodies was inversely related to tumour size and Fuhrman grade and was also stronger in clear cell carcinomas compared to the rest of histological subtypes, measured by CD31 (p = 0.001) and CD34 (p = 0.003). CONCLUSIONS: neither MVD nor CAIX expressions were related to tumour progression, but were related to histological subtypes. This fact, added to their co-expression, could prompt the use of the CAIX expression, which is far more reproducible, as a quick and easy approximation to MVD. More research should be done to use it as marker for targeted therapy.

[Metastatic progression, cancer-specific mortality and need for secondary treatments in patients with clinically high-risk prostate cancer treated initially with radical prostatectomy]. / Progresión metastática, mortalidad cáncer específica y necesidad de tratamientos de segunda línea en pacientes con cáncer de próstata de alto riesgo tratados inicialmente mediante prostatectomía radical.

PURPOSE: To determine our results in high risk (HR) prostate cancer (PCa) patients treated with radical prostatectomy (RP) and to establish preoperative prognosis factors. MATERIAL AND METHODS: Retrospective study of 925 RP. Mean follow-up for the HR group was 89.8+/-53.6 months. Following NCCN criteria, we operated 210 (22.7%) HR and 715 (77.3%) low/intermediate risk patients. End point was metastatic progression. Kaplan-Meier method for survival comparison among groups and Cox regression model for multivariate analysis of preoperative prognostic factors were used. RESULTS: Revised period; 1986-2007. Fifty-four patients (25.7%) were free of disease and 8 patients (3.8%) died for other causes free of disease. Disease progressed in 148 patients (70.5%); death due to tumour progression occurred in 42 cases (20%) and due to other causes in 25 patients (11.9%). Seventy-nine patients in HR group (38%) vs 549 low/intermediate risk group (78.5%) did not deserve further treatments (p<0.001). The uni and multivariate analysis for metastatic progression showed both Gleason score at biopsy (RR=1.922; 95% CI 1.106-3.341, p=0.020) and clinical stage (RR=2.290; 95% CI 1.269-4.133, p=0.006) showed independent prognostic value for metastatic progression, but not PSA. CONCLUSIONS: A HR patient can be cured in a third of the cases and will need multimodal treatments in more than half of the times. We prompt surgery in a young healthy patient with a resectable tumour, mainly if just one bad prognostic factor is present and defiantly if this is just PSA elevation.

Resultados oncológicos a largo plazo del tratamiento cáncer de próstata de alto riesgo mediante prostatectomía radical en un hospital oncológico / Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital

Objetivos: Analizar los resultados oncológicos más relevantes en el tratamiento mediante prostatectomía radical (PR) en el cáncer de próstata de alto riesgo (CPAR) en un hospital oncológico. Material y métodos: Estudio retrospectivo descriptivo de las PR realizadas en nuestro centro desde 1986 a 2017 en CPAR para conocer como objetivo primario las supervivencia global (SG) y cáncer específica (SCE), y como objetivos secundarios las supervivencias libre de progresión bioquímica (SLPB), libre de progresión metastática (SLPM), la necesidad de tratamiento de rescate (SLTR), la necesidad de hormonoterapia (SLHT) y finalmente el desarrollo de cáncer de próstata resistente a la castración. Se realizan análisis de regresión de Cox para establecer modelos predictivos y conocer el peso de cada variable definitoria de alto riesgo. Resultados: Se realizaron 2.093 PR de las cuales 480 (22,9%) fueron en CPAR. La mediana de seguimiento de la serie global fue 79,57 meses (P25-75 37,92-135,16). No se realizó linfadenectomía (LDN) en el 6,5% de los casos, mientras que fue LDN obturatriz en 51,2% y extensa en 42,3%. La SG a 5, 10 y 15 años fue de 89,8% (IC 95%: 86,7-92,9%), 73,3% (IC 95%: 68-78,6%) y 51,4% (IC 95%: 43,8-59%). La SCE a 5, 10 y 15 años fue de 94,8% (IC 95%: 92,4-97,2%), 84,0% (IC 95%: 79,3-88,7%) y 75,5% (IC 95%: 68,8-82,2%) La SLPM a 5, 10 y 15 años fue de 87,4% (IC 95%: 84,1-90,7%), 72,2% (IC 95%: 66,7-77,7%) y 61,7% (IC 95%: 54,3-69,1%) respectivamente. Se requirió radioterapia de rescate en 120 pacientes de 477 analizados (25,1%) y 293/477 nunca han requerido hormonoterapia (61,4%). En relación con el uso de HT en los 93 pacientes pN1, 33 (35,5%) no la han necesitado. El tiempo desde la PR a la progresión bioquímica es la variable de mayor peso pronóstico para la SLPM, la SCE y la SG. Conclusiones: La PR más LDN extensa debería ser la primera maniobra terapéutica cuando es factible dentro de una estrategia multimodal. Es necesario un seguimiento mayor de la serie para validar la hipótesis de unos mejores resultados oncológicos basándose en una aplicación más precoz de la RT de rescate, una LDN extensa y los fármacos prolongadores de supervivencia en la fase de CPRC

Objectives: To analyse the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. Material and methods: A descriptive retrospective study of RP was conducted at our centre from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. Results: A total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25-75 37.92-135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7-92.9%), 73.3% (95% CI 68-78.6%) and 51.4% (95% CI 43.8-59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4-97.2%), 84.0% (95% CI 79.3-88.7%) and 75.5% (95% CI 68.8-82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1-90.7%), 72.2% (95% CI 66.7-77.7%) and 61.7% (95% CI 54.3-69.1%), respectively. A total of 120 patients of 477 analysed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. Conclusions: RP plus extended lymphadenectomy should be the first therapeutic manoeuvre when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase

Diagnóstico fotodinámico con hexaminolevulinato en el cáncer vesical no músculo invasivo: experiencia del grupo BLUE / Hexaminolevulinate photodynamic diagnosis in non-muscle invasive bladder cancer: experience of the BLUE group

Objetivos: El diagnóstico fotodinámico (DFD) con hexaminolevulinato se ha empezado a utilizar recientemente para mejorar la detección del cáncer vesical no músculo invasivo. Nuestro objetivo principal fue comparar el rendimiento diagnóstico de DFD frente a endoscopia con luz blanca convencional (LB) en nuestro medio. Material y métodos: Se realizó cistoscopia fluorescente con hexaminolevulinato en el momento de la RTU a 305 pacientes de 7 hospitales españoles. Todas las lesiones detectadas con LB y DFD fueron enumeradas y registradas en una base de datos online. Se analizó histopatológicamente cada lesión por separado. En 148 pacientes se tomaron además biopsias múltiples aleatorias (BMA). Resultados: Se biopsiaron un total de 1.659 lesiones: 522 identificadas con DFD y LB, 237 sólo con DFD, 19 sólo con LB y 881 BMA. De 600 neoplasias diagnosticadas DFD detectó 563, LB 441 y BMA 29 (20 CIS). La tasa media de sobredetección de DFD sobre LB fue del 31,9% globalmente, pero en el caso del CIS fue del 209%. La sensibilidad de DFD fue 93,8% y la de LB 78,2%. La especificidad de DFD fue 81,5% y la de LB 90,5%. En el 23% de los pacientes se detectó al menos una lesión neoplásica más con DFD que con LB. Conclusión: La RTU con hexaminolevulinato mejora el rendimiento diagnóstico y la calidad de la resección del cáncer vesical superficial, especialmente del CIS. La mayor sensibilidad de DFD es a costa de una menor especificidad. En nuestro estudio BMA rescató algunos falsos negativos de DFD para detectar CIS (AU)

Objectives: Photodynamic diagnosis (PDD) with hexaminolevulinate has been recently used to improve detection of non-muscle invasive bladder cancer. Our main purpose was to quantify the benefit of PDD vs. conventional white light cystoscopy (WL) in our area. Material and methods: Fluorescence-guided cystoscopy using hexaminolevulinate was performed at the time of the transurethral resection (TUR) in 305 patients from 7 Spanish hospitals. All lesions found with WL and PDD were numbered and recorded in an online database. Each lesion was sent separately for pathology analysis. Random biopsies were also obtained in 148 patients. Results: A total of 1659 lesions were biopsied: 522 were identified with PDD and WL, 237 only with PDD, 19 only with WL and 881 random biopsies. Of the 600 tumors, PDD detected 563, WL 441 and random biopsies 29 (20 CIS). The mean overdetection rate for PDD over WL was 31.9% for all types of lesions, but it was 209% for carcinoma in situ (CIS). Sensitivity was 93.8% for PDD and 78.2% for WL. Specificity was 81.5% for PDD and 90.5% for WL. In 23% of patients, PDD detected at least one additional neoplastic lesion compared to WL. Conclusions: Hexaminolevulinate fluorescence cystoscopy improves detection and resection of non-muscle invasive bladder cancer, especially of CIS. Sensitivity of PDD is higher than WL, but specificity is lower. In our study, random biopsies were able to detect some CIS not visible under PDD (AU)