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.

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.

[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.

[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.

[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.

Late oncological occurrences following radical cystectomy in patients with bladder cancer.

PURPOSE: To evaluate the prognoses and predictive factors of late oncological occurrences and its impact on follow-up strategy in patients with bladder tumours treated with radical cystectomy. MATERIALS AND METHODS: Late oncological occurrences were considered when they took place after three years from cystectomy or when early recurrence was controlled with therapy and patients developed recurrence again after a three-year disease-free interval. Univariate and multivariate analysis of predictive factors for late oncological occurrences were carried out on 215 patients at risk of late oncological recurrences. RESULTS: Among 357 patients treated with cystectomy, 163 (45.6%) relapsed, 149 (41.7%) of them as early recurrence and 17 (4.7%) were considered as late oncological events. This incidence increased up to 8% when patients at risk were considered. Three patients with early recurrence reached a complete response after treatment and relapsed again as late recurrences. Distant metastases and local recurrence represented 78.5% of early recurrence as opposed to 11.7% in late oncological occurrences, whereas, extravesical urothelium recurrences represented 8.6% and 70% respectively (p<0.01). Among patients with late oncological occurrences, nine (53%) were disease-free, seven with urothelial recurrence and two of three with lymph-node recurrence whereas only eight (5.6%) patients with early recurrence were free of tumour (p<0.0001). Multiple tumours, prostate involvement and organ-confined tumours in cystectomy specimen were the independent variables for predicting late oncological occurrences in multivariate analysis. CONCLUSIONS: Recurrences in the remaining urothelium prevail as the pattern of late oncological occurrences. The prognosis of these events is significantly better than an early recurrence. Patients at risk of late oncological occurrences are those with multiple tumours, prostate involvement and with organ-confined tumours in cystectomy specimen. After three years from cystectomy, the follow-up schedule of these patients be limited to performing an annual CT-scan and urinary cytology to detect essentially upper urinary tract recurrence and extrapelvic lymph-nodal recurrence. Afterwards an annual intravenous urography might replace to CT-scan since lymph-nodal involvement was not detected.

Clinical panurothelial disease in patients with superficial bladder tumors: therapeutic implications.

PURPOSE: We established the prognostic and therapeutic implications of panurothelial involvement in patients with superficial bladder tumors for optimizing therapeutic approaches in those at risk for panurothelial involvement. MATERIALS AND METHODS: We studied the records of 35 patients with clinical panurothelial disease. Since all of these patients presented with high risk superficial bladder cancer during followup, they were included in specific therapeutic and followup regimens. Radical procedures or conservative therapies were indicated mainly according to pathological examination and the recurrence pattern. RESULTS: Panurothelial involvement was a late stage of a recurrent and diffuse process that essentially developed in sequences, in which all patients presented with high risk superficial bladder tumors. This process involved continued relapse after panurothelial involvement developed. Notably 19 patients (79.1%) at risk for recurrence had repeat relapse in the urothelium. In the upper urinary tract 12 patients (34.3%) had bilateral involvement, including 7 (41.2%) of 17 patients after cystectomy. We identified 2 subgroups of patients. The subgroup with a better prognosis included 27 patients in whom late panurothelial disease developed step by step after a complete response to intravesical therapy, including 14 (51.8%) who were free of disease. The other subgroup with a poor prognosis included 8 patients with concurrent bladder carcinoma in situ and prostate involvement as well as early panurothelial disease, of whom only 2 (25%) were disease-free. All patients underwent many therapeutic approaches. A mean of 7.5 surgical procedures per patient were done, including a mean of 5.5 transurethral resections, a mean of 1 conservative approach to the upper urinary tract and a mean of 1.1 radical procedures. At a median followup of 111 months 10 patients (28.5%) were disease-free but only 7 (20%) retained the bladder, while 19 (54.3%) died of tumor. CONCLUSIONS: Patients with high risk superficial bladder multifocal tumors and associated bladder carcinoma in situ are at high risk for panurothelial involvement. Radical cystectomy may be recommended in these patients when initially or during followup, concurrent high risk superficial bladder tumors and prostate involvement develop or prostate involvement recurs. For the upper urinary tract conservative therapies may be advisable when noninfiltrating tumors are diagnosed even after cystectomy due to the high rate of bilateral new onset disease. When cystectomy is performed, extended excision of the upper urinary tract and pyelo-intestinal anastomosis may be considered.

Effectiveness of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer: short and long-term followup.

PURPOSE: We analyze the impact of a single mitomycin C instillation in patients with low risk superficial bladder cancer with short and long-term followup. MATERIALS AND METHODS: A total of 131 patients with low risk superficial bladder cancer were included in a prospective randomized controlled trial. All patients had a 3 cm or less single, papillary, primary or recurrent tumor and were disease-free for more than 1 year. Patients with muscular invasion, G3 tumor or bladder carcinoma in situ on pathological examination were excluded from study. The tumor was completely resected before patients were randomized into 2 arms of no further treatment (control group) and a single immediate instillation of 30 mg mitomycin C (mitomycin C group). Recurrences were considered early within the first 2 years of followup. RESULTS: At 24-month followup the recurrence-free interval was significantly increased, and recurrence, and recurrence and tumor per year rates were decreased in the mitomycin C compared to the control group. However, at long-term followup these differences were not statistically significant and the recurrence-free interval curves were parallel. A shorter hospital stay and catheterization period were noted in the mitomycin C group compared to the control group, which were not significant. Early recurrences were concentrated in the first year in the control but not in the mitomycin C group. A significant relationship between early and late recurrences was found in the mitomycin C but not in the control group. CONCLUSIONS: Our analysis confirms the positive effect of a single immediate mitomycin C instillation in patients with low risk superficial bladder cancer. This benefit is limited to early recurrence and is not maintained with long-term followup. Thus, this approach is an alternative to observation or endovesical chemotherapy. Our study also suggests that cell implantation as a mechanism of early recurrence can be controlled with a single mitomycin C instillation.

Feasibility of transurethral resection for muscle infiltrating carcinoma of the bladder: long-term followup of a prospective study.

PURPOSE: We analyzed the long-term results of radical transurethral resection for the treatment of a large series of patients with muscle infiltrating bladder cancer entered into a prospective study to determine progression predictive factors. MATERIALS AND METHODS: The study included 133 patients with invasive bladder cancer treated by radical transurethral resection who had negative biopsies of the muscle layer of the tumor bed. Followup was more than 5 years for all subjects and more than 10 years in 59 (44.4%). A comparative nonrandomized study was performed of a control group of 76 patients with invasive pathological stage pT2-3a, N0-3 bladder cancer treated by cystectomy. In those patients treated by radical transurethral resection univariate and multivariate analyses were performed to establish clinical progression predictive factors. RESULTS: At 5 and 10 years of followup cause specific survival rates were 80.5 and 74.5%, and bladder preservation rates were 82.7 and 79.6%, respectively. No significant difference was noted in terms of cause specific survival, with respect to the control group. The initial presence of associated bladder carcinoma in situ was the only independent progression predictive factor. CONCLUSIONS: For patients with invasive bladder cancer radical transurethral resection is justified when the tumor is clinically limited to the muscular layer and when all biopsies of the periphery and depth of the tumor bed show muscular tissue negative for tumor cells. Patients with initial associated bladder carcinoma in situ should not be excluded from this treatment but endovesical bacillus Calmette-Guerin immunotherapy should be administered and a closer followup is recommended.

Extravesical involvement in patients with bladder carcinoma in situ: biological and therapy implications.

PURPOSE: The biological and therapeutic implications of extravesical involvement in patients with bladder carcinoma in situ were analyzed. MATERIALS AND METHODS: Of 138 patients with bladder carcinoma in situ 87 (63%) had extravesical involvement, including the prostate in 53, the upper urinary tract in 11 and both structures in 23 (pan-urothelial involvement). With survival free of disease as an end point, univariate and multivariate analyses were done. RESULTS: Patients with extravesical involvement had worse survival than those with bladder carcinoma in situ alone (p < 0.001). In multivariate analysis prostate involvement (p = 0.0007) and pan-urothelial involvement (p = 0.0001) were selected as significant variables. When pathological patterns were considered prostatic stromal invasion (p = 0.0002) was the only variable selected. With these data 3 patient groups with disease mortality risk were defined. CONCLUSIONS: Prostate involvement and pan-urothelial involvement behave as independent prognostic factors, with the latter probably reflecting an extremetly diffuse character of carcinoma in situ. However, the upper urinary tract had no influence on survival. In patients with upper urinary tract and/or prostatic involvement limited to the mucosa treatment can be conservative. Patients with ductal or stromal involvement should undergo radical treatment. For upper tract involvement conservative approaches may be considered if there are no radiological signs of invasion or low grade tumor.

The prostate involvement as prognostic factor in patients with superficial bladder tumors.

PURPOSE: The prognostic value of prostate involvement in patients with superficial bladder cancer was analyzed. MATERIALS AND METHODS: We studied 96 patients with prostate involvement. Taking progression-free survival rate as an end point, univariate and multivariate analyses were done. RESULTS: The presence or absence of bladder carcinoma in situ is related to poor and good prognoses, respectively (p < 0.001). Stromal invasion (p < 0.001) and pan-urothelial involvement (p = 0.03) were also identified as independent factors of poor prognosis. CONCLUSIONS: Patients with tumor limited to the mucosa can be treated conservatively. Cystoprostatectomy can be performed in patients with ductal involvement. The prognosis of patients with stromal invasion is poor despite radical treatment.

Preservation of antegrade ejaculation in retroperitoneal lymphadenectomy due to residual masses after primary chemotherapy for testicular carcinoma.

We report 18 consecutive patients with testis cancer and retroperitoneal residual masses with normal tumor markers, who underwent lymphadenectomy. Aiming to preserve the antegrade ejaculation, we carried out surgical modifications which basically attempt to preserve: (1) both sympathetic lumbar trunks, (2) the superior hypogastric plexus and (3) some of the postganglionic branches. With a mean follow-up of 28.1 months (range 6-62 months), 15 (83.3%) of the 18 patients preserved ejaculation, without significant differences between ejaculation volumes before and after lymphadenectomy. At the present time, 3 of 4 possible patients have fathered children. Mass size seems to be an important predictive factor of ejaculation preservation. One patient relapsed in the retroperitoneal dissection area, representing a recurrence rate of 5.5%. The disease-free survival rate was 94.4%, and 1 patient died due to disease progression with lung recurrence. Thus preservation of ejaculation was possible in most of these patients.

Feasibility of transurethral resection for muscle-infiltrating carcinoma of the bladder: prospective study.

A prospective study was done to evaluate treatment of patients with muscle-infiltrating bladder cancer by transurethral resection exclusively. Inclusion criteria for this study were histological confirmation of muscular bladder infiltration, endoscopic radical transurethral resection, disappearance of hardened areas after transurethral resection, and negative biopsies of the depth and periphery of the tumor bed. The study began in April 1981. The average followup in series 1 (April 1981 to December 1986, 59 patients) was 55.4 months. Actually, of the patients 31 (52.5%) are without evidence of recurrence and 28 (47.5%) have recurrent disease. Of the latter patients 11 (18.6%) had invasive bladder recurrence, including 7 (11.9%) who had recurrence at 3 months, which indicated clinical understaging. Three patients (5%) had metastases without bladder tumor. The remaining 14 patients (23.7%) had superficial bladder recurrence. The overall survival rate was 83% (49 of 59 patients) and 43 patients (72.8%) still retain the bladder. The present data are confirmed by the results of series 2 (December 1986 to August 1989). Therefore, the data would justify conservative management in a selected group of patients with muscle-infiltrating bladder cancer.

Corpus cavernosum invasion and tumor grade in the prediction of lymph node condition in penile carcinoma.

Of the 101 patients with penile cancer, we have analyzed 66 from whom we had enough information: 42 (63.3%) patients with corpora cavernosa invasion (T2-3) and 24 (36.6%) without (T1). With respect to the tumor grade, in 36 (54.3%) patients it was well differentiated (G I), in 23 (34.8%) moderately (G II) and in 7 (10.6%) poorly differentiated (G III). We also analyzed the inguinal lymph node condition. Of the 66 patients, 28 (42.4%) developed nodal metastases, and 38 (57.6%) were considered free of nodal metastases and disease with an average follow-up of 76.2 months (range 38-192). The presence of metastatic nodes was influenced by both tumor stage and grade with significant differences between T2-3 and T1 (p = 0.001) and between G II-III and G I (p < 0.01), but each of them alone was not a sufficiently reliable predictive factor. In order to associate local stages and tumor grades in relation to the presence of metastatic nodes, we checked that none of the patients with T1, G I (group 1) developed nodal metastases, and therefore, 'wait and see' should be the suitable approach. Twenty (80%) of the patients with T2-3, G II-III (group 2) developed metastatic lymph nodes, thus, in this group, an early lymphadenectomy should be performed. In the remaining 22 patients with T1, G II-III and T2, G I (group 3), 8 (36.4%) showed metastatic lymph nodes; in this group, other factors such as age, cultural level and obesity should be taken into account when deciding on lymphadenectomy.

Recurrence of superficial bladder tumors in prostatic urethra.

Of our 276 patients with superficial bladder carcinoma, 242 were male, and 36 of these had recurrence in prostatic urethra, 26 with macroscopic tumors, and 10 with tumors in situ (TIS). These recurrences represent an incidence of 13.3%, with an average follow-up of 34.3 months. When the urethral tumor was limited to the mucosa, we chose conservative therapy, and the patients entered a random program with Mitomycin or Adriamycin administered endovesically. With this program, we could control the disease in 59.3% of the patients. However, 22.2% of them had recurrence with prostatic stromal infiltration, so that we performed a more exhaustive exploration of the prostate, taking biopsies not only at the 5 and 7 o'clock positions, but also making a wider resection in order to find the incipient infiltration of the prostatic stroma, and trying to avoid a possible understaging. When the urethral tumor had infiltrated the prostatic stroma, we performed cystoprostatourethrectomy, getting a survival rate free of disease of 40%. An association with vesical TIS was detected in 61.1% of these patients, with terminal ureteral tumor in 8.3% and with the anterior urethra in 11.1%, showing the diffuse pattern of the disease. We conclude that when recurrence of prostatic urethra is present, it is necessary to monitor the whole urothelium during follow-up.

Carcinoma in situ associated with superficial bladder tumor.

In a sample of 306 patients with superficial bladder tumors (Ta, Tl), 48 were affected by associated carcinoma in situ (TIS). We included 40 of them in a random program with Mitomycin C or Adriamycin, administered endovesically. We found that those patients with associated TIS whose progression rate had increased to 37.1% compared to 8.8% in the original series (p less than 0.01), had a worse prognosis. Besides, 10 of them required radical cystectomy. With this chemotherapy program, we achieved a high rate of complete response (70%), but its duration was limited by a recurrence rate of 42.9%, with a time free of disease of 26.2 months. In the whole group, the survival rate free of disease was 77.5%, with an average follow-up of 37.3 months. On the other hand, we found extravesical recurrences not only in the prostatic urethra (13; 32.5%) but also at the end of the ureter (3; 7.5%).

[Biological behavior of untreated bladder carcinoma in situ]. / Comportamiento biológico del carcinoma in situ vesical no tratado.

The biological behaviour of initially untreated carcinoma in situ of the bladder was studied in 20 patients. A 35.4-month follow-up revealed a heterogeneous behaviour of this disease entity. Diffuse tumors were clearly distinct from focal tumors. The evolution of the former appeared to be more aggressive: no spontaneous remission was observed, 58.3% remained as such while 41.6% progressed to muscle layer infiltration. Focal tumors evolved more favourably: only 1 (12.5%) developed into diffuse carcinoma in situ, 2 (25%) continued to be positive for cytology, while 4 (50%) remitted spontaneously. We therefore consider that both patient groups must be treated upon diagnosis. Intravesical treatment, which achieves a high rate of complete response, is advocated.

[Stage T4 bladder cancer. Impact of neoadjuvant chemotherapy on T4b tumors]. / Carcinoma vesical estadio T4. Impacto de la quimioterapia neoadyuvante en tumores T4b.

The present article studied the biological behaviour of T4a versus T4b tumors. Of 29 patients with T4a tumors, 24 were treated by radical cystectomy and 5 were treated by diversion alone on detecting pathologic gross adenopathies at laparotomy. Of these 10/28 (35.7%) are alive and tumor-free. Of 11 patients with T4b tumors, 7 were initially treated with systemic chemotherapy (6 M-VAC and 1 5-FU + ADM) which achieved a clinical response in 4; 1 (14.2%) was RCc. Posteriorly, all these patients underwent radical cystectomy that revealed 2 had RPp and 2 had tumor progression (N+), accounting for an RPp rate of 28.5% and tumor progression of 71.5%. Overall, with a mean follow-up of 13.3 months, only 1 patient is tumor free. The foregoing findings show the different behaviour of these two groups of patients with an incidence of tumor positive adenopathies of 48.2% and 72.7% and tumor-free survival of 35.7% and 9.0% for patients with T4a and T4b, respectively.