Genetic counseling in prostate cancer: How to implement it in daily clinical practice? / Asesoramiento genético en cáncer de próstata: ¿cómo implementarlo en la práctica clínica diaria?

Prostate cancer plays an undeniably prominent role in public health in our days and health systems. Its epidemiological impact is quantitatively very close to that of other tumors such as colon cancer and breast cancer, in which genetic counseling is part of their routine clinical practice, both in the initial evaluation and in the selection of therapeutic strategies. Hereditary cancer syndromes, breast/ovarian and Lynch syndrome are part of genetic counseling in these tumors. Currently, we also know that they can be associated to prostate cancer. The time has come to implement genetic counseling in prostate cancer from the earliest stages of its approach, from initial suspicion to the most advanced tumors. We present an updated review carried out by our interdisciplinary working group on scientific literature, clinical practice guidelines and consensus documents, aimed at the creation and drafting of a'Protocol for genetic counseling in prostate cancer' for the study of germline, with easy application in different healthcare settings. This protocol is currently being implemented in our routine practice and provides answers to 3 specific questions: Who should receive genetic counseling for prostate cancer? Which gene panel should be analyzed? How should counseling be done according to the results obtained? Other aspects about who should perform genetic counseling, ethical considerations and regulations are also collected.

A Preliminary Study of the Ability of the 4Kscore test, the Prostate Cancer Prevention Trial-Risk Calculator and the European Research Screening Prostate-Risk Calculator for Predicting High-Grade Prostate Cancer.

INTRODUCTION: To prevent the overdiagnosis and overtreatment of prostate cancer (PC), therapeutic strategies have been established such as active surveillance and focal therapy, as well as methods for clarifying the diagnosis of high-grade prostate cancer (HGPC) (defined as a Gleason score ≥7), such as multiparametric magnetic resonance imaging and new markers such as the 4Kscore test (4KsT). By means of a pilot study, we aim to test the ability of the 4KsT to identify HGPC in prostate biopsies (Bx) and compare the test with other multivariate prognostic models such as the Prostate Cancer Prevention Trial Risk Calculator 2.0 (PCPTRC 2.0) and the European Research Screening Prostate Cancer Risk Calculator 4 (ERSPC-RC 4). MATERIAL AND METHODS: Fifty-one patients underwent a prostate Bx according to standard clinical practice, with a minimum of 10 cores. The diagnosis of HGPC was agreed upon by 4 uropathologists. We compared the predictions from the various models by using the Mann-Whitney U test, area under the ROC curve (AUC) (DeLong test), probability density function (PDF), box plots and clinical utility curves. RESULTS: Forty-three percent of the patients had PC, and 23.5% had HGPC. The medians of probability for the 4KsT, PCPTRC 2.0 and ERSPC-RC 4 were significantly different between the patients with HGPC and those without HGPC (p≤.022) and were more differentiated in the case of 4KsT (51.5% for HGPC [25-75 percentile: 25-80.5%] vs. 16% [P 25-75: 8-26.5%] for non-HGPC; p=.002). All models presented AUCs above 0.7, with no significant differences between any of them and 4KsT (p≥.20). The PDF and box plots showed good discriminative ability, especially in the ERSPC-RC 4 and 4KsT models. The utility curves showed how a cutoff of 9% for 4KsT identified all cases of HGPC and provided a 22% savings in biopsies, which is similar to what occurs with the ERSPC-RC 4 models and a cutoff of 3%. CONCLUSIONS: The assessed predictive models offer good discriminative ability for HGPCs in Bx. The 4KsT is a good classification model as a whole, followed by ERSPC-RC 4 and PCPTRC 2.0. The clinical utility curves help suggest cutoff points for clinical decisions: 9% for 4KsT and 3% for ERSPC-RC 4. This preliminary study should be interpreted with caution due to its limited sample size.

[Are there any differences between the characteristics and the behavior of bladder cancer according to the age of presentation? Our experience]. / Existen diferencias en las caracteristicas y en el comportamiento del tumor vesical según edad de presentación? Nuestra experiencia.

INTRODUCTION: Owing to the different results from the series that evaluate the behavior of the bladder cancer according to the age at the moment of the diagnosis, our objective is based on valuing the characteristics and behaviour according to age of appearance. METHODS: A retrospective study of bladder cancer diagnosed in our area during decade 1993-2003, distributed in 3 intervals of age and some characteristics and behaviour are valued. RESULTS: Elderly patients present greater tumors, non differentiated and with greater rate of progression to infiltrated. Moreover the age, the pathological stage and the tumorlike degree appear as independent significant factors in the multivariant study. CONCLUSIONS: In our experience, the patients greater than 70 years present neoplasms of similar clinical characteristics, although pathologically more aggressive, with greater percentage of progression and worse survival.

[Steroid and xenobiotic receptor (SXR), multidrug resistance gene (MDR1) and GSTs, SULTs and CYP polymorphism expression in invasive bladder cancer, analysis of their expression and correlation with other prognostic factors]. / Expresion del receptor de esteroides y xenobioticos (SXR) y del gen de multirresistencia drogas (MDR1) y de los polimorfismos de las enzimas Gsts, SULTs y CYP en tumores vesicales profundos, analisis de su expresion y correlación con otros factores pronósticos.

INTRODUCTION: Steroid and Xenobiotic Receptor (SXR) has demonstrated its activation by numerous drugs, including cytochrome P450 potent inducers like rifampicina or cotrimazol. The role of SXR is well known, and lies regulating in a positive manner cytochrome P450 3A4 (CYP3A4) transcription and the multidrug resistance gene (MDR1), it's considered a key in the xenobiotic detoxification mechanism, being involved in all phases of the detoxification process. Enzymes involved in Policyclic Aromatic hidrocarbures (PAH) metabolism and degradation are polymorphic in humans, including glutation S-transferases (GSTs), N-acetiltransferases (NATs), sulfotransferases (SULTs)1A1 and cytochrome p450 (CYP)1B1. OBJECTIVES: The objectives we've planned are: 1. Analyze the expression of the transcription factor SXR and MDR1 in bladder by means of RT-PCR real time, both in normal bladder and in tumoral bladder. 2. Analyze the relation between clinical and pathological factors with the expression of SXR and MDR1. 3. Analyze the expression of the polymorphims CYP1B1, GSTM1 GSTT1 and SULT1A1 and their correlation with different clinic-pathological and molecular factors. MATERIAL AND METHODS: In a prospective way the size of the sample was estimated. In 67 patients from two institutions (Hospital Universitario Miguel Servet (49 HUMS) and Clinica Universitaria de Navarra (18 CUN)), diagnosed of invasive bladder cancer and treated by means of radical cystectomy, were determined the expression of both SXR and MDR1 by means of real time PCR, as well as the polymorphisms CYP1B1, GSTM1 GSTT1 y SULT1A1 by means of RFLP (Restriction fragment length polymorphism). Correlations with other prognostic factors by contingency tables were performed. RESULTS: Average follow up was 23.7 months with a median of 28.26 months. Of the 67 patients studied, 31 patients (46.3) presented disease progression, in form of local recurrence or in distant metastasis or both. With a average time to progression of 12.4 months and a median of 10 months, with a range of 1.1 month to 31.9 month. 36 patients (53.7%) did not have any evidence of disease progression during follow up. The Steroid and Xenobiotic Receptor as well as the Multidrug Resistance Gene (MDR1) are expressed in both normal bladder (0.94DeltaCt y 0.94DeltaCt) and tumoral bladder in the cystectomy specimen (1.09 DeltaCt y 0.45 DeltaCt). We've analyzed their expression in a quantitative manner and in a qualitative manner. The expression of SXR correlates with the presence of ca. in situ (p=0.024), vasculo-lymphatic invasion (p=0.05) mean while MDR1 correlates with presence of vasculo-lymphatic invasion (p=0.05) Both factors are correlate between each others (p=0.011). Polymorphisms: CYP1B1, GSTM1, GSTT1 and SULT1A1, are expressed in these patients but their expression doesn't correlates with any prognostic factor CONCLUSIONS: Both SXR and MDR1 are expressed in normal bladder as well as in tumoral bladder. And their expression correlates with different prognostic factors with influence in the survival described in the literature.

[Stage pT0 bladder tumors after radical cystectomy: a review of our series]. / Tumores de vejiga pT0 tras cistectomía radical: análisis de nuestra serie.

OBJECTIVES: To evaluate the data of progression and survival in 43 patients who underwent cystectomy with stage pT0 according to classification TNM-2002. MATERIALS AND METHODS: between 1988 and 2003 in our center had realized 420 cystectomies, 43 patients (10.2%) had not tumor in the cystectomy specimen. RESULTS: In these 43 cases the initial clinical stage (in the transuretral resection of bladder) was T1 in 10 cases (23,3 %), T2 in 31 cases (72%) and T3 in 2 cases. As far as the degree 24 patients presented G2 (55.8%) and 19 (44.2%) were G3. Median time from the transuretral resection to the cistectomy was of 44 days at a median follow-up of 89.3 months. Progression-free survival in the 43 patients was of 180,6 months, but during the follow-up it appeared progression in 7 patients, with disease free survival at 36 months (3-126), since the date of the cistectomia. During the follow up, 5 patients died. When we analyzed the cancer-specific survival according to tumor stage, for the T2 with an average cancer-specific survival is of 180 months, decreasing to 35 months considerably for T3. Similar it happens with the degree of differentiation, significantly diminishing as it advances the degree, with an average of cancer-specific survival for the G3 at 122.6 months. In the same way it happens with pathological positive lymph nodes in the radical cistectomy, with a cancer-specific survival of 188 months when it is N0 and of 54 months if the adenopathy was positive (N+). CONCLUSION: In our experiencie urothelial carcinoma pT0 present a prolonged free period of disease (medium of 180 months). The associated factors of risk to a smaller free period of disease are high degree of differentiation (G3, 116 months), the infiltration of deep layers in the transuretral resection (T3, 32 months) and the ganglionary affectation (pN+ 45 months).

[Primitive neuroectodermal tumor. Ewing's sarcoma]. / Tumor neuroectodérmico primitivo renal/sarcoma de Ewing.

Primitive neuroectodermal tumor is an extraordinarily rare primary tumor in the kidney and can be mistaken for a variety of other round cell tumors. It is important to recognize each of these entities, because each carries unique therapeutic and prognostic implications. However, accurate diagnosis of these tumors is hindered by their significant morphologic overlap and complicated by their rarity. These neplasm are highly aggressive that tend to recurence and to metastatize. Standard therapy combining surgery, chemotherapy, radiation and genetic therapy. We report a case of primitive neuroectodermal tumor of the kidney in a 50 year old female patient.

[Pseudotumor renal after partial nephrectomy with the use of surgical gelatin sponge]. / Pseudotumor renal tras el uso de materiales hemostáticos en la nefrectomía parcial.

After renal parenchymal sparing surgery, with the use of surgical gelatin sponge, residual defects may persist on imaging studies at the sites of resection. These "pseudotumors" may lead to confusion as to whether a lesion was removed or has recurred. These lesions usually resolve within a year. We report a case of pseudotumor renal parenchymal sparing surgery in a 69 year old man, with resolution of the lesion 8 months after surgery.

[Pelvic recurrence of urothelial tumor, after radical cysto-prostatectomy with orthotopic neo-bladder]. / Recidiva pélvica de tumor urotelial, tras cistoprostatectomía radical con neovejiga ortotópica.

We present a case of an urothelial tumor pelvic recurrence, five months after radical cystoprostatectomy. No fat infiltration was demonstrated in the pathological study of the transurethral resection pieces. The treatment was a radical cystoprostatectomy with an ileal ortothopic Hautmann type neo-bladder. The pathological study of the surgical piece demonstrated fat infiltration in some points but urethra and lymphatic nodes free.

[Skin metastasis of urothelial bladder tumor]. / Metástasis cutánea de tumor urotelial vesical.

We want to present a case of tranticional cell bladder carcinoma, where the first sign of disease progression was the appearance of a skin metastase. An unusual manifestation in a patient without another metastatic lesions.

[Prostatic rebiopsy. Prognosis factors of the anatomopathologic result]. / Rebiopsia de próstata. Factores pronósticos del resultado anatomopatológico.

The indications for repeat prostate needle biopsy after a previous biopsy are not defined. We examined 107 prostate biopsies (in 98 patients) without a diagnosis of malignancy, which we repeat. Carcinoma was detected in 31 patients (31.6%). We didn't find statistic relationship between the repeat biopsy's outcome and: interval between biopsy and repeat biopsy, PSA value, PSA density (biopsy), PSAD of the transitional area (PSAD ad., on repeat biopsy). We found relationship with: prostatic weight (p = 0.002 on the biopsy, p = 0.0002 on the repeat biopsy), volume of the transitional area (p = 0.02 on the biopsy, p = 0.0001 on the repeat biopsy), PSA value (p = 0.02, on the repeat biopsy), PSAD ad. (p = 0.002, on the repeat biopsy), and with PSA velocity (p = 0.008). We only found clinic usefulness for the PSA velocity: patients with PSA velocity greater than 1 ng/ml/year are at high risk for prostate carcinoma on the repeat biopsy, specially in small prostates.

[Stage pT3 prostatic cancer after radical prostatectomy. Results in progression and survival]. / Cáncer de próstata estadio pT3 tras prostatectomía radical. Resultados en progresión y supervivencia.

PURPOSE: To analyse progression and survival after radical prostatectomy in patients with stage pT3 carcinoma of the prostate. MATERIAL AND METHODS: Between 1986 and November 1998, we performed 372 radical prostatectomies, 74 of which were pT3N0 (19.8%), 43 pT3a and 31 pT3b (TNM 97). RESULTS: In patients with pathological stage pT3, we found any progression in 24 patients (32%), 8 in pT3a, and 16 in pT3b. In 10 of 24 pT3, there was local relapse or distant metastases. About the freedom from biochemical relapse survival rate, we found statistically differences between pT3a and pT3b (p < 0.0001). In pT3a patients, we found no differences between PSA levels > 20 ng/ml, versus < 20 (p = 0.415), and statistically differences between pathological Gleason 6 or greater, versus < 6 (p = 0.048). However, we found no differences when we used both criteria (PSA and Gleason) (p = 0.195). CONCLUSIONS: We support for early adjuvant hormonal therapy in pT3b patients. In pT3a, the hormonotherapy may be used if appears biochemical failure, specially with adverse prognostic factors (PSA and Gleason).

[The early diagnosis of prostate cancer in a selected population. The usefulness of PSAD, PSAD ad. and age-adjusted PSA in patients with a PSA between 4-10 ngr./ml]. / Diagnóstico precoz del cáncer de próstata en población seleccionada. Utilidad del PSAD, PSAD ad. Y PSA ajustado a la edad en pacientes con PSA entre 4-10 ngr./ml.

RATIONALE: Exposition of our experience in the early diagnosis of prostate cancer, based on the initial selection of patients. METHODS: Evaluation of patients from within the area covered by our hospital and seen for signs and symptoms of prostatism. Those with suspicion rectal examination (RE) or PSA greater than 4 ng/ml were further evaluated with transrectal ultrasound and prostate biopsy. RESULTS: Based on the biopsies of 700 patients, prostate carcinoma was diagnosed in 294/700 (42%). 55.72% patients with suspicion RE, and 47.5% with PSA > 4 had cancer. In patients with PSA > 4 and non-suspicion RE, cancer was detected in 16.44%. The percentage of neoplasia in patients with PSA 4-10 ng/ml and non-suspicion RE was 10%. As a result of these findings, 88 radical prostatectomies were performed. PASD and PASD ad. showed significant differences between patients with and without cancer, whether with (+)RE (p = 0.0001) or (-)RE (p < 0.0004), unlike PSA that showed no differences. The diagnostic value shown by PSAD ad. in ROC curves was similar to that of PSAD. Value of age-adjusted PSA was not higher than PSAD. CONCLUSION: Performance of prostate biopsy with a suspicion RE is recommended. If RE shows no suspicion, biopsy should be performed when PSA is > 10 ng/ml, and with PSA 4-10 ng/ml a biopsy is advocated with PSAD > 0.15.

[Unusual association of transitional cell carcinoma in the upper urinary tract, with contralateral renal metastasis and renal lithiasis of long clinical course]. / Infrecuente asociación de: carcinoma de células transicionales en T.U.S., con metástasis renales contralaterales y litiasis renal de larga evolución.

Presentation of a case reporting an infrequent association of transitional cell carcinoma of the upper urinary tract (UUT) with a long-standing renal polylithiasis and multifocal metastasis in contralateral kidney. A description is made of the incidence, etiology, prognostic factors as well as diagnosis and therapeutical approach.

[Analysis of a series of radical prostatectomies]. / Análisis de una serie de prostatectomías radicales.

OBJECTIVE: Radical prostatectomy (RP) is an elective therapeutical procedure for localized prostate cancer. The paper describes the critical analysis of our 10-year series. MATERIAL AND METHODS: A total of 216 RP have been performed between June 1986 and December 1996 (60 of them in the last year); with the purpose of securing a minimum follow-up of 4 months, the 204 procedures performed up to October 1996 were studied. Mean age was 64.9 years and PSA median 10.8 ng/ml. Intraglandular clinical stage was found in 192 cases versus 12 cases extraglandular. Up to the end of 1993 Walsh's technique with erectors' preservation was being used although the poor results obtained with regard to potency as well as the existence of positive borders have compelled us to perform the standard extracapsular technique since beginning of 1994. RESULTS: Mean follow-up in our series has been 29.62 months. Post-operative complications reached 29.9%, anastomosis fistula (21 cases) among the early ones and anastomosis stenosis (16 cases) among the late ones. 82.04% patients have total continence or minimal incontinence, the percentage of obstruction being 3.58%. Total impotence is estimated at 92.77%. One patient (0.49%) died in the immediate post-operative. Understaging was observed in 36.7%. 84 patients had extracapsular disease. Our percentage of positive surgical borders is of around 43.13%. Progression has been seen in 47 of 204 patients (23.03%): 8 local relapses, 12 metastasis, 3 with both conditions and 24 biological progression. Progression has been related to pathological stage, pre-operative PSA and Gleason's sum of the specimen. Difference was statistically significant. Overall survival at 1 and 5 years is 99.2% and 95.5% respectively while tumour specific survival is 97.8% and 75.8% at 1 and 5 years. CONCLUSIONS: RP is a surgery with minimal mortality but noticeable morbidity (incontinence 14.35%; impotence 92.77%; other complications from surgical technique 29.9%). Our clinical understaging is of around 36.7%. Progression is related to the specimen's pathological stage, and pre-operative PSA and Gleason. Our overall survival at 1 and 5 years is 99.2% and 95.5% respectively while tumour specific survival is 97.8% and 75.8%.

[Early diagnosis of cancer of the prostate. 5-year analysis]. / Diagnóstico precoz del cáncer de próstata. Análisis de cinco años.

The authors present the results obtained using a program for early diagnosis in symptomatic patients, within a specific population area. The effectiveness of this diagnosis program for prostate cancer, which is expected to be used also for diagnosis of less advanced stages, is established with the analysis of results obtained in 1000 patients: 42.5% positive biopsies. Biopsy indication in case of suspicious rectal examination and/or PSA over 10 ng/ml is considered useful. There are more reservations towards this indication with PSA values between 4 and 10 ng/ml, where evaluation of other complementary options is considered necessary.