[Consensus on castration-resistant prostate cancer management in Spain.] / Consenso sobre el manejo del cáncer de próstata resistente a la castración avanzado en España.

OBJECTIVES: To move towards a more standardized approach in clinical practice to manage patients with castration-resistant prostate cancer (CRPC) in Spain. METHODS: A panel of 18 Spanish experts in Urology with expertise managing CRPC followed a modified Delphi process with two rounds and a final face-to-face consensus meeting. The panel considered a total of 106 clinical questions divided into the following 6 sections: definition of CRPC, diagnosis of metastases by imaging techniques, symptoms of CRPC, progression of CRPC, M0 and M1 management and therapeutic sequencing. RESULTS: A bone scan (BS) is recommended at diagnosis, at the onset of bone pain, and depending on PSA levels, but it is not sensitive enough to confirm or exclude bone metastases if there is bone pain. Whole-body MRI and axial MRI are more sensitive than BS and plain X-rays, but more expensive, so they have to be used in certain situations. There is CRPC progression when there is radiologic, clinical or confirmed PSA progression. Flare phenomenon appears in treatment with taxanes and abiraterone. It was agreed that in M0 CRPC patients no drug treatment is currently recommended, although in M1 CRPC patients the first-line therapy would be mainly enzalutamide/abiraterone and/or docetaxel, depending on the symptom burden. CONCLUSION: After the consensus, we provide a series of recommendations for Spanish physicians treating CRPC to address the disease characteristics,how to tailor patient management decisions, the use of imaging techniques, and how to handle disease progression appropriately to improve patients' quality of life.

Consenso sobre el manejo del cáncer de próstata resistente a la castración avanzado en España / Consensus on castration-resistant prostate cancer management in Spain

OBJETIVOS: Establecer recomendaciones sobre la práctica clínica habitual del manejo del cáncer de próstata resistente a la castración (CPRC) en España. MÉTODOS: Un panel de 18 expertos en Urología con experiencia en el manejo del CPRC participaron en un proceso Delphi modificado a dos rondas con una reunión final presencial. El panel consideró un total de 106 cuestiones clínicas divididas en las siguientes secciones: definición del CPRC, diagnóstico de metástasis por técnicas de imagen, síntomatología, progresión, manejo de M0 y M1 y secuenciación terapéutica. RESULTADOS: Se recomienda realizar una gammagrafía ósea (GO) en el diagnóstico, al comienzo del dolor óseo y dependiendo de los niveles de PSA. La resonancia magnética de cuerpo entero y la axial son más sensibles que la GO y la radiografía, pero más caras, por lo que se reservan para ciertas situaciones. Existe progresión del CPRC cuando se confirma la progresión radiológica, clínica o por PSA. El fenómeno "flare" aparece en el tratamiento con taxanos y abiraterona. En pacientes M0 no se recomienda tratamiento farmacológico actualmente, y el tratamiento en primera línea para los pacientes M1 incluiría principalmente enzalutamida/ abiraterona y/o docetaxel, según los síntomas. CONCLUSIÓN: Se proponen recomendaciones para personalizar la toma de decisiones ante cada paciente, el uso de técnicas de imagen y cómo abordar la progresión de la enfermedad para mejorar la calidad de vida de los pacientes

OBJECTIVES: To move towards a more standardized approach in clinical practice to manage patients with castration-resistant prostate cancer (CRPC) in Spain. METHODS: A panel of 18 Spanish experts in Urology with expertise managing CRPC followed a modified Delphi process with two rounds and a final face-to-face consensus meeting. The panel considered a total of 106 clinical questions divided into the following 6 sections: definition of CRPC, diagnosis of metastases by imaging techniques, symptoms of CRPC, progression of CRPC, M0 and M1 management and therapeutic sequencing. RESULTS: A bone scan (BS) is recommended at diagnosis, at the onset of bone pain, and depending on PSA levels, but it is not sensitive enough to confirm or exclude bone metastases if there is bone pain. Whole-body MRI and axial MRI are more sensitive than BS and plain X-rays, but more expensive, so they have to be used in certain situations. There is CRPC progression when there is radiologic, clinical or confirmed PSA progression. Flare phenomenon appears in treatment with taxanes and abiraterone. It was agreed that in M0 CRPC patients no drug treatment is currently recommended, although in M1 CRPC patients the first-line therapy would be mainly enzalutamide/abiraterone and/or docetaxel, depending on the symptom burden. CONCLUSION: After the consensus, we provide a series of recommendations for Spanish physicians treating CRPC to address the disease characteristics how to tailor patient management decisions, the use of imaging techniques, and how to handle disease progression appropriately to improve patients' quality of life

Simplified technique for parastomal hernia repair after radical cystectomy and ileal conduit creation.

OBJECTIVE: To review the results of parastomal hernia repair with a simplified technique of translocation of the stoma with no need for a midline incision. METHODS: A total of 405 radical cystectomies with creation of an ileal conduit were reviewed at our institution. The primary goal of the review was to determine the incidence of parastomal hernias in a large series of cystectomies and their management at our institution. Surgical correction of parastomal hernia was indicated in case of pain, discomfort, risk of bowel obstruction, and/or distortion of the abdominal wall. The simplified technique includes an elliptical incision around the stoma and dissection of the hernia's sac down to the level of the fascia. The sac is incised and the peritoneum is entered. The ileal conduit is thereafter mobilized to guarantee sufficient length. This is crucial to be able to transpose the conduit 5-10 cm superiorly and to obtain a tension-free ileostomy. RESULTS: Sixty-three patients (16%) presented during the follow-up after ileal conduit a palpable defect or bulge adjacent to the stoma. The review highlighted 19 patients (4.69%) who developed a parastomal hernia and underwent surgical repair. Four cases (21%) recurred at a median follow-up of 55 months. Recurrence was not found to be related to gender, age, body mass index, protein level, radiotherapy, adjuvant chemotherapy, or previous abdominal surgery on univariate analysis. Postoperative complications included one wound infection (5.2%) and one stomal necrosis (5.2%). CONCLUSIONS: The technique herein proposed simplifies the management of parastomal hernia repair by avoiding a midline incision, which implies a reduction in surgical trauma with acceptable recurrence and postoperative complication rate.

Laparoscopic kidney transplantation.

We present the details of the first laparoscopic transplantation of a kidney from a living, related donor, performed April 16, 2009. Surgical and functional results were acceptable. Surgical time was 240 min (53 min for vascular suture), with blood loss of 300 cm(3) and a hospital stay of 14 d. Serum creatinine at discharge was 73 mmol/l. Laparoscopic kidney transplantation is a complex technique that requires previous experience in vascular and laparoscopic surgery. As with all novel procedures, technical modifications will be required to formalize its use and detailed comparisons will need to be made with standard procedures.

Case report: retroperitoneal fibrosis simulating local relapse of sarcomatoid renal cell carcinoma.

BACKGROUND: Generally, retroperitoneal fibrosis is an idiopathic process that envelopes and displaces ureters, causing hydronefrosis and renal failure. CT scan is the best choice for diagnosis. Other aetiologies described are malignancies, drugs, aorta aneurisms and immunological or rheumatological diseases. CASE PRESENTATION: A 53-year-old male with hypertension and diabetes was operated on radical nephrectomy for renal mass. Pathological examination showed sarcomatoid renal cell carcinoma, Fürhman 3 grade, pT2 N0. Within 6 months of surgery, control CT scan demonstrated a left retroperitoneal mass, without separation with pancreas queue and spleen hilium, suggesting local relapse. Resection of the mass with splenectomy and partial pancreatectomy en bloc was performed. Microscopic evaluation revealed a dense collagenic tissue with a prominent inflammatory infiltrate, and the immunohistochemical study was negative for cytokeratin AE1-AE3. There was no evidence of malignancy in the histological examination. All these findings aided to diagnose a retroperitoneal fibrosis. CONCLUSIONS: Sometimes retroperitoneal fibrosis can simulate or is associated to malignancies. Presentation of a retroperitoneal fibrosis simulating local relapse of sarcomatoid renal cell carcinoma has not been previously reported in the English literature.

Failure to maintain a suppressed level of serum testosterone during long-acting depot luteinizing hormone-releasing hormone agonist therapy in patients with advanced prostate cancer.

OBJECTIVES: It was the aim of this study to analyze the failure rates in achieving or maintaining castrate levels of serum testosterone in patients with advanced prostate cancer treated with the 3-month luteinizing hormone-releasing hormone agonist (LH-RH) therapy. METHODS: Total serum testosterone was determined in 234 patients with prostate cancer in a cross-sectional study. A subset of 90 patients submitted to radical prostatectomy was used as the control group (group 1), and 144 patients with advanced prostate cancer under androgen suppression therapy were included in the study group (groups 2 and 3). The study group was divided into 93 patients (group 2) treated with 50 mg daily bicalutamide and LH-RH agonist (maximal androgen blockade, MAB) and 51 patients treated with the LH-RH agonist alone (group 3). Median follow-up after androgen suppression was 42 months. The castrate testosterone level was defined below 50 ng/dl. RESULTS: The mean serum testosterone level was 29.1 ng/dl in patients undergoing MAB (group 2) and 29.5 ng/dl in patients treated with the LH-RH agonist (group 3; p > 0.05). In group 1, the mean serum testosterone was 445.2 ng/dl (p < 0.0001). The rate of patients with a serum testosterone level higher than 50 ng/dl was 10.9% in patients undergoing androgen suppression, 10% in patients with MAB treatment and 12.5% in those with LH-RH agonist therapy (p > 0.05). In group 1, 98.9% of the patients had a serum testosterone level higher than 50 ng/dl. CONCLUSIONS: A small but clinically significant rate of patients under 3-month LH-RH agonist therapy fail to achieve or maintain castrate testosterone serum levels. This finding supports the need of monitoring testicular response during LH-RH agonist therapy.

Effect of androgen deprivation therapy in the thyroid function test of patients with prostate cancer.

We have assessed the effect of androgen deprivation therapy (ADT) in the thyroid function test in prostate cancer patients. Serum levels of tri-iodothyronine (T3), thyroxine (T4), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were determined in a cross-sectional study that included 279 patients diagnosed with prostate cancer. A subset of 96 patients free of prostate-specific antigen relapse after radical prostatectomy became a control group and 183 patients under continuous ADT formed the study group. Sixty-four patients out of the study group were treated with luteinizing hormone-releasing hormone (LHRH) agonist and 119 with LHRH agonist plus bicalutamide. The average time of ADT was 42.5 months (3-218). Results were as follows. Mean T3 level was 122.7 ng/dl (72.6-213.0) in the control group and 123.8 ng/dl (64.4-228.2) in patients under ADT, p=0.472. Mean T4 level was 7.66 (1.81-4.30) and 7.66 microg/dl (3.60-13.30), respectively, p=0.884. Mean TSH level was 1.58 (0.44-11.70) and 1.81 mU/dl (0.15-6.58), respectively, p=0.007. Mean FT4 level was 1.24 (0.80-1.90) and 1.18 ng/dl (0.80-1.90), respectively, p=0.018. No statistically significant differences between the T3, T4, TSH and FT4 serum levels were detected according to the modality of ADT. The serum level of TSH was higher than 5 mU/l in six patients (2.1%); however, all cases had a normal FT4 serum level. This mild hypothyroidism was detected in two of the 96 patients of the control group (2.1%) and in four of the 183 under ADT (2.2%). Our data show that ADT seems to alter the thyroid function test. A statistically significant increase in TSH serum level and a decrease in FT4 serum level were detected in patients under ADT. However, only a mild hypothyroidism was detected in about 2% of the patients with prostate cancer, independently of ADT.

Nadir prostate-specific antigen best predicts the progression to androgen-independent prostate cancer.

The objective of our study was to analyze the value of prostate-specific antigen (PSA) levels before and after androgen suppression to predict the time to androgen-independent progression (AIP) in patients with advanced and metastatic prostate cancer. A series of 283 prostate cancer patients under androgen suppression as a single treatment was studied. The disease was locally advanced in 98 patients and metastatic in the remainder 185. AIP was defined after 2 consecutive increases of serum PSA after the nadir value. The mean follow-up before AIP was 29.2 months (3-198). AIP was detected in 205 patients (72.4%). In 152 patients (74.1%), the event was detected within 24 months, while in 53 patients (25.9%), it was observed beyond 24 months. The multivariate analysis showed that the nadir PSA and the time to reach the nadir PSA were the most significant predictors of the time to AIP. The odds ratio of having a biochemical response greater than 24 months was 20 times higher in patients that achieved an undetectable PSA level of 0.2 ng/mL or less. Moreover in those patients whose nadir PSA reached beyond 12 months after androgen suppression the odds ratio was 18 times higher. These results show that the ability to achieve an undetectable nadir PSA and the time to reach it are the most significant predictors of the time to AIP in patients with locally advanced and metastatic prostate cancer under androgen suppression as a single therapy.

The percentage of free prostatic-specific antigen is also useful in men with normal digital rectal examination and serum prostatic-specific antigen between 10.1 and 20 ng/ml.

OBJECTIVE: The percentage of free prostatic-specific antigen (PSA) has been introduced as a tool to avoid unnecessary biopsies in men with normal digital rectal examination (DRE) and serum PSA between 4.1 and 10 ng/ml. In this series we also analyze its utility in men with normal DRE and serum PSA between 10.1 and 20 ng/ml. MATERIALS AND METHODS: A series of 1149 consecutive men with normal DRE and serum PSA between 4.1 and 20 ng/ml submitted for the first ultrasound guided sextant biopsy is analyzed. In 921 (80.2%) the serum PSA was from 4.1 to 10 ng/ml and in 228 (19.8%) from 10.1 to 20 ng/ml. Total and free serum PSA determinations were done by the inmunoradiometric assays Tandem and Tandem free PSA (Hybritech Inc.). RESULTS: The overall detection rate of prostate cancer was 27.9%. In the group of men which serum PSA ranged from 4.1 to 10 ng/ml the rate of detection was 25.4% and 37.7% when it was between 10.1 and 20 ng/ml. Using 25% or less of percent free PSA as a criterion for performing prostatic biopsy it would have detected 95.3% and 95.4% of the prostate cancers, respectively. The rate of unnecessary avoided biopsies would be 17.5% when serum PSA ranged from 4.1 to 10 ng/ml and 17.6% between 10.1 and 20 ng/ml. CONCLUSIONS: This prospective study demonstrates that the percentage of free PSA seems to have similar utility when serum PSA levels are between 4.1 and 10 ng/ml and between 10.1 and 20 ng/ml, at the time of the first prostatic biopsy indication.

Increase of bone alkaline phosphatase after androgen deprivation therapy in patients with prostate cancer.

OBJECTIVES: To evaluate the behavior of bone alkaline phosphatase (BAP) after androgen deprivation therapy in patients with prostate cancer. METHODS: BAP was determined in the serum of 35 patients with nonmetastatic prostate cancer before maximal androgen blockade. During 5 years of follow-up, BAP was determined annually. A subset of 36 patients who underwent radical prostatectomy as the only treatment for prostate cancer was selected as a control group. RESULTS: The mean pretreatment BAP serum concentration was similar in both groups (10.8 and 10.4 ng/mL, P >0.05). However, after 5 years, the mean BAP serum concentration increased 64.8% in the study group (from 10.8 to 17.6 ng/mL, P < 0.001); it remained stable in the control group (from 10.4 to 10.4 ng/mL). The increase of serum BAP in patients receiving androgen deprivation was 32.4% during the first year (from 10.8 to 14.3 ng/ml), 16.7% during the second (from 14.3 to 16.1 ng/mL), 7.4% during the third (from 16.1 to 16.9 ng/mL), 5.5% during the fourth (from 16.9 to 17.3 ng/mL), and 2.8% during the fifth year (from 17.3 to 17.6 ng/mL). CONCLUSIONS: Androgen deprivation produces an increase in the BAP serum concentration. A major increase seems to be produced during the first year of follow-up and thereafter this increase is reduced around 50% annually.