Health-related quality of life in men with prostate cancer undergoing active surveillance versus radical prostatectomy, external-beam radiotherapy, prostate brachytherapy and reference population: a cross-sectional study.

BACKGROUND: The purpose of this study is to describe Health-Related Quality of Life (HRQoL) of localized prostate cancer patients in an Active Surveillance (AS) program, and to compare them with those undergoing radical prostatectomy (RP), external-beam radiotherapy (XRT) and brachytherapy (BT). METHODS: Multi-institutional pooled cross-sectional analysis on patients in an AS protocol: < 75 years old; pathologically confirmed LPC (maximum of three positive cylinders); Gleason score < 3 + 4; clinical stage T1a-T2b; and PSA < 15 ng/ml. Exclusion criteria for this study were: less than 6 months in AS, termination of AS protocol, or incomplete data. Patients in AS were matched with those treated with RP, XRT or BT from the 'Spanish Multicentric Study of Clinically Localized Prostate Cancer' cohort according to risk group, time from treatment selection to HRQoL survey, and age. Prostate-specific (EPIC) and generic (SF-36) HRQoL instruments were completed. Analysis was stratified by HRQoL survey moment (>or < 2.5 years from treatment selection), and age (>or < 70 years old). RESULTS: Median of time from treatment selection to HRQoL survey in the total 396 patients (99 per treatment group) was 2.4 years (range 0.5-8.3). Patients in AS presented higher (better) urinary incontinence scores than RP ones in both stratus of time from treatment selection to HRQoL survey (92.6 vs 67.0 and 81.4 vs 64.4, p <  0.01). Patients in AS for < 2.5 years presented greater sexual scores than any active treatment (p <  0.01), but only statistically higher than RP for those in AS for longer than 2.5 years. The magnitude of the differences between AS and RP groups in both EPIC domains ranged from moderate (0.7 SD) to large (1.0 SD). Regardless of treatment applied, patients presented similar and slightly increased SF-36 scores than US general population reference norms. Nonetheless, patients in AS for < 2.5 years reported worse outcomes than other treatment groups on physical health domains, especially in bodily pain (0.5-0.6 SD), and vitality (0.6-0.8 SD). CONCLUSIONS: Considering patients' well-being, AS can be a good therapeutic option due to the low impact caused on urinary continence and sexual function. However, longitudinal studies are required to take into account HRQoL evolution over time.

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)

[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.

Correlation between the biopsies in marginal donor kidneys for transplantation: is it necessary to biopsy both kidneys?

OBJECTIVES: The objective of this study was to analyze the correlation between histological findings in both transplanted kidneys from marginal donors. METHODS: We retrospectively reviewed the histological information on 92 kidneys obtained between January 2001 and January 2004, corresponding to 46 marginal donors. Criteria for biopsy were age greater than 55 years, hypertension, diabetes, and proteinuria. Scores were established by the pathologist including glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis. The score for each lesion was classified as 0 if absent; 1 if <20%; 2 if >20% and <50%; and 3 if >50%. Finally, we defined an index of renal severity damage (RSD) in order to classify the kidneys for single transplantation (0), double transplantation (1), and unsuitable for transplantation (2). RESULTS: Of the kidneys studied, 82.6% of both kidneys showed similar degrees of glomerulosclerosis (<20% in 71.7% and >20% in 10.9%), while 17.4% showed discrepancies (> vs <20%; P=.008). On the other hand, RSD correlated in 82.6% of both kidneys (in 69.6% RSD=0; in 8.7% RSD=1; and in 4.3% RSD=2), while 17.4% showed discrepancies (P=.001). In one case (2.2%), a great discrepancy was observed; one kidney was valid for single transplantation, and the other one not valid for any transplantation, single or double. CONCLUSIONS: This study demonstrated a correlation between the biopsy findings in both kidneys in 82.6% of marginal organ donors. However, in 17.4% of cases we observed discrepancies. The degree of glomerulosclerosis seemed to be a powerful parameter to define renal severity damage. According to these results we would recommend biopsy of both kidneys.

Behavior of free testosterone in patients with prostate cancer on androgen deprivation therapy.

OBJECTIVES: Determination of free testosterone (FT) serum level is an efficient method to evaluate bioavailable testosterone. We analyzed the behavior of serum FT in patients with prostate cancer receiving androgen deprivation therapy (ADT) and correlated FT with total testosterone (TT). We also analyzed the efficiency of both isoforms in the evaluation of the ADT. METHODS: Serum levels of TT and FT were determined in 191 patients with prostate cancer in a cross-sectional study. A subset of 56 patients submitted only to radical prostatectomy served as control group. The remaining 135 patients with advanced prostate cancer on three-month LHRH agonist treatment comprised the study group. The median age of the population was 73 years (range, 53-86 years) and the median time on ADT was 42 months (6-198). RESULTS: A significant correlation and linear regression between TT and FT was observed (r2 0.948). The efficiency of TT and FT to discriminate patients with and without ADT was similar (AUC: 0.993 and 0.995, respectively, p > 0.05). A castration level of serum FT established at 1.7 pg/mL had a sensitivity of 85.9% and a specificity of 100%, which are similar to the sensitivity and specificity of 50 ng/dL of TT. All patients without ADT had levels of serum TT and FT above the castration level. In 19 of the 135 (14.1%) patients on ADT serum TT was above 50 ng/dL. In 12 of these 19 patients (63.2%) serum FT was below 1.7 pg/mL while in seven patients (5.2%) FT was also above the castration level. CONCLUSIONS: The castration level of FT was established at 1.7 pg/mL. Serum TT and TF correlated very well; however, they seemed to provide complementary information in the evaluation of ADT efficiency. 14.1% of the patients on ADT failed to reach the castration level of serum TT; determination of serum FT in these patients would reduce this rate to 5.2%.

Usefulness of prostate-specific antigen nadir as predictor of androgen-independent progression of metastatic prostate cancer.

The objective of this study was to analyze the value of the nadir level of prostate-specific antigen (PSA) to predict androgen-independent progression (AIP) in metastatic prostate cancer patients after androgen deprivation therapy. In a group of 185 metastatic prostate cancer patients who received androgen deprivation therapy serum PSA was determined every three months until AIP occurred. Multiple regression analysis was performed to define independent clinical and PSA-related predictors of AIP. AIP was assumed to be present after two consecutive increases in serum PSA after the PSA nadir. Independent predictors of the duration of AIP-free survival (less than 12 months versus more than 12 months) were the extent of bone involvement (six or fewer hot spots versus more than six) with an odds ratio (O.R.) of 3.95, Gleason score (7 or less versus more than 7) with an O.R. of 3.47, and PSA nadir (2 microg/L or less versus more than 2 microg/L) with an O.R. of 14.63. AIP was independently predicted by the extent of bone involvement with an O.R. of 1.72, Gleason score with an O.R. of 1.74, PSA nadir with an O.R. of 3.22, and time to reach the PSA nadir (9 months or less versus more than 9 months) with an O.R. of 2.84. When patients were stratified according to these predictors, those with three good prognostic factors had a median AIP-free survival of 58 months while those with two, one or no good prognostic factors had a median AIP-free survival of 19 months, 12 months and 7 months, respectively. We conclude that the PSA nadir seems to be a good predictor of AIP in patients with metastatic prostate cancer after androgen deprivation therapy. Time to PSA nadir, extent of bone involvement and Gleason score are also independent predictors. The combination of these prognostic factors allows to stratify metastatic prostate cancer patients for the prediction of AIP.

Behavior of free testosterone in patients with prostate cancer on androgen deprivation therapy.

OBJECTIVES: Determination of free testosterone (FT) serum level is an efficient method to evaluate bioavailable testosterone. We analyzed the behavior of serum FT in patients with prostate cancer receiving androgen deprivation therapy (ADT) and correlated FT with total testosterone (TT). We also analyzed the efficiency of both isoforms in the evaluation of the ADT. METHODS: Serum levels of TT and FT were determined in 191 patients with prostate cancer in a cross-sectional study. A subset of 56 patients submitted only to radical prostatectomy served as control group. The remaining 135 patients with advanced prostate cancer on three-month LHRH agonist treatment comprised the study group. The median age of the population was 73 years (range, 53-86 years) and the median time on ADT was 42 months (6-198). RESULTS: A significant correlation and linear regression between TT and FT was observed (r2 0.948). The efficiency of TT and FT to discriminate patients with and without ADT was similar (AUC: 0.993 and 0.995, respectively, p>0.05). A castration level of serum FT established at 1.7 pg/mL had a sensitivity of 85.9% and a specificity of 100%, which are similar to the sensitivity and specificity of 50 ng/dL of TT. All patients without ADT had levels of serum TT and FT above the castration level. In 19 of the 135 (14.1%) patients on ADT serum TT was above 50 ng/dL. In 12 of these 19 patients (63.2%) serum FT was below 1.7 pg/mL while in seven patients (5.2%) FT was also above the castration level. CONCLUSIONS: The castration level of FT was established at 1.7 pg/mL. Serum TT and TF correlated very well; however, they seemed to provide complementary information in the evaluation of ADT efficiency. 14.1% of the patients on ADT failed to reach the castration level of serum TT; determination of serum FT in these patients would reduce this rate to 5.2%. (Int J Biol Markers 2005; 20: 119-22).

Osteoporosis during continuous androgen deprivation: influence of the modality and length of treatment.

OBJECTIVE: To analyze the prevalence of osteoporosis in patients with prostate cancer with and without androgen ablation. To know the influence of the modality and the length of androgen ablation on the prevalence of osteoporosis. To analyze the relative risk of hip fracture. MATERIAL AND METHODS: In a cross-sectional study, we assessed bone densitometry at the Ward's triangle of the femoral neck in 110 patients with non-metastatic prostate cancer and without biochemical relapse. A cohort of 53 patients under continuous androgen suppression during a median period of 41 months (12-191) formed the study group and 57 age-matched patients that had been submitted to a radical prostatectomy formed a control group. RESULTS: Both subsets of patients had similar mean age (70.4 vs. 69.2, p=0.07). Mean bone mass was 0.70 g/cm2 in patients under androgen suppression and 0.76 g/cm2 in the control group, p=0.06. The rate of osteoporosis was 41.5% (22/53) and 28.1% (16/57) respectively, p=0.16 and the odds ratio was 1.82 (95% CI 0,82-4.03). The rate of osteoporosis was 41.4% (12/29) in patients under maximal androgen blockade and 41.7% (10/24) in patients under chemical castration, p=0.735. According to the length of the androgen suppression the rate of osteoporosis was 36.4% when it was between 12 and 36 months, 42.1% from 36 to 60 months and 50% when it was longer than 60 months. While the overall relative risk of hip fracture in the control group was 2.0, it was 2.4 when the length of androgen suppression was between 12 and 36 months, 2.9 between 36 and 60 months and 3.9 when it was longer than 60 months. CONCLUSIONS: Androgen suppression increases the prevalence of osteoporosis in patients with prostate cancer. The modality of continues androgen suppression seems not to affect its prevalence. However the length of androgen suppression would be related to its development. The relative risk of hip fracture is also increasing during the androgen suppression.

Analysis of bone alkaline phosphatase as a marker for the diagnosis of osteoporosis in men under androgen ablation.

The objective of this study was to evaluate the usefulness of serum determination of bone alkaline phosphatase (BAP) in the diagnosis of osteoporosis in men with prostate cancer under androgen ablation. Serum levels of BAP and bone mineral density (BMD) were assessed in 110 patients with non-metastatic, treated prostate cancer. Fifty-eight patients were under androgen deprivation during a period between two and 96 months and 52 had been submitted only to radical prostatectomy. Mean serum BAP was 11.8 ng/mL in patients with normal BMD, 16.7 ng/mL in patients with osteopenia (p. 0.058), and 19.3 ng/mL in patients with osteoporosis (p = 0.044). The correlation between serum BAP and BMD was significant (p. 0.006) but with an index of only 0.26. Receiver operating characteristic analysis for the diagnosis of osteoporosis showed an area under the curve of 0.608. None of the cutoff points that provided specificities of 75%, 90% and 95% gave significant distributions. The positive and negative predictive values as well as the odds ratios were not of any clinical usefulness. We conclude that serum BAP should not be considered a good marker for the diagnosis of osteoporosis in men with prostate cancer. Therefore, BAP serum determination cannot replace bone densitometry as a diagnostic tool.

Value of percent free prostate-specific antigen for the prediction of pathological stage in men with clinically localized prostate cancer.

PURPOSE: To analyze if the percentage of free prostate-specific antigen (PSA) can provide additional information to the combination of local clinical stage, serum PSA and Gleason score in the prediction of final stage and pathological features of prostate cancer. MATERIALS AND METHODS: A group of 480 men with clinically localized prostate cancer underwent lymphadenectomy and radical prostatectomy. Total and free PSA were measured in preoperative serum. Clinical stage was T1 in 70.4% of patients and T2 in 29.6%. The biopsy Gleason score ranged between 2 and 4 in 5.6%, between 5 and 7 in 78.4%, and was higher than 7 in 16%. Total serum PSA was below 4.1 ng/mL in 4.3%, between 4.1 and 10 ng/mL in 66.4%, between 10.1 and 20 ng/mL in 22.5%, and higher than 20 in 6.7% of patients. The tumor was organ-confined in 49.8% and specimen-confined in 64.2%, and its pathological features were favorable in 35%. RESULTS: Multiple logistic regression analysis demonstrated that percent free PSA has independent predictive value for pathological stage only in the subset of patients with cT1 tumors and serum PSA between 4.1 and 10 ng/mL. In this group the probability of organ-confined cancer was 68.3% if the percent free PSA was above 15 and 56.3% if it was lower (p<0.001). The probability of specimen-confined disease was 86.6% and 71.3%, respectively (p<0.007), and the probability of favorable pathology was 59.8% and 39.6%, respectively (p<0.002). We also found higher rates of organ- and specimen-confined tumors and favorable pathology for every Gleason score when the percent free PSA was higher than 15. CONCLUSIONS: Percent free PSA seems to provide additional information to the combination of clinical stage and Gleason score for the prediction of pathological features only in patients with clinical stage T1c and serum PSA between 4.1 and 10 ng/mL.