Does a delay in initiating definitive therapy affect biochemical recurrence rates in men with clinically localized prostate cancer?

PURPOSE: To assess whether a delay in initiating definitive therapy for clinically localized prostate cancer affects outcome. METHODS: We retrospectively reviewed 393 men with localized prostate cancer treated with radiation therapy or surgery without systemic therapy between 1991 and 2004. Data included: time from diagnosis to treatment initiation (more or less than 3 months); biopsy Gleason score grouped by low (2-6), intermediate (7), or high risk (8-10); clinical stage grouped by low (T1/T2a) or high risk (T2b or higher); pretreatment prostate-specific antigen (PSA) grouped by low (<10 ng/ml), intermediate (10-20), or high risk (>20); and biochemical recurrence-free survival. RESULTS: Median patient age was 63.1 years (range 39.7-79.5). Median pretreatment PSA was 6.5 ng/ml (range 0.4-411). Median time from diagnosis to treatment was 57 days (range 8-2927). A total of 310 patients (79%) were treated within 3 months. Median follow-up was 2.3 years (range 0.1-14.0). On univariate analysis using Kaplan-Meier survival curves and the log-rank test, only pretreatment PSA was associated with worse biochemical recurrence-free survival (P = 0.008). Biochemical recurrence-free survival was not associated with time from diagnosis to treatment (P = 0.28), clinical stage (P = 0.50), or biopsy Gleason score (P = 0.19). The results were the same when analyzed in a multivariable analysis using the Cox proportional hazards model. CONCLUSION: A delay in treatment of > or =3 months does not appear to affect adversely biochemical recurrence-free survival in patients who undergo definitive therapy for clinically localized prostate cancer in those with low risk features.     

Are predictive models for cancer volume clinically useful in localized prostate cancer?

Objectives: To evaluate the correlation between preoperatively predicted and pathologically measured prostate cancer volumes and to investigate the clinical use of preoperatively predicted cancer volume in predicting pathological stage. Methods: Correlations between pathological findings and various preoperative parameters, including the cancer volumes as predicted by using two methods (Vca and estimated PCvol), were analyzed in 196 patients who underwent radical prostatectomy for clinically localized prostate cancer. Results: Pathologically measured prostate cancer volume was significantly correlated with the Vca and estimated PCvol, but the correlation coefficients were respectively only 0.46 and 0.35. Prostate‐specific antigen (PSA), PSA density (PSAD), primary Gleason score, Vca, Vca fraction (Vcafx), and estimated PCvol were significantly higher in 82 patients with extraprostatic cancer than in 114 patients with organ‐confined cancer. Magnetic resonance imaging (MRI) findings were significantly correlated with pathological stage. Multivariate logistic regression analysis indicated that the Vcafx and MRI findings were significant predictors of extraprostatic cancer, but receiver operating characteristic analysis revealed that the combination of Vcafx and MRI findings had no advantage over the combination of Gleason score, PSAD, and MRI findings. Conclusions: Vca and estimated PCvol are significantly correlated with the pathologically measured cancer volume but their ability to accurately predict cancer volume is limited. Vcafx and MRI findings were statistically significant predictors of extraprostatic cancer but their combination was not superior to the combination of Gleason score, PSAD, and MRI findings.     

Does the type of cryoprobe affect oncological and functional outcomes in men with clinically localized prostate cancer treated with primary whole gland prostate cryoablation?

Background:This study aimed to compare the oncological and functional outcomes of primary whole gland cryoablation of the prostate using the variable ice cryoprobe (V-Probe^®) and the conventional fixed-size ice probe.Materials and methods:We reviewed the Cryo On-Line Data Registry for men who were treated with primary whole gland prostate cryoablation from 2000 through 2017. A multivariate Cox proportional hazards model was used to compare timing to biochemical recurrence between the V-Probe^® and fixed-size ice probe after adjusting for preoperative prostate-specific antigen (PSA), neoadjuvant androgen deprivation therapy, preoperative Gleason score, and preoperative T stage.Results:A total of 1124 men were included. Median age, Gleason score, and pretreatment PSA were 70 years (interquartile range [IQR]: 65–74 years), 7 (IQR: 6–7) and 5.9 ng/mL (IQR: 4.6–8.1 ng/mL), respectively. The median follow-up time was 25.0 months (IQR: 11.2–48.6 months). V-Probes^® were used in 269 (23.9%) cases and fixed-size ice probes in 858 (76.1%) cases. After adjusting for clinical T stage, PSA, neoadjuvant androgen deprivation therapy and preoperative Gleason score, on the multivariate Cox regression model, we found that there was no significant difference between the type of probe and timing to biochemical recurrence (p = 0.35). On multivariate logistic regression, using the V-Probe^® was associated with a 91% increase in postoperative urinary retention compared to the fixed-size ice probe (p = 0.003).Conclusions:The use of the V-Probe^® versus conventional fixed-size ice probe was not associated with a difference in biochemical recurrence in patients undergoing primary cryoablation of the prostate.     

Does age influence the behaviour of localized prostate cancer?

OBJECTIVE: To assess, in a meta-analysis of published studies, whether age influences the behaviour of localized prostate cancer. METHODS: The Medline database was searched from 1966 to 2000 to identify studies analysing the outcome of localized prostate cancer by age, using disease-specific outcome measures, and having controlled for the established prognostic factors of grade, T stage and, where available, serum prostate-specific antigen (PSA) level. RESULTS: In all, 34 studies were identified, which included a total of 27 551 patients. The incomplete and heterogeneous nature of the reports precluded any quantitative overview. The findings of these reports are described and methodological shortcomings discussed. CONCLUSION: The evidence suggests that young age was an adverse prognostic factor in some series of radiation therapy before the advent of PSA assays, when men typically presented clinically with locally advanced disease, but that age has no significant prognostic effect in contemporary series of localized prostate cancer. Possible explanations for this difference are discussed, together with implications for further studies.     

Is tumor volume an independent prognostic factor in clinically localized prostate cancer?

PURPOSE: There continues to be debate regarding the prognostic significance of tumor volume (TV) in radical prostatectomy (RP) specimens. We assessed the prognostic significance of TV in a large series of patients followed for a long time to discover whether the effect of TV has changed with earlier detection of smaller tumors. MATERIALS AND METHODS: TV was measured planimetrically in 1,302 consecutive RP specimens with clinical stage T1-3 prostate cancer from 1983 to 2000. We correlated TV with standard clinical and pathological features, and determined the prostate specific antigen nonprogression rate. Median followup was 46 months (range 1 to 202). RESULTS: TV was weakly associated with other clinical and pathological features. Median TV decreased significantly over time (2.16 cm3 before 1995 vs 1.25 cm3 after 1995, p <0.001) and this decrease was also found within each clinical stage. In univariate analysis TV correlated strongly with the probability of progression. However, in multivariate analysis TV was not a significant independent predictor of prognosis, either in the whole cohort of patients or in those with peripheral zone cancer only. Even in univariate analysis TV had no effect on prognosis for patients in whom cancer was either confined to the prostate or was Gleason score 2 through 6. CONCLUSIONS: TV provides no independent prognostic information when considered in multivariate analysis with Gleason score and pathological stage. Measurement of TV before treatment is less likely to characterize prostate cancer accurately than assessment of tumor grade and extent. There seems to be little reason to measure TV routinely in RP specimens.     

Do prostate-specific antigen parameters have a similar role in predicting prostate cancer regardless of serum testosterone levels in men with gray-zone prostate-specific antigen levels?

BackgroundTo evaluate whether various prostate-specific antigen (PSA) parameters have a similar diagnostic value in predicting prostate cancer (PCa) in men with gray-zone PSA levels (4.0–10.0 ng/mL) depending on different serum testosterone levels.MethodsWe retrospectively reviewed the data of 635 men with gray-zone PSA levels who underwent prostate biopsy between January 2015 and December 2019. The study cohort was divided into two groups according to serum testosterone levels: normal (≥300 ng/dL) and low (<300 ng/dL) testosterone. Using the area under the receiver-operating characteristic curve (AUC), we analyzed the diagnostic accuracy of PSA parameters (total PSA, free PSA, free-to-total PSA ratio, testosterone-to-PSA ratio, and PSA density) in predicting PCa and compared the results between the two groups.ResultsThe median age was 68 (range, 40–88) years, and 76.1% (483 of 635) of the men had low testosterone levels. The PCa incidence was higher in the low testosterone group than in the normal testosterone group (45.5% vs. 35.5%, P=0.030). The AUC of free-to-total PSA ratio for predicting PCa showed no difference between the normal and low testosterone groups (AUC 0.616 vs. 0.684, P=0.257). Moreover, total PSA, testosterone-to-PSA ratio, and PSA density showed similar performance in predicting PCa between the two groups.ConclusionsThe analyzed PSA parameters showed a similar diagnostic value in predicting PCa regardless of testosterone levels in men with gray-zone PSA levels.     

Does body‐coil magnetic‐resonance imaging have a role in the preoperative staging of patients with clinically localized prostate cancer?

OBJECTIVE: To investigate the accuracy and use of body-coil magnetic resonance imaging (MRI) in the local staging of prostate cancer before radical prostatectomy (RP). PATIENTS AND METHODS: Fifty-six patients undergoing RP were staged before surgery using body-coil MRI; none was denied surgery on the basis of their scan results. All scans were reported before RP by one of three consultant radiologists and afterward by a colleague with a special interest in prostate MRI, unaware of the patients' clinical details. RESULTS: The overall sensitivity of MRI at detecting extracapsular extension was 50% on general reporting and 72% when reported by the specialist radiologist; the respective specificities were 84% and 86%. Of the 55 patients included in the study, 18 (33%) had extracapsular disease on histological analysis. MRI was most accurate in the 17 patients at high-risk (prostate-specific antigen, PSA, >10 ng/mL and Gleason score >or= 8) and eight at intermediate risk (PSA < 10 ng/mL and Gleason score 7). In the former group with specialist analysis, the sensitivity was 100%, although this decreased to 67% with general reporting. Both gave a specificity of 82%. Intermediate risk disease gave a sensitivity and specificity of 75%, irrespective of reporting method. The ability of MRI to detect extraprostatic tumour in the 30 low-risk patients (PSA < 10 ng/mL and Gleason score 2-6) was poor; the sensitivity was 25% with general and 50% on specialist review, although both methods gave a specificity of >90%. CONCLUSION: Body-coil MRI is sensitive and specific for identifying extracapsular extension of prostate cancer in patients with high- or intermediate-risk disease. Patients at low risk frequently have microscopic extension which is not detected. Opinion from a radiologist with a special interest in prostate MRI can increase the reporting accuracy even when unaware of the patients' clinical details.     

Is low serum free testosterone a marker for high grade prostate cancer?

PURPOSE: The association of free and total testosterone with prostate cancer is incompletely understood. We investigated the relationship of serum free and total testosterone to the clinical and pathological characteristics of prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the clinical records of 117 consecutive patients treated by 1 physician and diagnosed with prostate cancer at our medical center between 1994 and 1997. Low free and total testosterone levels were defined as 1.5 or less and 300 ng./dl., respectively. RESULTS: After evaluating all 117 patients we noted no correlation of free and total testosterone with prostate specific antigen, patient age, prostatic volume, percent of positive biopsies, biopsy Gleason score or clinical stage. However, in patients with low versus normal free testosterone there were an increased mean percent of biopsies that showed cancer (43% versus 22%, p = 0.013) and an increased incidence of a biopsy Gleason score of 8 or greater (7 of 64 versus 0 of 48, p = 0.025). Of the 117 patients 57 underwent radical retropubic prostatectomy. In those with low versus normal free testosterone an increased mean percent of biopsies demonstrated cancer (47% versus 28%, p = 0.018). Pathological evaluation revealed stage pT2ab, pT2c, pT3 and pT4 disease, respectively, in 31%, 64%, 8% and 0% of patients with low and in 40%, 40.6%, 12.5% and 6.2% in those with normal free testosterone (p>0.05). CONCLUSIONS: In our study patients with prostate cancer and low free testosterone had more extensive disease. In addition, all men with a biopsy Gleason score of 8 or greater had low serum free testosterone. This finding suggests that low serum free testosterone may be a marker for more aggressive disease.     

Androgen receptor expression in clinically localized prostate cancer： immunohistochemistry study and literature review

Aim： To evaluate androgen receptor （AR） expression in clinically localized prostate cancer （PCa）. Methods： Specimens were studied from 232 patients who underwent radical prostatectomy for clinically localized prostatic adenocarcinoma without neoadjuvant hormonal therapy or chemotherapy at our institution between November 2001 and June 2005. Immunohistochemical study was performed using an anti-human AR monoclonal antibody AR441. The mean AR density in the hot spots of different histological areas within the same sections were compared and the correlation of malignant epithelial AR density with clinicopathological parameters such as Gleason score, tumor, nodes and metastases （TNM） stage and pre-treatment prostate-specific antigen （PSA） value was assessed. Results： AR immunoreactivity was almost exclusively nuclear and was observed in tumor cells, non-neoplastic glandular epithelial cells and a proportion of peritumoral and interglandular stromal cells. Mean percentage of AR-positive epithelial cells was significantly higher in cancer tissues than that in normal prostate tissues （mean e SD, 90.0% ± 9.3% vs. 85.3% ±9.7%, P 〈 0.001）. The histological score yielded similar results. The percentage ofAR immunoreactive prostatic cancer nuclei and histological score were not correlated with existing parameters such as Gleason score, tumor, nodes and metastases stage and pre-treatment PSA value in this surgically treated cohort. Conclusion： The results of the present study suggest that there may be limited clinical use for determining AR expression （if evaluated in hot spots） in men with localized PCa.     

Studies on serum androgen changes in prostate cancer patients after castration

Aim: To observe the serum androgen changes in patients with prostate cancer (PCa) before and after castration. Methods: Serum testosterone (T), free testosterone (FT) and dihydrotest-osterone (DHT) were determined with radioimmunoassay in 16 cases with PCa one week before and on day 5 after castration. Results: After castration, the serum T, FT and DHT levels significantly declined by 92.27 %, 92.26 % and 58.36 %, respectively, as compared with the pre-castration values (P<0.01). Conclusion: After castration, most T and FT were deprived, while DHT only declined 58.36 %. Androgen receptor competitor should still be administered to antagnize the action of the remaining androgens.