Prostate-specific Antigen Drop Research Articles

Dual-Time-Point Posttherapy 177Lu-PSMA-617 SPECT/CT Describes the Uptake Kinetics of mCRPC Lesions and Prognosticates Patients' Outcome.

177Lu-PSMA-617 is an effective therapeutic option in metastasized castration-resistant prostate cancer (mCRPC). However, some patients progress under treatment. We hypothesized that the tracer kinetics within the metastases may influence the therapy effectiveness and tested this hypothesis by analyzing uptake parameters on 2 consecutive posttherapy SPECT/CT scans. Methods: mCRPC patients treated with 177Lu-PSMA-617 and with available posttherapy SPECT/CT imaging (24 and 48 h after the first treatment) were enrolled retrospectively. Volumes of interest were defined on lymph node metastasis (LNM) and bone metastasis (BM) on both SPECT/CT scans. The reduction of the percentage injected dose (%IDred) between the 2 SPECT/CT scans was computed. We compared %IDred of responders (prostate-specific antigen drop ≥ 50% after 2 cycles of 177Lu-PSMA-617) and nonresponders. We tested the association of %IDred with progression-free survival and overall survival (OS) using a univariate Kaplan-Meier (KM) analysis and a multivariate Cox regression model. Results: Fifty-five patients (median age, 73 y; range, 54-87 y) were included. %IDred in LNM and BM was greater in nonresponders than in responders (for LNM, 36% in nonresponders [interquartile range (IQR), 26%-47%] vs. 24% in responders [IQR, 12%-33%] [P = 0.003]; for BM, 35% in nonresponders [IQR, 27%-52%] vs. 18% in responders [IQR, 15%-29%] [P = 0.002]). For progression-free survival, in KM analysis, greater %IDred in LNM (P = 0.008) and BM (P = 0.001) was associated with shorter survival, whereas in multivariate analysis, only %IDred in LNM was retained (P = 0.03). In univariate KM analysis of OS, greater %IDred in BM was associated with shorter survival (P = 0.002). In multivariate OS analysis, BM %IDred (P = 0.009) was retained. Conclusion: The 177Lu-PSMA-617 clearance rate from mCRPC metastases appears to be a relevant prognosticator of response and survival, with faster clearing possibly signaling a shorter radiopharmaceutical residence time and absorbed dose. Dual-time-point analysis appears to be a feasible and readily available approach to estimate the likelihood of response and patients' survival.

Pulsed-wave vs Continuous-wave Thulium Fiber Laser Enucleation of the Prostate (ThuFLEP): A Comparison of Perioperative Outcomes

To compare intra and early postoperative outcomes between pulsed-wave and continuous-wave Thulium Fiber Laser Enucleation of the Prostate (PW-ThuFLEP vs CW-ThuFLEP) for the treatment of benign prostatic hyperplasia. 238 patients with lower urinary tract symptoms due to benign prostatic hyperplasia underwent PW-ThuFLEP (118 patients) vs CW-ThuFLEP (120 patients). Preoperative prostate volume, adenoma volume, prostate-specific antigen (PSA), and hemoglobin values were recorded. International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual volume, and International Index of Erectile Function-5 score (IIEF-5) were assessed. Operative time, enucleation time, enucleation efficiency, catheterization time, irrigation volume, hospital stay, hemoglobin drop, and postoperative complications were recorded. Micturition improvements and sexual outcomes were evaluated 3months after surgery. CW-ThuFLEP showed shorter operative time (61.5 vs 67.4minutes, P=.04). Enucleation time (50.2 vs 53.3minutes, P=.12), enucleation efficiency (0.8 vs 0.7g/min, P=.38), catheterization time (2.2 vs 2.1days, P=.29), irrigation volume (32.9 vs 32.8L, P=.71), hospital stay (2.8 vs 2.6days, P=.29) and hemoglobin drop (0.38 vs 0.39g/dL, P=.53) were comparable. No significant difference in complication rate was observed. At 3-month follow-up, the procedures did not show any significant difference in IPSS, Qmax, post-void residual volume, IIEF-5, and PSA value. PW-ThuFLEP and CW-ThuFLEP both relieve lower urinary tract symptoms equally, with high efficacy and safety. Operative time was significantly shorter with CW-ThuFLEP, but with a small difference with low clinical impact. Enucleation time, enucleation efficiency, catheterization time, irrigation volume, hospital stay, hemoglobin and PSA drop, complication rate, and sexual outcomes showed no differences.

MpMRI-US Fusion-Guided Targeted Cryotherapy in Patients with Primary Localized Prostate Cancer: A Prospective Analysis of Oncological and Functional Outcomes.

Simple SummaryTargeted cryotherapy is an emerging treatment for prostate cancer (PCa). mpMRI is a powerful tool for image fusion techniques that deliver incremental precision in diagnostic and treatment of PCa. Fusion targeted cryotherapy (FTC) arises from the simultaneous application of both these procedures. Recurrence is a concern after any type of PCa treatment, especially after targeted treatments. In this article we investigate the recurrence rate after FTC and the role of Prostate-Specific Antigen (PSA) as a predictor of recurrences. Our research provides new evidence on the feasibility of FCT by providing new insights on patient management.Targeted therapy (TT) for prostate cancer (PCa) aims to ablate the malignant lesion with an adequate margin of safety in order to obtain similar oncological outcomes, but with less toxicity than radical treatments. The main aim of this study was to evaluate the recurrence rate (RR) in patients with primary localized PCa undergoing mpMRI/US fusion targeted cryotherapy (FTC). A secondary objective was to evaluate prostate-specific antigen (PSA) as a predictor of recurrences. We designed a prospective single-center single-cohort study. Patients with primary localized PCa, mono or multifocal lesions, PSA ≤ 15 ng/mL, and a Gleason score (GS) ≤ 4 + 3 undergoing FTC were enrolled. RR was chosen as the primary outcome. Recurrence was defined as the presence of clinically significant prostate cancer in the treated areas. PSA values measured at different times were tested as predictors of recurrence. Continuous variables were assessed with the Bayesian t-test and categorical assessments with the chix-squared test. Univariate and logistic regression assessment were used for predictions. A total of 75 cases were included in the study. Ten subjects developed a recurrence (RR: 15.2%), while fifty-six (84.8%) patients showed a recurrence-free status. A %PSA drop of 31.5% during the first 12 months after treatment predicted a recurrence with a sensitivity of 53.8% and a specificity of 79.2%. A PSA drop of 55.3% 12 months after treatment predicted a recurrence with a sensitivity of 91.7% and a specificity of 51.9%. FTC for primary localized PCa seems to be associated with a low but not negligible percentage of recurrences. Serum PSA levels may have a role indicating RR.

PRIMERA trial (NCT04188275), early survival results from a prospective trial exploring impact of circulating tumor cell detection in castrate resistant prostate cancer patients undergoing abiraterone or enzalutamide I line treatment.

137 Background: Circulating tumor cells (CTC) detection and androgen receptor splice variant 7 (ARV7) expression have been shown to be associated with worse clinical outcomes in metastatic castration resistant prostate cancer (mCRPC) patients undergoing androgen receptor targeted agents (ARTA) treatment, paving the way for alternative treatment options for patients with negative predictive factors. Full-length androgen receptor (ARFL), prostate specific membrane antigen and prostate specific antigen (PSA) may further help to refine prognostic models. In our institution, a prospective observational trial testing CTC detection in mCRPC undergoing ARTA treatment (PRIMERA trial, NCT04188275) terminated the planned enrollment in 2020. Here we present early results of the overall cohort. Methods: PRIMERA (NCT04188275) is a prospective, observational trial enrolling mCRPC patients undergoing ARTA treatment. All patients were treated with either abiraterone or enzalutamide in I line setting. Blood samples to detect CTCs were taken before starting ARTA treatment. Reverse transcription - quantitative real-time PCR (RT-qPCR) was used to determine the CTC expression of PSA, PSMA, AR and ARV7. PSA drop (defined as difference between baseline PSA at ARTA treatment start and PSA at nadir under treatment), progression free and overall survival (PFS and OS) and their correlation with CTC detection were reported. Explorative analysis about AR, PSA and PSMA expression in CTC+ patients were conducted. Results: Overall, 44 patients were included. CTC were detected at treatment start in 19 patients (43,2%), of whom 3(15,78%), 9(63,15%), 15(78,94%) and 14 (73.68%) patients expressed ARV7, ARFL, PSA and PSMA, respectively. Biochemical response was significantly improved in CTC+ vs. CTC- patients, with median PSA drop values of 18.5 vs 2.5 ng/ml (p=0.03). After a median follow up of 18 months, 22 (50%) patients progressed. PFS was significantly longer in CTC- patients (not reached vs 16 months, respectively, p=0.02). Eight (18.2%) patients died, a non-significant trend in terms of overall survival was detected in favor of CTC- patients (not reached vs 29 months, respectively, p=0.05). AR, PSA and PSMA expression in CTC+ had no significant impact on PSA drop, PFS or OS. Conclusions: PRIMERA trial confirmed the CTC detection predictive importance in mCRPC patients. Adequately powered studies will be needed to further explore CTC profiling in this setting. Clinical trial information: NCT04188275.

Castration failure in prostate carcinoma due to a functioning adrenocortical carcinoma.

SummaryWe report concurrent metastatic prostatic adenocarcinoma (PC) and functioning androgen-secreting adrenocortical carcinoma (ACC) in a 77-year-old man. The failure to achieve adequate biochemical castration via androgen deprivation therapy (ADT) as treatment for PC metastases, together with elevated DHEA-S, androstenedione, and discordant adrenal tracer uptake on FDG-PET and PSMA-PET, suggested the presence of a concurrent functional primary adrenal malignancy. On histopathological analysis, scant foci of PC were present throughout the ACC specimen. Castration was achieved post adrenalectomy with concurrent drop in prostate-specific antigen. We outline the literature regarding failure of testosterone suppression on ADT and salient points regarding diagnostic workup of functioning adrenal malignancies.Learning pointsFailure to achieve castration with androgen deprivation therapy is rare and should prompt careful review to identify the underlying cause.All adrenal lesions should be evaluated for hormone production, as well as assessed for risk of malignancy (either primary or secondary).Adrenocortical carcinomas are commonly functional, and can secrete steroid hormones or their precursors (androgens, progestogens, glucocorticoids and mineralocorticoids).In this case, a co-incident, androgen-producing adrenocortical carcinoma was the cause of failure of testosterone suppression from androgen deprivation therapy as treatment for metastatic prostate cancer. Pathological adrenal androgen production contributed to the progression of prostate cancer.

Changing Paradigms: Green Laser Vaporization for Prostates over 80 mL: A Comparative Study.

Introduction and Objectives: Benign prostatic enlargement (BPE) and big prostates are common. Photovaporization of the prostate (PVP) with Greenlight™ laser 180 W XPS is considered a reliable therapy for prostates <80 mL and an alternative for the treatment of bigger ones in selected cases. The aim of this study is to evaluate efficacy, safety, and functional outcomes of PVP among patients with prostates over and under 80 mL. Materials and Methods: After protocol approbation by our Institutional Ethics Committee, a cohort of 840 patients with BPE who underwent PVP with Greenlight laser between 2012 and 2019 in a single center was evaluated. Groups were stratified according to prostate volume, to less and greater than 80 mL (Groups 1 and 2, respectively). The primary outcomes were efficacy [prostate-specific antigen (PSA) drop, improvement of International Prostatic Symptom Score (IPSS), and quality of life] and variables regarding safety of the procedure. Peri- and postoperative outcomes were analyzed. Complications were assessed according to Clavien-Dindo classification. Overall patient satisfaction was evaluated with visual analog scale. Results: Preoperative variables showed no statistical difference among groups. Mean follow-up was 47 [interquartile range; IQR = 26-70] months. Longer operative time and a higher energy use was seen in bigger prostates (p < 0.001). Efficacy was similar between groups, with a reduction of ≥4 points in IPSS score in 83.1% and 89.5% in Groups 1 and 2 (p = 0.053), PSA drop was 1 ± 2.6 and 1.7 ± 4.7 (p = 0.32). Group 2 had a higher conversion rate (0.3% vs 4.9%, p < 0.001) and higher blood transfusion rate (0% vs 2.4%, p < 0.001). There were no differences in hospital stay, catheterization time, urethral stricture, or re-treatment rates. Conclusions: GreenLight PVP is a safe and effective procedure in prostates ≥80 mL. It shows the same advantages demonstrated for those under that volume, particularly short hospital stay and catheterization time. Surgeon's experience is important to avoid complications, such as conversion and transfusion. PVP should be considered a first-line alternative for the treatment of bigger prostates.

Interim Prostate-Specific Antigen: Predicting for Biochemical Failure During Salvage Radiation Therapy After Prostatectomy

PurposeA subset of patients treated with postprostatectomy radiation therapy for biochemical recurrence after surgery fail to respond because of microscopic disease beyond the irradiated prostate bed. This work aims to determine whether a rising interim prostate-specific antigen (PSA) during radiation therapy can predict the likelihood of subsequent biochemical recurrence. Methods and MaterialsBetween 2010 and 2016, 185 patients had salvage radiation therapy to a dose of 68 Gy without androgen deprivation therapy for a rising PSA level after radical prostatectomy. Patients had their PSA recorded on the first day of radiation therapy and again after completing the 25th fraction (of 34 total fractions). Biochemical failure after radiation therapy was defined as a PSA value ≥0.2 ng/mL within 2 years after radiation therapy. Both univariate and multivariate Cox regression models were used for statistical analysis. Factors with a P value of <.2 in univariate analysis were then used in a multivariate analysis. ResultsThe 2-year freedom from biochemical failure was 60% (95% confidence interval, 53%-67%). When assessing the interim PSA, 143 patients (77%) had a drop in interim PSA; of these patients, 71% had 2-year biochemical control. Forty-two patients (23%) had a stable or rising interim PSA, and only 24% of these patients had 2-year biochemical control. On multivariate analysis, a drop in PSA during radiation therapy (P < .0001) and a positive surgical margin (P < .0001) were significant factors for freedom from subsequent biochemical failure, and seminal vesicle invasion was associated with biochemical failure at 2 years (P = .019). All patients with a rising interim PSA, negative surgical margin, and seminal vesicle invasion ultimately had biochemical failure at 2 years. ConclusionsA PSA rise during salvage radiation therapy is prognostic of biochemical failure at 2 years. Factors such as seminal vesicle invasion and a negative surgical margin also predict for poor responders to salvage radiation therapy.

Factors associated with response to Androgen Deprivation Therapy in patients with Metastatic Prostate Cancer at the University Teaching Hospital Lusaka, Zambia

Background: Prostate cancer in most cases is dependent on the presence of androgens (testosterone) produced either by the testis or adrenal gland. The major risk factors for development include aging, ethnicity and genetic predisposition. Organ confined prostate cancer is curable by surgery or radiotherapy while metastatic disease is treated by androgen deprivation therapy (ADT). ADT can be achieved medically (gonadotropin releasing hormone agonists or antagonists) or surgically (bilateral orchiectomy). A decrease in serum prostate specific antigen (PSA) is used as a marker of response to ADT. Metastatic prostate cancer has been found to be the most common cause of death in the urology department at the University Teaching Hospitals – Adult Hospital even after ADT, therefore, the aim of this study was to identify the pre-treatment factors that can be used to determine the response to ADT.&#x0D; Methodology: This was a cross section study conducted at the University Teaching Hospitals- Adult Hospital and Cancer Diseases Hospital. It was carried out between December 2017 and September 2018. Patients with metastatic prostate cancer were recruited. Socio-demographic characteristics, clinical presentation and histopathological findings were elicited by detailed history and file review. PSA and Eastern Cooperative Oncology Group (ECOG) performance status score were obtained prior to ADT commencement. ADT was done and patients were scheduled for a three month post ADT review where PSA and ECOG performance status score were reobtained.&#x0D; Results: 50 patients were recruited into the study. The total patient retention was 88% (n=44). The average age was 71. Majority, 89% (n=39) had some level of education; 98% (n=43) had lower urinary tract symptoms (LUTS); 11% (n=5) had paraplegia. 98% (n=43) had bone metastasis. Duration of symptoms at presentation was &gt; 6 months in 75% (n=33) patients. ECOG score was above 1 in 75% (n=33). Initial PSA was above 100ng/ml in 75% (n=38). All patients had Gleason scores above 7. All patients had a drop in PSA after ADT. The average PSA percentage drop in men below 60 years was 80.5% whereas the average percentage drop in PSA with regards to other factors was 91.19%.&#x0D; Conclusion: All patients had androgen dependant cancers. These patients also had high risk prostate cancer with initial PSA values above 100ng/ml and Gleason scores above 7. Of all the factors analysed, age below 60 years was found to be the only clinically significant factor associated with poor response to ADT.

Prognostic role of early PSA drop in castration resistant prostate cancer patients treated with abiraterone acetate or enzalutamide.

Previous studies demonstrated a predictive value of prostate-specific antigen (PSA) kinetics for treatment outcome. Our retrospective study evaluates the prognostic role of early PSA drop in metastatic castration resistant prostate cancer (mCRPC) patients receiving abiraterone acetate (AA) or enzalutamide (E). All mCRPC patients treated with AA or E at the San Luigi Hospital in Orbassano between 2010 and 2018 and at the Ordine Mauriziano Hospital in Turin between 2014 and 2018 were included in this retrospective study. Only patients with an early PSA (measured 28-60 days after the beginning of the treatment) were included in the analysis. Patients were divided in early responders and non-early responders according to early PSA response (drop≥50% from baseline). Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were performed. Of 144 patients with early PSA value, 61 (42.4%) patients received E (docetaxel-naïve 42, post-docetaxel 19) and 83 (57.6%) received AA (docetaxel-naïve 44, post-docetaxel 39). Seventy-five (52.1%) patients achieved early PSA drop. In docetaxel-naïve setting (N.=86), median PFS was 14.9 (with early PSA drop) vs. 8.8 months (without early PSA drop, P=0.001). In post-docetaxel setting (N.=58) median PFS was 11.9 vs. 4.5 months (P<0.001). Globally, median PFS was 14.9 vs. 6.3 months in patients with and without early PSA drop, respectively (P<0.001). In docetaxel-naïve setting, patients with early PSA drop had a median OS of 39.5 vs. 18.8 months (P=0.12). In post-docetaxel setting median OS was 29.6 vs. 10.7 months (P=0.01). Comprehensively, median OS was 31.9 vs. 16.3 (P=0.002) in patients with and without early PSA drop, respectively. At multivariate analysis, early PSA drop confirmed an independent association with PFS (HR 0.21; 95% CI: 0.12-0.38, P<0.001) and OS (HR 0.25; 95% CI: 0.12-0.50, P<0.001). mCRPC patients treated with AA or E, in docetaxel-naïve or post-docetaxel setting, with early PSA drop had significantly better OS and PFS.

Factors associated with response to Androgen Deprivation Therapy in patients with Metastatic Prostate Cancer at the University Teaching Hospital Lusaka, Zambia

Background: Prostate cancer in most cases is dependent on the presence of androgens (testosterone) produced either by the testis or adrenal gland. The major risk factors for development include aging, ethnicity and genetic predisposition. Organ confined prostate cancer is curable by surgery or radiotherapy while metastatic disease is treated by androgen deprivation therapy (ADT). ADT can be achieved medically (gonadotropin releasing hormone agonists or antagonists) or surgically (bilateral orchiectomy). A decrease in serum prostate specific antigen (PSA) is used as a marker of response to ADT. Metastatic prostate cancer has been found to be the most common cause of death in the urology department at the University Teaching Hospitals – Adult Hospital even after ADT, therefore, the aim of this study was to identify the pre-treatment factors that can be used to determine the response to ADT.&#x0D; Methodology: This was a cross section study conducted at the University Teaching Hospitals- Adult Hospital and Cancer Diseases Hospital. It was carried out between December 2017 and September 2018. Patients with metastatic prostate cancer were recruited. Socio-demographic characteristics, clinical presentation and histopathological findings were elicited by detailed history and file review. PSA and Eastern Cooperative Oncology Group (ECOG) performance status score were obtained prior to ADT commencement. ADT was done and patients were scheduled for a three month post ADT review where PSA and ECOG performance status score were reobtained.&#x0D; Results: 50 patients were recruited into the study. The total patient retention was 88% (n=44). The average age was 71. Majority, 89% (n=39) had some level of education; 98% (n=43) had lower urinary tract symptoms (LUTS); 11% (n=5) had paraplegia. 98% (n=43) had bone metastasis. Duration of symptoms at presentation was &gt; 6 months in 75% (n=33) patients. ECOG score was above 1 in 75% (n=33). Initial PSA was above 100ng/ml in 75% (n=38). All patients had Gleason scores above 7. All patients had a drop in PSA after ADT. The average PSA percentage drop in men below 60 years was 80.5% whereas the average percentage drop in PSA with regards to other factors was 91.19%.&#x0D; Conclusion: All patients had androgen dependant cancers. These patients also had high risk prostate cancer with initial PSA values above 100ng/ml and Gleason scores above 7. Of all the factors analysed, age below 60 years was found to be the only clinically significant factor associated with poor response to ADT.

Safety Profile and Therapeutic Efficacy of One Cycle of Lu177-PSMA in End-Stage Metastatic Castration-Resistant Prostate Cancer Patients with Low Performance Status.

The aim of this study was to evaluate safety and therapeutic efficacy of lutetium 177 prostate-specific membrane antigen (Lu-177-PSMA) in metastatic castration-resistant prostate cancer (mCRPC) patients with low performance status. Twenty-two patients already treated with anti-androgens and docetaxel were enrolled for one cycle of Lu-177-PSMA therapy. Haemoglobin, total leukocyte counts, platelets and serum creatinine for toxicity profile while prostate specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, visual analogue scale (VAS) and analgesic quantification scale (AQS) for therapeutic efficacy were recorded pre and 8weeks post therapy. Wilcoxon signed-rank and ANOVA tests were used for statistical analysis. Partial response (PR), stable disease (SD) and progressive disease (PD) for PSA were seen in 5 (22.7%), 13 (59.1%) and 4 (18.2%) patients respectively treated with mean 6.88GBq dose of Lu-177-PSMA. 8/22 (36.4%) patients showed ≥ 30% drop in PSA. Grade 3 haemoglobin toxicity was seen in 5/22 (22.7%) patients. No patient developed grade 4 haemoglobin toxicity. No patients had grade 3 or 4 leukocytopenia or thrombocytopenia. Wilcoxon signed-rank test showed statistical significant (P < 0.05) difference in pre and post treatment ECOG, VAS, and AQS scores. The ANOVA test showed statistically significant difference in mean doses of Lu-177-PSMA used in three PSA response groups while difference was non-significant for other variables. We concluded that Lu-177-PSMA therapy has adequate pain palliation in end-stage mCRPC patients with low performance status and it has a potential to become effective therapeutic option in properly selected patients.

The impact of diurnal variation of PSA on timing of measurement in prostate biopsy.

Prostate-specific antigen (PSA) synthesis is related to testosterone, which has a diurnal rhythm. PSA might have a diurnal variation and the timing of measurement could change the clinical practice for prostate biopsy. Male patients complaining of lower urinary tract symptoms (group 1) and diagnosed with prostate cancer (group 2) were recruited into the study. Morning fasting blood samples were withdrawn between 9.00 and 11.00 am for the determination of biochemical parameters, PSA (PSA1), total testosterone (T1), and estradiol (E1) levels. In the afternoon, between 15.00 and 15.30 pm, blood samples were again obtained from the same participants at the same day and the serum concentration of PSA (PSA2), total testosterone (T2), and estradiol (E2) were measured. A total of 160 and 30 patients were enrolled in groups 1 and 2, respectively. One hundred forty (87.5%) and 26 (86.6%) patients had a decrease in the PSA levels when measured in the afternoon. The Wilcoxon signed-rank test determined a statistically significant difference between the PSA levels measured in the morning and in the afternoon in each group. An analysis of covariance test revealed no statistically significant difference in PSA concentration between the groups after adjustment for baseline concentration (F(1.187) = 0.203, P = .653). There was a weak positive correlation between PSA1/PSA2 and T1/T2, rs (160) = 0.163, P = .034. An extra unit increase in PSA1 concentration leads to a 0.805 (95% confidence interval [CI], 0.781-0.830) and 0.828 (95% CI, 0.807-0.849) ng/mL increase in PSA2 concentration in groups 1 and 2, respectively, that is, patients with and without prostate cancer had a similar decrease in the PSA levels. When measured in the afternoon, 66.6% and 50% patients with a morning PSA level over 3 or 4 ng/mL had a PSA drop below these levels, respectively. PSA has a diurnal variation and the timing of measurement may alter the decision of the clinician for transrectal ultrasound prostate biopsy.

Diethylstilbestrol in the Treatment of Castration-resistant Prostate Cancer: A Lower-middle-income Country Experience.

Introduction: Prostate cancer is the second most common cancer and the fifth leading cause of death worldwide. Its metastatic stage is associated with considerable morbidity and may lead to death. In Pakistan, given the high levels of economic constraint, patients with castration-resistant metastatic prostate cancer can be treated with cost-effective medications like diethylstilbestrol (DES).Objectives: The goal of this study was to assess the efficacy and adverse effects of DES when used in patients with castration-resistant prostate cancer (CRPC).Materials and methods: From January 2011 to December 2016, all medical records of patients with a diagnosis of prostate cancer resistant to the effects of castration presenting at Shaukat Khanum Cancer Hospital and Research Centre, Lahore, were reviewed. All patients were treated with DES (2.5 mg) initially, but the dose was increased for some patients to 5 mg in combination with aspirin (75 mg). The patients were followed clinically with prostate-specific antigen (PSA) value assessment. The PSA response to treatment, time to disease progression, and adverse events were recorded and analyzed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY).Results: A total of 91 patients were included in the study, and the mean patient age was 66 ± 8 years. The median baseline PSA was 150 ng/mL (range: 56-626 ng/mL), and the median Gleason’s score was eight. A total of 90.1% of patients had metastatic disease at the time of diagnosis. Hormonal ablation was provided with bilateral orchiectomy for 71 patients (78.0%), and luteinizing hormone-releasing hormone (LHRH) analog was provided for 20 patients (22.0%). With this treatment, the median time to PSA progression was 597 days. After DES treatment was started, 78 patients (87.7%) showed a PSA response, and median time to progression was 212 days. In 24 patients (26.4%), the PSA response was maintained for more than a year. The PSA response was quantified as a good response (i.e., ≥50% PSA drop) or as a partial response (i.e., <50% PSA drop). The good PSA response was observed in 56 patients (61.5%) with a median time to progression of 273 days, and 22 patients (24.2%) had a partial response maintained for 109 days. Thirteen patients (14.3%) did not respond to DES treatment. The median percent change in PSA was -55.52% (range: -99.9 to +422). Thromboembolic complication was observed in eight patients (8.7%) patients while two patients suffered from liver toxicity.Conclusion: DES is an effective, economical, and relatively safe drug in patients with CRPC.

Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer

In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging. To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial. In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard. Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety. A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P < .001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients. Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer. ClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.

PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients.

We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients. This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR. A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48-82) years and 19 (6.3-38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p=0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04ng/ml/month, p=0.001). Similar to PSAV (HR 9.570, 95% CI 3.725-24.592, p<0.0001), PSA nadir≥2ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100-1.422, p=0.001] was independently associated with BCR. A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.

Thulium laser enucleation of the prostate is a safe and a highly effective modality for the treatment of benign prostatic hyperplasia - Our experience of 236 patients

Context:Thulium LASER is fast emerging as a safe and effective modality for benign prostatic hyperplasia (BPH). Still, compared to holmium laser transurethral enucleation of the prostate (HoLEP) the number of institutes all over the world using Thulium LASER are limited. This is our effort to bring the statistical facts about the safety and effectivity of Thulium LASER.Aims:To study the efficacy of thulium laser enucleation of the prostate (ThuLEP).Settings and Design:All patients in the stipulated period were documented for all parameters and were evaluated. The results were tabulated.Subjects and Materials:(1) Two hundred and thirty-six patients with symptomatic BPH were treated with ThuLEP between March 2010 and September 2014 at our institute by a single surgeon. (2) The inclusion criteria were maximum urinary flow rate (Qmax) <15 ml/s, International Prostate Symptoms Score (IPSS) >15 or acute retention of urine with the failure of catheter trial or Acute retention of urine with prior history of severe bladder outlet obstruction. (3) Patients evaluated by: Digital rectal examination, uroflowmetry, IPSS, prostate-specific antigen (PSA), blood and urine routine tests, abdominal usage with trains rectal ultrasonography (TRUS), TRUS guided biopsies.Statistical Analysis Used:Not used.Results:(1) ThuLEP was a highly effective procedure as compared to all other procedures like HOLEP, TURP in terms of catheterization time, hospital stay, and drop in hemoglobin (Hb). (2) Catheterization time: 25.22 h (224 patients within 24 h and 12 patients within 48 h). (3) Hospital stay: 24–36 h 218 patients (92.3%), 36–48 h 18 patients (7.6%). (4) Drop in Hb: 0.8 ± 0.42 g/dl. (5) Average operative time: 56.91 min.Conclusions:Thulium LASER is a safe and highly effective LASER in terms of blood loss, speed of tissue resection, drop in serum PSA, and versatility of prostatic resection.

Laser ablation of the prostate: a safe effective treatment of obstructive benign prostatic disease

Laser ablation of the prostate: a safe effective treatment of obstructive benign prostatic disease

Long-Term Follow-Up and Risk of Cancer Death After Radiation for Post-Prostatectomy Rising Prostate-Specific Antigen

The results of salvage radiation therapy for rising prostate-specific antigen (PSA) levels after radical prostatectomy appear favorable, but the ultimate outcome is uncertain, given the relatively short follow-up in most studies. We report on a group of patients at a median follow-up of 13.9 years after salvage radiation therapy. From 1990 to 1995, 92 patients were referred postoperatively for radiation for a rising PSA level. PSA level at the time of referral ranged from 0.1 to 30.5 ng/ml (median, 1.5 ng/ml). The median time from surgery to radiation was 2.1 years (range,, 0.3-7.4 years). Radiation was directed to the prostatic fossa only with a median dose of 6,500 cGy (range, 6,000-7,000 cGy). Eighty-five patients experienced a PSA drop after radiation, as predicted by Gleason score and PSA level at the start of radiation. Five- and 10-year biochemical failure free survival (BFFS) was 35% and 26%, respectively, and overall survival was 86% and 67%, respectively. Median survival was 12.0 years, and median BFF was 2.3 years. The presurgery PSA level was not predictive, but the PSA level at the start of radiation predicted a response. Patients with Gleason 8 to 9 cancers had a significantly higher progression rate than those with lower Gleason scores. There were no significant differences in outcomes based on pathology findings (none vs. positive margins vs. positive seminal vesicles). Overall, 22 (24%) patients died directly from prostate cancer, resulting in a 10-year cancer-specific survival rate of 82%. Multivariate analysis risk factors for dying of cancer were Gleason's score (8 to 9) and PSA at the start of radiation therapy (>1.0 ng/ml). Patients have a good response to salvage radiation therapy. A small but durable subgroup appears to have permanent control. In those for whom therapy fails, radiation delays the need for other salvage therapy, indicating at least a transient benefit to most patients.

Developing Immunotherapy As Legitimate Therapy for Patients With Prostate Cancer

Developing Immunotherapy As Legitimate Therapy for Patients With Prostate Cancer

Contribution of a Single Repeat PSA Test to Prostate Cancer Risk Assessment: Experience from the ProtecT Study

ObjectiveTo examine whether a single repeat prostate-specific antigen (PSA) helps discriminate cancer from non–cancer-related PSA elevation. MethodsMen aged 50–70 yr (n=54,087) in a multicentre randomised controlled trial comparing treatments for localised prostate cancer were tested. A total of 4102 (7.6%) with an initial PSA in the range of 3–19.9ng/ml had repeat measurement (median interval: 50 d) followed by prostate biopsy. The decision to biopsy was based on the first PSA level. The outcome was the presence of prostate cancer on biopsy. ResultsMen with a 20% drop in PSA had a lower risk of cancer (odds ratio [OR]=0.43; 95% confidence interval [CI], 0.35–0.52; p<0.001) and high-grade cancer (OR=0.29; 95%CI, 0.19–0.44; p<0.001) compared to the rest of the cohort. The effect of percentage reduction was greater in men aged ≤60 yr than in those >60 yr. (OR for any cancer=1.6; 95%CI, 1.0–2.4; p=0.05; OR for high-grade cancer=2.9; 95%CI, 1.2–6.7; p=0.014). This equated to a risk reduction of high-grade cancer from 4% to 0.5%, 6% to 2%, and 15% to 2% in men ≤60 yr with an initial PSA of 3.0–3.99, 4.0–5.99, and ≥6ng/ml, respectively. No level of repeat PSA confidently predicted absence of cancer. ConclusionFollowing an initial PSA of 3.0–19.99ng/ml in men aged 50–70 yr, repeat PSA within 7 wk allows more accurate risk prediction that may assist in the decision-making as to whether or not to proceed with prostate biopsy.