Lower Serum Prostate-specific Antigen Levels Research Articles

Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Based Clinical Target Volume Delineation Guideline for Postprostatectomy Salvage Radiation Therapy: The PERYTON Guideline

Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) scan is the standard imaging procedure for biochemical recurrent prostate cancer postprostatectomy because of its high detection rate at low serum prostate-specific antigen levels. However, existing guidelines for clinical target volume (CTV) in prostate bed salvage external beam radiation therapy (sEBRT) are primarily based on experience-based clinical consensus and have been validated using conventional imaging modalities. Therefore, this study aimed to optimize CTV definition in sEBRT by using PSMA PET/CT-detected local recurrences (LRs). Patients with suspected LR on PSMA PET/CT postprostatectomy were retrospectively enrolled in 9 Dutch centers. Anonymized scans were centrally reviewed by an expert nuclear medicine physician. Each boundary of the CTV guideline from the Groupe Francophone de Radiothérapie en Urologie (GFRU) was evaluated and adapted to improve the accuracy and coverage of the area at risk of LR (CTV) on PSMA PET/CT. The proposed CTV adaptation was discussed with the radiation oncologists of the participating centers, and final consensus was reached. To assess reproducibility, the participating centers were asked to delineate 3 new cases according to the new PERYTON-CTV, and the submitted contours were evaluated using the Dice similarity coefficient (DSC). After central review, 93 LRs were identified on 83 PSMA PET/CTs. The proposed CTV definition improved the coverage of PSMA PET/CT-detected LRs from 67% to 96% compared with the GFRU-CTV, while reducing the GFRU-CTV by 25%. The new CTV was highly reproducible, with a mean DSC of 0.82 (range, 0.81-0.83). This study contributes to the optimization of CTV definition in postprostatectomy sEBRT by using the pattern of LR detected on PSMA PET/CT. The PERYTON-CTV is highly reproducible across the participating centers and ensures coverage of 96% LRs while reducing the GFRU-CTV by 25%.

Significance of extraprostatic extension by Grade Groups 1–3 prostatic carcinoma on needle biopsy

It is rare for extraprostatic extension (EPE) on biopsy to be seen with Grade Groups (GG) 1-3 (Gleason scores 3 + 3 = 6; 3 + 4 = 7; 4 + 3 = 7) prostatic adenocarcinoma, and there is no data whether this finding should be a contraindication for performing radical prostatectomy (RP). Thirty eight cases with GG 1-3 prostatic adenocarcinoma as the highest grade in the case with EPE on biopsy were identified from our consultation files. Highly unfavorable findings at RP were those that if they could have been predicted preoperatively, might have factored into the decision of whether to proceed with surgery. For these purposes, highly unfavorable pathology at RP was defined as either the presence of seminal vesicle invasion or lymph node metastases or GG5 (Gleason score 9-10). Among 37 patients with clinical follow-up data, 18 (49%) received radiation and/or hormonal therapy (RT/HT), 13 patients (35%) either underwent (n = 11) or are planning (n = 2) RP, and 6 patients (16%) received either ablation therapy or active surveillance. Based on the 11 RP pathology reports, 8 were GG2, one GG3 with tertiary pattern 5, and two GG3. Ten cases were reported to have EPE and six cases had positive margins. Only one had highly unfavorable pathology with pT3bN1 disease. The only difference between the RP and the RT/HT groups in their pretreatment parameters was the mean age of the RP patients was 61 compared with 69 for the RT/HT men (p = 0.02); the lack of many cases with highly unfavorable pathology at RP cannot be attributable to a selection bias of men with lower volume cancer on biopsy or lower serum prostate-specific antigen levels choosing RP over RT/HT. Despite EPE on biopsy, most men do not have highly unfavorable pathology at RP, and this treatment should remain an option in this setting.

68Ga-PSMA PET/CT-Based Atlas for Prostate Bed Recurrence After Radical Prostatectomy: Clinical Implications for Salvage Radiation Therapy Contouring Guidelines.

The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.

Urinary and sexual function changes in benign prostatic hyperplasia patients before and after transurethral columnar balloon dilatation of the prostate.

BACKGROUNDTransurethral columnar balloon dilatation of the prostate (TUCBDP) is a new surgical treatment, but its efficacy remains controversial because of limited clinical application.AIMTo investigate the clinical effect of TUCBDP for benign prostatic hyperplasia (BPH).METHODSOverall, 140 patients with BPH who underwent surgical treatment were included in the study. A random number table was used to divide the participants into study and control groups (n = 70 per group). The study group underwent TUCBDP. The prostate resection surgical time, intraoperative blood loss, bladder irrigation time, catheter indwelling time, length of hospital stay, International Prostate Symptom Score (IPSS), maximum urine flow rate (Qmax), residual urine volume (RUV), changes in the International Erectile Function Score (IIEF-5) score, serum prostate-specific antigen (PSA), quality of life (QOL) score, and surgical complications were compared in both groups.RESULTSThe operation time, intraoperative blood loss volume, bladder flushing time, urinary catheter indwelling time, and length of hospital stay were significantly lower in the study group than in the control group (P < 0.05). There were no significant differences in the IPSS, Qmax, and RUV measurements between the study and control groups (P > 0.05). However, at 3 mo post-surgery, the IPSS and RUV measurements were both lower (P < 0.05) and Qmax values were higher (P < 0.05) compared to the pre-surgery results in both groups. The IIEF-5 scores before and 3 mo after surgery were not significantly different between the study and control groups (P > 0.05). At 1 mo after surgery, the IIEF-5 score was higher in the study group than in the control group (P < 0.05). The serum PSA levels and QOL scores before treatment and at 1 and 3 mo after treatment were not significantly different between the study and control groups (P > 0.05). However, lower serum PSA levels and QOL scores were observed after 1 and 3 mo of treatment compared to pre-treatment levels in the study group (P < 0.05). The surgical complication rate of the study group (4.29%) was lower than that of the control group (12.86%; P < 0.05).CONCLUSIONTUCBDP for BPH and transurethral resection of the prostate can achieve better results, but the former method is associated with less surgical trauma.

KDM6B is an androgen regulated gene and plays oncogenic roles by demethylating H3K27me3 at cyclin D1 promoter in prostate cancer

Lysine (K)-specific demethylase 6B (KDM6B), a stress-inducible H3K27me3 demethylase, plays oncogenic or antitumoral roles in malignant tumors depending on the type of tumor cell. However, how this histone modifier affects the progression of prostate cancer (PCa) is still unknown. Here we analyzed sequenced gene expression data and tissue microarray to explore the expression features and prognostic value of KDM6B in PCa. Further, we performed in vitro cell biological experiments and in vivo nude mouse models to reveal the biological function, upstream and downstream regulation mechanism of KDM6B. In addition, we investigated the effects of a KDM6B inhibitor, GSK-J4, on PCa cells. We showed that KDM6B overexpression was observed in PCa, and elevated KDM6B expression was associated with high Gleason Score, low serum prostate-specific antigen level and shorted recurrence-free survival. Moreover, KDM6B prompted proliferation, migration, invasion and cell cycle progression and suppressed apoptosis in PCa cells. GSK-J4 administration could significantly suppress the biological function of KDM6B in PCa cells. KDM6B is involved in the development of castration-resistant prostate cancer (CRPC), and combination of MDV3100 plus GSK-J4 is effective for CRPC and MDV3100-resistant CRPC. Mechanism exploration revealed that androgen receptor can decrease the transcription of KDM6B and that KDM6B demethylates H3K27me3 at the cyclin D1 promoter and cooperates with smad2/3 to prompt the expression of cyclin D1. In conclusion, our study demonstrates that KDM6B is an androgen receptor regulated gene and plays oncogenic roles by promoting cyclin D1 transcription in PCa and GSK-J4 has the potential to be a promising agent for the treatment of PCa.

Total-Body 68Ga-PSMA-11 PET/CT for Bone Metastasis Detection in Prostate Cancer Patients: Potential Impact on Bone Scan Guidelines

Our purpose was to determine the relationship between serum prostate-specific antigen (PSA) level categories (<5, 5-10, 10-20, and >20 ng/mL) and the incidence of bone metastases detected by total-body 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT and to assess if expanding the 68Ga-PSMA-11 PET/CT imaging field to include the vertex and lower extremities (total-body acquisition) affects bone metastasis detection rates and patient management. Methods: This was a retrospective analysis of 388 prostate cancer patients enrolled in 5 prospective studies (NCT02940262, NCT03368547, NCT03042312, NCT04050215, and NCT03515577). All underwent 68Ga-PSMA-11 PET/CT scans acquired from vertex to toes for primary staging (n = 93/388, 24%), biochemical recurrence (BCR) localization (n = 225/388, 58%), or restaging metastatic disease (M1) before or during systemic therapy (n = 70/388, 18%) between September 2017 and May 2018. Results: In total, 321 of 388 patients (83%) had a positive 68Ga-PSMA-11 study. PSMA-positive bone lesions were found in 105 of 388 (27%) patients, with an incidence that was positively associated with serum PSA level (<10 ng/mL, 21%; 10-20 ng/mL, 41%; ≥20 ng/mL, 41%; P < 0.001). This association was maintained for all 3 indications: initial staging, BCR, and restaging M1. Bone metastases occurred most frequently in restaging M1, followed by BCR and initial staging. Bone metastasis incidence was not significantly associated with National Comprehensive Cancer Network risk score (P = 0.22). The average number of PSMA-positive regions also increased with serum PSA level (P < 0.001). Eighteen of 388 (5%) and 18 of 388 (5%) had lesions above the superior orbital ridge and below the proximal third of the femur, respectively. There was only 1 of 388 patients (0.26%) in whom the total-body PET acquisition had an impact on management. Conclusion: Bone metastases as assessed with 68Ga-PSMA-11 PET/CT are prevalent even in patients with low serum PSA levels. Therefore, current guidelines for bone assessments in prostate cancer patients should be revisited because 68Ga-PSMA-11 PET/CT may provide additional information for accurate bone staging at low serum PSA levels. Including the total body (from vertex to toes) in 68Ga-PSMA-11 PET/CT imaging revealed additional bone lesions in 6% of patients, but without significantly affecting patient management.

PSMA SPECT/CT with 99mTc-MIP-1404 in biochemical recurrence of prostate cancer: predictive factors and efficacy for the detection of PSMA-positive lesions at low and very-low PSA levels.

The in vivo expression of the prostate-specific membrane antigen (PSMA) can be investigated using the SPECT-suitable tracer 99mTc-MIP-1404. We investigated the performance of 99mTc-MIP-1404 PSMA SPECT/CT in the detection of PSMA-positive tumor lesions in patients suffering from biochemical recurrence of prostate cancer presenting with serum levels of the prostate-specific antigen (PSA) below 1ng/mL. We retrospectively analyzed 99mTc-MIP-1404-SPECT/CT scans of 50 patients (25 with low PSA levels between > 0.5 and 1ng/mL and 25 with very low PSA levels between 0.2 and 0.5ng/mL) that had undergone whole-body planar scintigraphy and SPECT/CT of the thorax, abdomen and pelvis 3-4h p.i. of 691 ± 72MBq 99mTc-MIP-1404. All datasets were evaluated for the presence and location of PSMA-positive tumor lesions, in which maximal standardized uptake values (SUVmax) were also measured. Based on the results of the quantitative evaluation as well as on biochemical and histological parameters, predictive factors for a positive 99mTc-MIP-1404 scan result were determined. The influence of 99mTc-MIP-1404 PSMA SPECT/CT on further therapy planning was assessed, based on the decision-making of the interdisciplinary tumor board. Pathological 99mTc-MIP-1404 uptake was detected in a total of 25 patients (50%). In the very low PSA subgroup, detection rates of PSMA-positive lesions suggestive of tumor recurrence were 44%, in the low-PSA subgroup 56%. Gleason scores ≥ 8 and the presence of antiandrogen deprivation therapy were further significant predictors of pathological 99mTc-MIP-1404 uptake. This was paralleled by significantly higher lesional SUVmax patients with PSA levels > 0.5ng/mL and Gleason scores ≥ 8 compared to those without these two features. Changes in therapeutic strategy following MIP-1404 imaging were recommended by the interdisciplinary tumor board in 25/50 of patients. 99mTc-MIP-1404 PSMA-SPECT/CT demonstrated a high performance in detecting PSMA-positive lesions suggestive of tumor recurrence in patients with biochemical recurrence of prostate cancer and low and very low serum PSA levels. Results from MIP-1404 PSMA SPECT/CT have therapeutic impact in one-half of the patients examined by this technology.

Low-serum prostate-specific antigen level predicts poor outcomes in patients with primary neuroendocrine prostate cancer.

The rarities of primary neuroendocrine prostate cancer (NEPC) and primary adenocarcinoma with neuroendocrine differentiation (NE differentiation) mean that their clinical characteristics have not been fully elucidated. A total of 449 patients with NEPC, including 352 cases of pure NEPC and 97 cases of NE differentiation, together with 408 629 cases of prostate adenocarcinoma at diagnosis were retrieved from the Surveillance, Epidemiology, and End Results program (2010-2015). Clinical parameters and prognoses were compared between patients with different histological types of NEPC using the χ2 test and Kaplan-Meier analysis, respectively. The prognostic value of prostate-specific antigen (PSA) in NEPC and adenocarcinoma was evaluated using Cox regression and the Kaplan-Meier method. Pure NEPC had higher rates of visceral metastases (brain, lung, and liver: 4.58%, 26.72%, and 36.64%, respectively) but a lower rate of bone metastasis (65.65%) compared with NE differentiation and prostate adenocarcinoma. Moreover, patients diagnosed with pure NEPC had a poorer outcome (median survival time: 10 months) compared with patients with NE differentiation (26 months) and prostate adenocarcinoma (median survival time not reached). Using PSA 4.1 to 10 ng/mL as the reference, the adjusted hazard ratios (HRs) for PSA lower than or equal to 4.0 ng/mL were 2.24 (95% confidence interval [CI]: 1.11-4.55, P = .025) in the NE differentiation group and 1.57 (95% CI: 1.11-2.23, P = .011) in the pure NEPC group. Patients with NE differentiation had different clinical characteristics and a better prognosis than patients with pure NEPC. In addition, low-serum PSA levels were associated with a poorer prognosis in patients with either NEPC or NE differentiation.

Prospective head-to-head comparative phase 3 study between 18F-fluciclovine and 68Ga-PSMA-11 PET/CT in patients with early biochemical recurrence of prostate cancer.

5014 Background: This is a prospective single-center, single-arm, head-to-head phase 3 study of paired 18F-fluciclovine (FACBC) and 68Ga-PSMA-11 (PSMA) PET/CT scans for localizing early biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) (NCT02940262). Methods: Fifty consecutive patients with BCR and prostate specific antigen (PSA) levels ranging from ≥0.2 to ≤2.0 ng/mL without any prior salvage therapy were included. All patients underwent FACBC and PSMA PET/CT scans within ≤15 days. PET/CT scans were each interpreted by 3 independent blinded expert readers not involved in study design and data acquisition. Region consensus interpretation (T,N,M1a,M1b,M1c) was generated based on majority rule in cases of reader disagreement (2 vs 1). PET/CT scans were considered as positive if any region was rated as positive. Detection rates per-patient and per-region served as primary study endpoint. Results: Median time interval between the 2 scans was 6 days (range 1-15). Median PSA level at the time of imaging was 0.50 ng/ml (mean 0.63; range 0.2-2.0 ng/ml). The detection rates were significantly lower with FACBC than with PSMA PET/CT per-patient (26% vs 56%; p = 0.003) and per-region for pelvic nodes (N) (8% vs 30%; p = 0.003) or any extra-pelvic lesions (M) (0% vs 16%; p = 0.008). Reader agreement for PSMA PET/CT image interpretations was significantly higher than for FACBC PET/CT (0.67 vs 0.20; p = 0.015). Conclusions: In patients with BCR and low serum PSA levels after RP, PSMA PET/CT demonstrates higher detection rates and superior reader agreement when compared with FACBC PET/CT. Therefore, PSMA PET/CT should be the imaging modality of choice in patients with early BCR. Clinical trial information: NCT03515577.

Extensive Metastases in Prostatic Carcinoma with Normal Prostate-Specific Antigen and Raised Carcinoembryonic Antigen – Small Cell Carcinoma of Prostate: A Rare Entity

AbstractSmall cell carcinoma of prostate is a neuroendocrine tumor of prostate seen in 0.5%–2% of men with carcinoma prostate. Prostate-specific antigen (PSA) is a common tumor marker which is often raised in prostatic carcinoma. However, prostatic carcinoma can progress with normal or low serum PSA levels at the time of diagnosis. Carcinoembryonic antigen (CEA) is a tumor marker of different carcinomas. Small cell carcinoma prostate is a highly aggressive tumor which can progress with normal or low serum PSA levels and raised CEA levels. We report a case of 65-year-old male with enlarged prostate with extra-prostatic spread, hepatic metastases, metastatic retroperitoneal and pelvic lymph nodes, osteoblastic metastasis in lumbar spine with normal serum PSA, and raised CEA levels. Prostatic biopsy was suggestive of small cell carcinoma.

18F-Fluorocholine PET/MRI in Restaging of Prostatic Carcinoma in Relation to PSA Level and Detection of Active Disease.

To evaluate our own experience with 18F- fluoromethylcholine-(FCH)-positron-emission tomography combined with magnetic resonance imaging (PET/MRI) in restaging of patients with prostatic carcinoma and elevated serum prostate-specific antigen (PSA) level. The analysis was performed on a sample of 100 male patients who underwent 18F-FCH-PET/MRI, with a mean age of 63.2 years (range=47-78 years). The imaging was performed using an integrated PET/MRI hybrid system after intravenous application of 18F-FCH at a dose of 1.25 MBq/kg. The number and sites of pathological accumulation of FCH related to local recurrence, nodal spread and skeletal metastases were compared to corresponding MRI findings; furthermore, the relation of PSA level and presence of FCH accumulation in tumorous tissue was assessed; finally we correlated the findings of different sites of metastatic involvement. In patients with a PSA level up to 2 ng/ml, accumulation in tumorous tissue of local recurrence or metastases was found in 83.33% in cases of biochemical relapse, and in patients with PSA level above 5 ng/ml in 100% of cases. In general, we found any finding explained rise of PSA level in 94% of patients. 18F-FCH-PET/MRI using an integrated system with 1,25 MBq/kg dosing of FCH is a valuable tool in evaluation of restaging in patients with prostatic carcinoma, with high detection rate even in those with a low serum PSA level.

Is Serum Prostate-Specific Antigen a Reliable Prostate Cancer Marker in Liver Transplant Candidates.

In this study, we aimed to determine whether the prostate-specific antigen level is a reliable marker of prostate cancer in patients with hepatic insufficiency, based on evaluation of alterations in serum prostate-specific antigen levels after liver transplant in patients with hepatic insufficiency. Medical records of all patients who underwent liver transplant at our hospital between January 2003 and June 2017 were retrospectively reviewed. Male patients who were > 40 years old with available pre- and posttransplant serum total prostate-specific antigen levels were included in the study. Our study included 36 male patients with a mean age of 54.6 ± 5.3 years (range, 45-73 y) at the time of liver transplant. The mean pretransplant serum total prostate-specific antigen level was 0.75 ± 0.77 ng/mL, which was significantly lower than the mean posttransplant level of 1.29 ± 1.57 ng/mL (P < .05). The pretransplant serum total prostate-specific antigen level was measured a mean of 4.9 ± 5.4 months before liver transplant versus a mean 27.6 ± 16.3 months after transplant. Prostate-specific antigen velocity was 0.2 ng/mL/year. Biochemical tests of liver function, including the mean serum levels of bilirubin, international normalized ratio, and albumin, were normal after liver transplant at 1.37 ± 2.33 mg/dL, 1.22 ± 0.36, and 4.16 ± 0.69 g/dL, respectively. Serum prostate-specific antigen levels may decrease in patients with hepatic insufficiency/cirrhosis; therefore, a low serum prostate-specific antigen level may not be a reliable marker for excluding prostate cancer in such patients. Transplant surgeons and clinicians must be aware of this so that all male transplant candidates > 40 years old are evaluated via digital rectal examination, regardless of the serum prostate-specific antigen level.

Impact of poor glycemic control of type 2 diabetes mellitus on serum prostate-specific antigen concentrations in men.

BackgroundTo evaluate the impact of poor glycemic control of type 2 diabetes mellitus (T2DM) on serum prostate-specific antigen (PSA) concentrations in men.MethodsWe performed a prospective analysis of 215 consecutive patients affected by erectile dysfunction (ED). ED was evaluated using the IIEF-5 questionnaire and the poor glycemic control (PGC) of T2DM was assessed according to the HbA1c criteria (International Diabetes Federation). Patients were divided into PGC group (HbA1c ≥ 7%) and control group (CG) (HbA1c < 6%). Correlations between serum HbA1c levels and various variables were evaluated and multivariate logistic regression analyses were carried out to identify variables for PGC.ResultsWe compared 110 cases to 105 controls men ranging from 44 to 81 years of age, lower PSA concentrations were observed in men with PGC (PGC mean PSA: 0.9 ng/dl, CG mean PSA: 2.1 ng/dl, p < 0.001). Also mean prostate volume was 60% was smaller among men with PGC compared with men with CG (PGC mean prostate volume: 26 ml, CG prostate volume: 43 ml, p < 0.001). A strong negative correlation was found between serum HbA1c levels and serum PSA (p < 0.001 and r = −0.665) concentrations in men with PGC. We also found at the multivariate logistic regression model that PSA, prostate volume and peak systolic velocity were independent predictors of PGC.ConclusionOur results suggest that there is significant impact of PGC on serum PSA levels in T2DM. Poor glycemic control of type 2 diabetes was associated with lower serum PSA levels and smaller prostate volumes.

Recurrent Prostate Cancer Presenting as Multiple Lung Metastases with a Low Serum Prostate-specific Antigen Level 5 Years after Prostatectomy: A Case Report

Prostate-specific antigen (PSA) is a glycoprotein produced by prostatic duct and acinar epithelial cells and the most commonly used marker for diagnosing prostate cancer, and for monitoring its progression and recurrence. Here, we describe a 76-year-old patient with recurrent prostate cancer who developed isolated hematogenous pulmonary metastases with a normal serum PSA level 5 years after radical prostatectomy. Immunohistochemical (IHC) analysis of a transbronchial lung biopsy specimen revealed tumor cells positive for PSA and prostatic acid phosphatase. After 2 months of maximal androgen blockade, the metastatic pulmonary nodules showed near-complete regression. In conclusion, metastases of prostate adenocarcinoma may occur despite low serum PSA levels, and, if warranted clinically, IHC staining or other serological markers for prostate adenocarcinoma should be considered when evaluating metastatic carcinoma from an unknown primary lesion in males with low serum PSA levels. (Korean J Med 2015;89:238-242)

Combined tests of prostate specific antigen and testosterone will improve diagnosis and monitoring the progression of prostate cancer.

Prostate-specific antigen (PSA) testing has been widely used to screen men for prostate cancer (PCa) and to monitor PCa progression. However, more studies have shown that around 15% of men with low or normal PSA levels have PCa. In this study, we aimed to investigate the relationship of androgen and PSA levels and to better understand the reason that some PCa patients have low serum PSA values. The in vitro data demonstrated that cultured LNCaP cells ceased to produce PSA after androgen withdrawal and resumed PSA production after androgen was re-added. The in vivo experiment results showed that 48% of PCa xenografts carrying mice have serum PSA level lower than 4 ng ml−1. The serum PSA levels increased significantly with rises in testosterone (T) levels 1 week after T pellet implantation. These data indicated that the androgen is a key factor controlling the production of PSA. Low serum PSA levels in mice with PCa xenografts are associated with low serum T levels. Raising serum T levels in tumor caring mice will also significantly increase serum PSA level. This may have clinical implications when screening PSA in men, who have occult PCa.

Neuroendocrine prostate cancer: subtypes, biology, and clinical outcomes.

Neuroendocrine prostate cancer (NEPC) encompasses various clinical contexts, ranging from the de novo presentation of small cell prostatic carcinoma to a treatment-emergent transformed phenotype that arises from typical adenocarcinoma of the prostate. The development of resistance to potent androgen receptor signaling inhibition may be associated with the emergence of aggressive phenotype, advanced castration-resistant NEPC. Clinically, small cell prostate cancer and NEPC are often manifested by the presence of visceral or large soft tissue metastatic disease, a disproportionately low serum prostate-specific antigen level relative to the overall burden of disease, and a limited response to targeting of the androgen signaling axis. These tumors are often characterized by loss of androgen receptor expression, loss of retinoblastoma tumor suppressor copy number or expression, amplification of Aurora kinase A and N-Myc, and activation of the PI3K pathway. However, a consensus phenotype-genotype definition of NEPC has yet to emerge, and molecularly based biomarkers are needed to expand on traditional morphologic and immunohistochemical markers of NEPC to fully define the spectrum of this aggressive, androgen receptor-independent disease. Emerging studies implicate a shared clonal origin with prostatic adenocarcinoma in many cases, with the adaptive emergence of unique cellular programming and gene expression profiles. Ongoing clinical studies are focused on developing novel targeted therapeutic approaches for this high-risk, lethal subset of disease, to improve on the limited durations of response often observed with traditional platinum-based chemotherapy.

Reply

Thank you for your great comments. Obesity has been shown to be associated with lower serum prostate specific antigen (PSA) levels mainly because of increased plasma volume among men with large body habitus. Various studies have previously reported lowered PSA concentrations linked to obesity among men undergoing population-based screening, whose mean PSA is generally low (1.0 ng/mL or so). Editorial CommentUrologyVol. 81Issue 4PreviewAs the controversy surrounding screening for prostate cancer continues to evolve, efforts are being made to improve detection of life-threatening cancers while avoiding detection of those that are not dangerous. This problem might be more difficult for obese men whose prostate-specific antigen (PSA) level might go up or down depending on different factors. Studies have found that higher levels of body mass index (BMI) are associated with lower serum PSA levels. At the same time, increasing body weight is associated with increasing prostate volume, which increases PSA. Full-Text PDF

Editorial Comment

As the controversy surrounding screening for prostate cancer continues to evolve, efforts are being made to improve detection of life-threatening cancers while avoiding detection of those that are not dangerous. This problem might be more difficult for obese men whose prostate-specific antigen (PSA) level might go up or down depending on different factors. Studies have found that higher levels of body mass index (BMI) are associated with lower serum PSA levels. At the same time, increasing body weight is associated with increasing prostate volume, which increases PSA. These paradoxical effects could influence the detection of prostate cancer in a group of men who might have more aggressive disease, particularly at low PSA levels. In this issue of Urology, Dr. Kim and his colleague questioned whether PSA density (PSAD) might be more useful than serum PSA in deciding which men warrant a prostate biopsy. They measured serum PSA and determined BMI on nearly 2300 Korean men with a serum PSA less than 3 ng/mL. Their results showed that both PSA and PSAD had a negative correlation with BMI. However, PSA was useful only for men with a BMI greater than 25 kilograms per meter squared, whereas PSAD showed a better correlation with all 3 weight groups. Prostate-specific Antigen Density: A Better Index of Obesity-related PSA Decrease in Ostensibly Healthy Korean Men With a PSA <3.0 ng/mLUrologyVol. 81Issue 4PreviewTo determine whether prostate-specific antigen density (PSAD) has a more significant correlation with obesity than prostate-specific antigen (PSA). Full-Text PDF ReplyUrologyVol. 81Issue 4PreviewThank you for your great comments. Obesity has been shown to be associated with lower serum prostate specific antigen (PSA) levels mainly because of increased plasma volume among men with large body habitus. Various studies have previously reported lowered PSA concentrations linked to obesity among men undergoing population-based screening, whose mean PSA is generally low (1.0 ng/mL or so). Full-Text PDF

Thiosulfate in urine as a facilitator in the diagnosis of prostate cancer for patients with prostate-specific antigen less or equal 10 ng/mL

The aim of this study was to examine the level of thiosulfate in the urine of prostate cancer (PCa) patients and evaluate its usefulness in the diagnosis and monitoring of prostate malignant transformation. Thiosulfate is a naturally occurring product of hydrogen sulfide (H2S) metabolism. H2S is involved in many physiological and pathological processes including inflammation and tumorigenesis. The determination of thiosulfate in the urine of PCa patients and healthy controls was performed by reverse-phased liquid chromatography using 2-chloro-1-methylquinolinium tetrafluoroborate as a derivatization reagent. Thiosulfate concentrations were normalized to urinary creatinine levels to compensate for variable diuresis. In the urine samples of PCa patients, the mean thiosulfate level was almost 50 times higher than in the control groups and five times higher than in the benign prostatic hyperplasia group. The level of thiosulfate did not correlate with the serum prostate-specific antigen (PSA) level or PSA density. Neither tumor stage nor tumor grade was associated with thiosulfate level. The results suggest that thiosulfate concentration in urine may be a good facilitator in the diagnostics of PCa. The predictive accuracy of this method is particularly valuable for the diagnosis of patients with low serum PSA level and negative digital rectal examination and transrectal ultrasound results.

Priapism as the Initial Manifestation of a Penile and Lower Limb Cutaneous Metastasis of Prostate Adenocarcinoma With Low Serum PSA Level

Penile and/or cutaneous metastases from prostate adenocarcinoma rarely occur. Here, we detail the case of a 78-year-old man suffering from priapism caused by metastatic prostate cancer with both penile and lower limb cutaneous spread. His serum prostate-specific antigen level was 0.09 μg/L when priapism developed. Corpora cavernosa biopsy was refused by the patient and radical penectomy was performed. Postoperative pathologic and immunohistochemical studies revealed undifferentiated prostate adenocarcinoma cells growing in corpora cavernosa. Two months later, the patient presented with multiple, erythematous nodules over the right lower leg. The prostate-specific antigen level was found to be 0.264 μg/L. Biopsy of a skin nodule revealed neoplastic cells consistent with metastatic prostate adenocarcinoma. This is the first known case of metastatic prostate cancer found in both penis and skin with a low serum prostate-specific antigen level. Priapism presented as the initial clinical manifestation of metastatic prostate cancer.