Prostate-specific Antigen Levels In Patients Research Articles

Androgen Receptor Signaling Inhibitor Withdrawal Syndrome After Castration-resistant Prostate Cancer.

Androgen-deprivation therapy is an extremely effective treatment for progressive prostate cancer. Previously, the first-line treatment for progressive prostate cancer was combined androgen blockade (CAB). If the disease progressed to castration-resistant prostate cancer, the administration of androgen receptor signaling inhibitors (ARSIs) was recommended. When elevated serum prostate-specific antigen (PSA) levels are seen during CAB treatment, it is important to suspect antiandrogen withdrawal syndrome (AWS), discontinue CAB, and monitor the changes in the serum PSA levels. If a reduction in the patient's PSA levels is subsequently observed, antiandrogens should be discontinued and the patient should be followed, but if their PSA level rises they should be transitioned to ARSI treatment. Recently, there have been reports of withdrawal syndrome (WS) after ARSI treatment. With the increased use of ARSIs, such as abiraterone acetate, enzalutamide, apalutamide, and dalorutamide, it is necessary to consider ARSI WS when a patient's serum PSA level increases during ARSI treatment. Unnecessary treatment can be avoided if the confirmation of ARSI WS is prioritized. Conversely, if it is not confirmed there is a risk that second-line treatment will be delayed. This is a review of recent studies of ARSI WS. It also discusses future prospects in this field.

Recurrence of mucinous prostate cancer in rectal wall due to needle-track seeding from previous transrectal prostate biopsy.

Needle-track seeding of prostate cancer into the rectal wall following transrectal prostate biopsy is exceedingly rare. We report a case of mucinous prostate cancer recurrence in the rectal wall due to biopsy needle seeding, discovered after robot-assisted radical prostatectomy. A 67-year-old man underwent robot-assisted radical prostatectomy for mucinous prostate cancer (clinical stage T2cN0M0, Gleason score of 4 + 4, and initial prostate-specific antigen level of 8.8 ng/mL). Five years postoperatively, endoscopy revealed a rectal tumor, which was diagnosed as needle-track seeding from the previous transrectal prostate biopsy. Following resection of this rectal tumor, the patient's prostate-specific antigen level fell to <0.008 ng/mL. No signs of recurrence or metastasis were observed 3 months postoperatively. While rare, transrectal prostate biopsies can pose a small risk of needle-track seeding into the rectal wall. Endorectal examination should be considered if biochemical recurrence of prostate cancer occurs following radical prostatectomy.

Plain language summary: Does the amount of time it takes for prostate-specific antigen to double affect how long men with nonmetastatic castration-resistant prostate cancer live and their healthcare costs?

This is a plain language summary of a research article originally published in Clinical Genitourinary Cancer. The original article described the effect of rapidly rising prostate-specific antigen (PSA) levels on how long men with a type of advanced prostate cancer live and their healthcare costs. The prostate is a part of the male body that helps make semen. PSA is a protein produced by the prostate that can show how advanced prostate cancer has become. One measure of prostate cancer growth is assessing how quickly a patient's PSA level doubles. This is known as the PSA doubling time (PSADT). People with a shorter PSADT usually have faster-growing prostate cancer compared with people who have a longer PSADT of more than 12months (long PSADT). Researchers wanted to know if PSADT can predict cancer spread (known as metastasis) or death for people with a type of advanced prostate cancer called non-metastatic castration-resistant prostate cancer (nmCRPC). Researchers also wanted to know if PSADT can predict healthcare costs. This could help doctors choose the right treatment for their patients with nmCRPC. This was a real-world study, not a clinical trial. This means that researchers looked at what happened when men received the treatments prescribed by their own doctor as part of their usual healthcare treatment. In this study, researchers used insurance claim information. Researchers looked at information for 2800men with nmCRPC. Six out of every 10men (60%) had a long PSADT of more than 12months. Researchers found that it took longer for the cancer to spread to other parts of the body in men with a longer PSADT than men with PSADT of 12months or less. Researchers also found that men with a longer PSADT lived longer than men with PSADT of 12months or less. The long PSADT group had fewer healthcare visits overall than men with PSADT of 10months or less. Over time, it cost less to treat men with a long PSADT than men with PSADT of 10months or less. Generally, if PSADT was shorter, patients tended to do worse. In this real-world study, researchers found that men with nmCRPC lived longer and had lower healthcare costs if they had a long PSADT of more than 12months compared with men who had a shorter PSADT. Men with nmCRPC and a shorter PSADT may benefit from approved treatments that slow cancer spread and help them live longer. However, these treatments may have side effects and cost more than standard treatment. Doctors take all these things into account when choosing treatments for their patients. Most men in this study had a long PSADT of more than 12months. Standard treatment may be the right choice for them because they are more likely to have better outcomes than men with a shorter PSADT.

Prostate-specific antigen reduction after capecitabine plus oxaliplatin chemotherapy: A case report

Prostate cancer (PC) is currently the most common malignant tumor of the genitourinary system in men. Radical prostatectomy (RP) is recommended for the treatment of patients with localized PC. Adjuvant hormonal therapy (AHT) can be administered postoperatively in patients with high-risk or locally advanced PC. Chemotherapy is a vital remedy for castration-resistant prostate cancer (CRPC), and may also benefit patients with PC who have not progressed to CRPC. A 68-year-old male was admitted to our hospital because of urinary irritation and dysuria with increased prostate-specific antigen (PSA) levels. After detailed examination, he was diagnosed with PC and treated with laparoscopic RP on August 3, 2020. AHT using androgen deprivation therapy (ADT) was performed postoperatively because of the positive surgical margin, extracapsular extension, and neural invasion but lasted only 6 mo. Unfortunately, he was diagnosed with rectal cancer about half a year after self-cessation of AHT, and was then treated with laparoscopic radical rectal resection and adjuvant chemotherapy using the capecitabine plus oxaliplatin (CapeOx) regimen. During the entire treatment process, the patient's PSA level first declined significantly after treatment of PC with laparoscopic RP and ADT, then rebounded because of self-cessation of ADT, and finally decreased again after CapeOx chemotherapy. CapeOx chemotherapy can reduce PSA levels in patients with high-risk locally advanced PC, indicating that CapeOx may be an alternative chemotherapy regimen for PC.

Vaccine-Related Lymph Nodes: The Emerging Pitfalls of 18F-Fluorocholine and 68Ga-PSMA-11 PET/CT in the Era of COVID-19 Vaccination.

PurposeVaccination against coronavirus disease 2019 (COVID-19) is currently under worldwide deployment. The consequences of this vaccination can be seen in radiology and nuclear medicine explorations with visualization of axillary lymph nodes (LNs), as observed on ultrasonography, MRI, or 18F-FDG PET/CT.We aimed to evaluate on PET/CT the incidence of vaccine-related LNs and their characteristics after COVID-19 vaccination, using several radiopharmaceuticals different from 18F-FDG.Patients and MethodsBetween February and July 2021, all consecutive patients undergoing a whole-body PET/CT for any indication using a different radiopharmaceutical from 18F-FDG were eligible for inclusion if they had received at least 1 dose of the COVID-19 vaccine. The radiopharmaceutical administered and vaccine type were recorded for each patient. The incidence of positive vaccine-related axillary and supraclavicular LNs on PET/CT was our primary finding, along with the nodes characteristics. Statistical analyses were performed for patients with prostate cancer (PCa) to determine certain interaction factors that were associated with the detection of vaccine-related LNs.ResultsOf the 226 patients in our cohort study, 120 patients underwent an 18F-fluorocholine PET/CT, 79 a 68Ga-PSMA-11 PET/CT, 6 an 18F-FDOPA PET/CT, and 21 a 68Ga-DOTATOC PET/CT. A total of 67.3% of patients (152/226) received BNT162b2mRNA (Pfizer-BioNTech), 26.5% (60/226) ChAdOx1-S (AstraZeneca), 4.9% (11/226) mRNA-1273 (Moderna), and 1.3% (3/226) Ad26.COV2.S (Janssen). The incidence of positive vaccine-related axillary and supraclavicular LNs was 42.5% (51/120 patients) on PET/CT using 18F-fluorocholine and 12.7% (10/79 patients) with 68Ga-PSMA-11. None of our patients undergoing 18F-FDOPA or 68Ga-DOTATOC PET/CT presented any vaccine-related lymphadenopathy. Vaccine-related LNs were statistically associated with the nature of the radiopharmaceutical (P < 10−4), with the number of vaccine doses received (P = 0.041), with a short delay between vaccination and PET/CT realization (P < 10−5), and with a higher prostate-specific antigen level for patients with PCa (P = 0.032), but not with age or vaccine type. The vaccine-related nodes appeared in 85% of the cases, in the 30 days after vaccine injection, were limited in size and uptake, and were most often limited to the axilla level 1 area.ConclusionsDetecting positive LNs after COVID-19 vaccination is not an exclusive 18F-FDG PET/CT pattern but is common on 18F-fluorocholine and possible on 68Ga-PSMA-11 PET/CT. Confronting PET/CT findings with clinical data (such as date and site of injection) seems essential in the current pandemic context, just as it does for the radiopharmaceuticals used in PCa to avoid PET/CT misinterpretation and incorrect patient treatment. For 18F-FDOPA or 68Ga-DOTATOC PET/CT, this seems to have a lesser impact.

Prostate-specific antigen levels in patients with risk factors for prostate carcinoma disorders

ABSTRACT Objective: To verify the association between the prostate-specific antigen (PSA) serum concentration and the presence of risk factors for prostate diseases in adult patients with urogenital infections. Materials and methods: Analytical cross-sectional study of PSA in 60 patients aged 40 to 65 years, from January to December 2013. PSA quantification was performed in serum by solid-phase chemiluminescence in two label cycles: 1. mouse monoclonal antibody (mAb); and 2. goat polyclonal antibody (pAbs). After each cycle the free antigen was removed. The readings were taken on the INMULITE ONE Siemens® automated equipment. From the PSA, 0.0-2.5 ng/ml was used to calculate the antigen distribution trend, and a bivariate statistical analysis of PSA was as opposed to previous exams, and endogenous and environmental risk factors detected. Results: Patients between 50-60 years of age, with a family history of urogenital and sexually transmitted infections, toxic habits, and exposure to occupational risk prevailed. Sixty-two percent of patients presented normal PSA levels, and the remaining presented slightly elevated and very high PSA levels. In the statistical analysis, a significant association (p < 0.001) of PSA was found as opposed to previous tests. A significant association (p = 0.001) was also found between PSA versus age, family history, personal pathological history, toxic habits, and risk exposure. Conclusion: The high association rate found between PSA versus age and other risk factors could be used as a predictive value for prostate cancer (Pca) or other prostate disorders.

Incidentally Detected 18F-FDG-Avid Prostate Cancer Diagnosed Using a Novel Fusion Biopsy Platform

Background: Localized prostate cancer rarely undergoes a shift in metabolism towards aerobic glycolysis, a process known as the Warburg Effect. Because of this, positron emission tomography (PET)/CT imaging using 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) is uncommonly used to evaluate patients with early-stage prostate cancer. However, men undergoing an 18F-FDG PET/CT for unrelated reasons will on occasion be found to have radiotracer uptake within the prostate gland. The appropriate work-up of these patients is poorly defined. Case Presentation: We present the case of a 61-year-old man with a history of tonsillar squamous cell carcinoma who was incidentally found on 18F-FDG PET/CT to have a hypermetabolic nodule within the prostate. The patient's prostate-specific antigen level was 2.1 ng/cc and digital rectal examination revealed no abnormalities. The patient underwent a targeted prostate biopsy of the lesion using the KOELIS Trinity biopsy platform, which uniquely allows for the real-time overlay of transrectal ultrasonography and PET/CT images. Targeted biopsy revealed Gleason score 4 + 3 = 7 (grade group 3) prostate cancer. Conclusion: Although the incidental detection of 18F-FDG uptake within the prostate is uncommon, more than half of all patients will be found to have prostate cancer. Based on this case and our review of the available medical literature, it is our belief that men with incidentally detected uptake of 18F-FDG within the prostate should undergo further evaluation with a prostate biopsy. This recommendation is supported by data suggesting that 18F-FDG-avid prostate cancer represents a more aggressive clinical phenotype.

The prognostic value of mid-treatment prostate-specific antigen level in patients receiving salvage radiotherapy.

289 Background: Salvage radiotherapy (SRT) may be employed as a potentially curative intervention for patients experiencing biochemical failure (serum prostate-specific antigen [PSA] ≥ 0.2 ng/mL) after prostatectomy for localized prostate cancer. Patients not showing a favorable response to SRT alone may require additional therapies and may benefit from earlier identification of this need. Methods: 131 consecutive patients received SRT during the timeframe of this study. 76 were deemed eligible based on the following criteria: prostatic adenocarcinoma diagnosis receiving SRT, no clinical evidence of metastasis, no hormone use prior to/during SRT, serum PSA measurement halfway through SRT, and minimum follow-up time of 3 months. Median follow-up time was 51.6 months. Eligible patients were divided into three groups based on PSA response by the midpoint of treatment: no change, decrease, or increase in PSA. The primary endpoint of the study was clinical failure (measured from SRT completion), defined as serum PSA value ≥0.2ng/mL above the post-radiotherapy nadir, initiation of androgen deprivation therapy, development of bone metastasis, or death from prostate cancer. Results: 13.1% experienced no change in PSA halfway through SRT (group 0), 68.4% of patients experienced a decrease (group 1), 18.4% experienced an increase (group 2). Four-year freedom from clinical failure was 60.0% for group 0, 58.3% for group 1, and 41.7% for group 2. Median time to clinical failure was 71.7 months for group 1, 26.8 months for group 2, and was not reached for group 0. Pairwise multiple comparison demonstrated a significant difference in four-year freedom from clinical failure between groups 1 and 2 (p = 0.036). Conclusions: These data strongly suggest that changes in PSA are apparent midway through SRT and are associated with 4-year freedom from clinical failure. Further study is warranted to determine whether mid-treatment PSA during SRT may be used to identify a subset of patients that may benefit from treatment intensification.

The prognostic value of mid-treatment prostate-specific antigen level in patients receiving salvage radiotherapy.

e17055Background: Salvage radiotherapy (SRT) may be employed as a potentially curative intervention for patients experiencing biochemical failure (serum prostate-specific antigen [PSA] ≥ 0.2 ng/mL)...

Abiraterone acetate withdrawal syndrome: Speculations on the underlying mechanisms.

A 72-year-old man initially presented with lumbar and right chest pain, but was later found out to also have an elevated prostate-specific antigen (PSA) level at 2,000.0 ng/ml. Further evaluation disclosed metastatic prostate cancer involving the bones and lymph nodes. The patient was initially treated with combined androgen blockade (CAB) with leuprolide acetate and bicalutamide. After 6 months of CAB, the patient's PSA level began to rise from the nadir (85.1 ng/ml) to 113.3 ng/ml. Bicalutamide was withdrawn in anticipation of anti-androgen withdrawal syndrome and the PSA level declined temporally. However, it increased up to 517.0 ng/ml thereafter. Consequently, a year after CAB, abiraterone acetate (AA) was initiated at a standard dose of 1,000 mg daily in combination with 10 mg of prednisolone. PSA rapidly decreased to the nadir of 20.1 ng/ml thereafter. The PSA level remained stable until 2 years after AA administration. However, he decided to reduce the dose of AA to half of the standard dose (500 mg daily). Contrary to our expectations, the serum PSA level promptly decreased to a nadir of 8.1 ng/ml. Thereafter, the PSA level remained stable until 3 years and 9 months after AA administration. Subsequently, the patient stopped taking AA and prednisolone. However, to our surprise, the patient's serum PSA level decreased further to <1.0 ng/ml after AA discontinuation. His PSA remained <1.0 ng/ml without clinical or radiological progression for 1 year after AA withdrawal. Recently, it was reported that cessation of AA is associated with AA withdrawal syndrome in metastatic castration-resistant prostate cancer, defined as a PSA decrease after AA discontinuation, mimicking anti-androgen withdrawal syndrome. In the present study, explanations of the mechanisms underlying this phenomenon were explored, including mutant AR activation by alternative ligands.

Prognostic parameter for high risk prostate cancer patients at initial presentation.

High-risk prostate cancer can be defined by a patient's Gleason score (GS), prostate-specific antigen (PSA) level, and clinical T (cT) stage, but a novel marker is needed due to heterogeneity of the disease. In this study, we evaluated whether intraductal carcinoma of the prostate (IDC-P) confirmed by needle biopsy is an adverse prognostic parameter for progression-free survival (PFS) and cancer-specific survival (CSS) in patients with high-risk prostate cancer. We retrospectively evaluated 204 patients with high-risk prostate cancer treated by radical prostatectomy from 1991 to 2005 at Nagoya University and its affiliated hospitals. Data on each patient's PSA level, biopsy GS, cT stage, presence of Gleason pattern 5, presence of IDC-P, percentage of the core involved with cancer, and maximum percentage of the core involved with cancer were analyzed. The median follow-up period was 108 months (range, 11-257 months). Forty-eight patients (24%) showed disease progression. Thirty-four patients (17%) died of the disease during follow-up. The IDC-P component was detected in 74 (36%) needle biopsy samples. The 5-, 10-, and 15-year CSS rates of the IDC-P-negative cases were 3.2%, 9.0%, and 23.7%; the corresponding rates of the IDC-P-positive cases were 23.9%, 33.7%, and 52.7%, respectively (P = 0.0001). In the Fine and Gray's model for PFS, IDC-P, maximum percentage of the core involved with cancer, and cT stage were significantly associated (P = 0.013, P = 0.003, P = 0.007). In the Fine and Gray's model for CSS, only IDC-P was significant (P = 0.027). In a multivariate Cox regression analysis, IDC-P (P = 0.04; hazard ratio [HR], 1.95) and maximum percentage of the core involved with cancer (P = 0.021; HR, 0.43) were significant factors in predicting overall survival (OS). The presence of IDC-P in a needle biopsy was a prognostic factor for PFS, CSS, and OS in patients with high-risk prostate cancer who underwent radical prostatectomy. Multimodal pre-and/or post- surgical therapy may be needed when IDC-P is found in a needle biopsy specimen.

The Effect of a Pure Anti-inflammatory Therapy on Reducing Prostate-specific Antigen Levels in Patients Diagnosed With a Histologic Prostatitis

To investigate the effectiveness and the tolerability of a combined pure anti-inflammatory therapy not associated with antibiotics on reducing PSA levels. Patients with a previous biopsy negative for prostate cancer and showing persisting level of prostate-specific antigen (PSA) greater than 4 ng/dl were recruited. The specimens of previous biopsy were classified as benign or showing inflammation. Eligible patients were divided into 2 equal groups. In group 1, men with histological findings of inflammation at the previous prostatic biopsy were selected, in group 2, patients without such findings were included. Men of both groups were treated for 3 months with the same pure anti-inflammatory scheme including nimesulide, Serenoa repens, bromelain, and quercetin. After treatment, PSA levels were determined again. Independently by the second PSA determinations, all patients underwent a second 16 core biopsy. A total of 140 patients were enrolled. No adverse reactions were reported. Total PSA lowered from 7.3 ng/mL at baseline to 4.6 ng/mL (P <.0001) after treatment in group 1, and from 7.2 ng/mL to 7 ng/mL (P = .0005) in group 2. Overall, we diagnosed a prostate cancer at the second biopsy in 27 men among 140 (19.2%). The percentage of cancer at re-biopsy was 20% (14 of 70) in group 1 and 18.5% (13 of 70) in group 2. We found no cancer at the second biopsy in cases of PSA reduction below 4 ng/mL in both groups. Our protocol was very effective and safe in reducing PSA levels. The second biopsy failed to show prostate cancer in all patients with PSA lower than 4 ng/mL.

Is there any association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer?

ABSTRACTPurposeWe investigated the association between National Institute of Health category IV prostatitis and prostate-specific antigen levels in patients with low-risk localized prostate cancer.Materials and MethodsThe data of 440 patients who had undergone prostate biopsies due to high PSA levels and suspicious digital rectal examination findings were reviewed retrospectively. The patients were divided into two groups based on the presence of accompanying NIH IV prostatitis. The exclusion criteria were as follows: Gleason score>6, PSA level>20ng/mL, >2 positive cores, >50% cancerous tissue per biopsy, urinary tract infection, urological interventions at least 1 week previously (cystoscopy, urethral catheterization, or similar procedure), history of prostate biopsy, and history of androgen or 5-alpha reductase use. All patient's age, total PSA and free PSA levels, ratio of free to total PSA, PSA density and prostate volume were recorded.ResultsIn total, 101 patients were included in the study. Histopathological examination revealed only PCa in 78 (77.2%) patients and PCa+NIH IV prostatitis in 23 (22.7%) patients. The median total PSA level was 7.4 (3.5–20.0) ng/mL in the PCa+NIH IV prostatitis group and 6.5 (0.6–20.0) ng/mL in the PCa group (p=0.67). The PSA level was≤10ng/mL in 60 (76.9%) patients in the PCa group and in 16 (69.6%) patients in the PCa+NIH IV prostatitis group (p=0.32).ConclusionsOur study showed no statistically significant difference in PSA levels between patients with and without NIH IV prostatitis accompanying PCa.

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 μg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume.

The impact of hypoxemia on serum total and free prostate-specific antigen levels in patients with chronic obstructive pulmonary disease.

Prostate-specific antigen (PSA) is the most important biochemical marker in the diagnosis and follow-up of patients with prostate cancer. In recent years, a relationship between PSA levels and hypoxic conditions has been described. However, no study has investigated the PSA levels in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the impact of hypoxemia on serum total (tPSA) and free PSA (fPSA) levels in patients with COPD. Between January 2010 and January 2014, 95 male patients who hospitalized for acute exacerbations of COPD and 80 control subjects were enrolled in the study. Serum tPSA and fPSA levels and f/tPSA ratios were determined in all patients on the first day of hospitalization (exacerbation) and 7 days after the treatment (stable state). Statistical analysis included paired t test and Mann-Whitney U test. No statistically significant differences were found between COPD and control groups with regard to the baseline characteristics, except for smoking status. The levels of serum tPSA and fPSA during exacerbation of COPD were significantly higher than the levels of the stable period (p < 0.01), whereas f/tPSA ratio did not change (p > 0.05). Hypoxemia during acute exacerbation of COPD can cause a rise in serum tPSA and fPSA levels, but f/tPSA ratio is not affected. Acute exacerbation of COPD may be added to list of the events in which PSA measurements must be interpreted with caution.

Complete Biochemical (Prostate-specific Antigen) Response to Sipuleucel-T With Enzalutamide in Castration-resistant Prostate Cancer: A Case Report With Implications for Future Research

To describe the case of a patient with castration-resistant, metastatic prostate cancer who achieved a complete and durable biochemical response after treatment with sipuleucel-T while continuing with enzalutamide and to explore the immunologic basis for such a response. We obtained serial prostate-specific antigen (PSA) measurements and bone scans to assess the patient's response to enzalutamide followed by the addition of sipuleucel-T. Using preclinical and clinical data, we describe his response through known immunobiologic mechanisms. This patient's PSA level became undetectable during treatment with enzalutamide and began to increase again after 14 months. He opted for treatment with sipuleucel-T, while continuing with the enzalutamide. This resulted in another complete PSA response 6 months after exposure to sipuleucel-T. Sipuleucel-T typically does not produce significant PSA reductions, and, to the best of our knowledge, only 1 previous report of a durable complete PSA response in a patient with metastatic disease has been published. The timing of this response supports an immune mechanism. The biologic rationale for the combination, coupled with the clinical result observed in our patient, provides a basis for studies of the combination of sipuleucel-T and enzalutamide.

Balancing the harms and benefits of early detection of prostate cancer

van Leeuwen et al fail to explain why the prostate-specific antigen (PSA) by itself is misleading and how physicians can gather better data to achieve better outcomes with fewer side effects.1 A person may have a high prostate-specific antigen (PSA) level due to an enlarged prostate gland (which is quite common), irritation, inflammation, infection, or other changes of the prostate gland. Thus, a PSA level of 10 ng/mL may not necessarily require biopsies or aggressive therapy. I illustrate with 1 example so physicians will have a better view of likely noncancer variability (a subject that in my opinion is poorly understood and omitted in most studies). For over 5 years, patient PP had a PSA level between 9 and 11 ng/mL. He had a negative biopsy the first time his PSA level was found to be elevated. His prostate gland was substantially enlarged (but no exact measures were available), with the usual consequences. One day his PSA level was 21 ng/mL. The patient changed his diet and behavior drastically (losing weight, exercising more, eating healthier foods, and other behaviors). Within a few weeks, the PSA level declined to 15 and then 11 ng/mL. For the past 3 years, the patient's PSA level has remained between 9 and 11 ng/mL. When the PSA level was highly elevated, 1 of the top prostate cancer experts in the United States insisted that a biopsy be performed immediately, without waiting for repeated testing or the effects of the drastic diet and behavior changes proposed by the patient. The patient refused a biopsy. Physical examination of the prostate for the past 3 years has found no nodules. After having a PSA level of 10 ng/mL for >10 years, and 3 years after having a PSA level > 20 ng/mL, no cancer has been detected to date. PSA values of approximately 10 ng/mL are not necessarily indicative of a high probability of cancer, nor deserve biopsies. Although the relevant factors are not known, it is possible for a 10-point variation in PSA to be the result of factors other than cancer, which are correctable via diet, behavior modification, antibiotics (for infections), and other treatment models (different from cancer treatment). We need far better data regarding the probability of cancer given PSA level, prostate size, body size, prostate status (inflamed, infected, irritated, etc), types of diet, and other factors. We also need a probability distribution of the variability of PSA values over relatively short time periods (measured in months). In the interim, physicians should carefully evaluate the patient and consider alternative treatments (such as substantial weight loss and a healthier diet) before proceeding with a biopsy. Biopsies do have undesirable side effects, and could lead to unnecessary treatment, again with undesirable side effects. Eduardo Siguel MD, PhD*, * Gaithersburg, Maryland.

Poster 354: Prostate-Specific Antigen Levels in Patients with Chronic Spinal Cord Injury

Poster 354: Prostate-Specific Antigen Levels in Patients with Chronic Spinal Cord Injury

Preliminary Results of Radiation Therapy for Prostate Cancer in Human Immunodeficiency Virus–Positive Patients

The purpose of this study was to report on the clinical outcomes of patients treated at our institution for prostate cancer (PCa) who had been previously diagnosed as Human immunodeficiency virus (HIV) positive. The authors conducted a retrospective study of 14 PCa/HIV patients who were being treated for PCa with external beam radiotherapy, brachytherapy, or a combination of the two. Each patient's prostate-specific antigen (PSA) level, CD4 count, and viral load were obtained before the initial radiation treatment and at the time of their most recent follow-up. In addition, 13 of 14 patients completed a quality of life survey with a social worker on staff and were examined by their radiation oncologist to assess the complications after treatment. Comparing pretreatment data with the data at last follow-up, only 1 patient's PSA level remained above 1.1 ng/mL. The average CD4 count remained stable, increasing from 523 to 577 cells/mm(3), with the lowest final count at 200 cells/mm(3). Viral load increased in only 2 of 14 patients. There were no unusual rectal, urinary, or sexual complications, and no infections related to treatment. Based on changes in viral load and CD4 count, radiotherapy does not appear to have a long-term negative effect on the immune system. Treatment complications are consistent with HIV-negative patients, giving no evidence that the subset of PCa/HIV patients should be treated differently from PCa patients without HIV when considering radiation therapy. More investigation will be necessary before reliable mortality and morbidity data can be assessed.

The current status of intermittent androgen deprivation (IAD) therapy for prostate cancer: putting IAD under the spotlight

Intermittent androgen deprivation (IAD) is one approach to hormonal therapy for prostate cancer that has been developed with the aim of minimizing the negative effects of therapy while maximizing the clinical benefits and the patient's quality of life (QoL). It can be used in any clinical situation where continuous AD (CAD) treatment could be applied. IAD is a cyclic therapy consisting of on-treatment periods followed by observation periods, known as off-treatment periods or intervals (OTIs), and the response to therapy, or occurrence of disease progression, is monitored by measuring the patient's prostate-specific antigen (PSA) levels. The on-treatment period is generally fixed, normally lasting for 6-9 months or in some protocols until a PSA nadir of <4 ng/mL is reached. By contrast, the OTI is variable and treatment is re-instituted depending on the patient's PSA level; however, the exact trigger point is chosen empirically. The potential advantages of IAD over CAD therapy are an improved QoL, a prolonged period of androgen dependence, a reduced incidence of the side-effects normally associated with AD therapy, and a decrease in the cost of care. Results from phase II clinical studies of IAD have shown that it has good acceptance and feasibility. QoL improves during the OTIs, there is reduced toxicity, and a positive affect on bone density compared with CAD therapy. In these studies IAD appeared to have no negative effects on time to progression or survival. Further investigations of IAD are ongoing in randomized, controlled, phase III trials in the USA, Canada and Europe. Most of these studies are not yet mature and final results are awaited; however, interim analyses from some studies suggest IAD and CAD therapy are equally effective in terms of progression-free survival.