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Oncology (Williston Park, N.Y.) Aug 1996Pretreatment prostate-specific antigen (PSA) level is the single most important prognostic factor for patients undergoing radiotherapy for clinically localized prostate... (Review)
Review
Pretreatment prostate-specific antigen (PSA) level is the single most important prognostic factor for patients undergoing radiotherapy for clinically localized prostate cancer. When combined with Gleason score and T-stage, pretreatment PSA enhances our ability to accurately predict pathologic stage. Patients with pretreatment PSA levels > 10 ng/mL are at high risk for biochemical failure when treated with conventional radiation alone. A PSA nadir of > 1 ng/mL and a post-treatment PSA > 1.5 ng/mL are associated with a high risk of biochemical failure. Postoperative radiotherapy delivered while the tumor burden is low (eg, PSA < 1 ng/mL) predicts a favorable outcome. Many of these conclusions about the usefulness of pretreatment PSA are based on the assumption that PSA can be used as a surrogate end point for disease-free and overall survival from prostate cancer. However, this assumption still remains to be validated by phase III trials.
Topics: Antineoplastic Agents, Hormonal; Disease-Free Survival; Forecasting; Humans; Male; Neoplasm Staging; Polymerase Chain Reaction; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome
PubMed: 8869957
DOI: No ID Found -
Prostate Cancer and Prostatic Diseases Sep 2016Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound...
BACKGROUND
Treatment options for radio-recurrent prostate cancer are either androgen-deprivation therapy or salvage prostatectomy. Whole-gland high-intensity focussed ultrasound (HIFU) might have a role in this setting.
METHODS
An independent HIFU registry collated consecutive cases of HIFU. Between 2005 and 2012, we identified 50 men who underwent whole-gland HIFU following histological confirmation of localised disease following prior external beam radiotherapy (2005-2012). No upper threshold was applied for risk category, PSA or Gleason grade either at presentation or at the time of failure. Progression was defined as a composite with biochemical failure (Phoenix criteria (PSA>nadir+2 ng ml(-1))), start of systemic therapies or metastases.
RESULTS
Median age (interquartile range (IQR)), pretreatment PSA (IQR) and Gleason score (range) were 68 years (64-72), 5.9 ng ml(-1) (2.2-11.3) and 7 (6-9), respectively. Median follow-up was 64 months (49-84). In all, 24/50 (48%) avoided androgen-deprivation therapies. Also, a total of 28/50 (56%) achieved a PSA nadir <0.5 ng ml(-1), 15/50 (30%) had a nadir ⩾0.5 ng ml(-1) and 7/50 (14%) did not nadir (PSA non-responders). Actuarial 1, 3 and 5-year progression-free survival (PFS) was 72, 40 and 31%, respectively. Actuarial 1, 3 and 5-year overall survival (OS) was 100, 94 and 87%, respectively. When comparing patients with PSA nadir <0.5 ng ml(-1), nadir ⩾0.5 and non-responders, a statistically significant difference in PFS was seen (P<0.0001). Three-year PFS in each group was 57, 20 and 0%, respectively. Five-year OS was 96, 100 and 38%, respectively. Early in the learning curve, between 2005 and 2007, 3/50 (6%) developed a fistula. Intervention for bladder outlet obstruction was needed in 27/50 (54%). Patient-reported outcome measure questionnaires showed incontinence (any pad-use) as 8/26 (31%).
CONCLUSIONS
In our series of high-risk patients, in whom 30-50% may have micro-metastases, disease control rates were promising in PSA responders, however, with significant morbidity. Additionally, post-HIFU PSA nadir appears to be an important predictor for both progression and survival. Further research on focal salvage ablation in order to reduce toxicity while retaining disease control rates is required.
Topics: Aged; Combined Modality Therapy; Disease Progression; Follow-Up Studies; High-Intensity Focused Ultrasound Ablation; Humans; Male; Middle Aged; Multimodal Imaging; Neoplasm Grading; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Adjuvant; Survival Analysis; Treatment Outcome
PubMed: 27431499
DOI: 10.1038/pcan.2016.23 -
BMC Medical Research Methodology Sep 2022Prostate cancer is a very prevalent disease in men. Patients are monitored regularly during and after treatment with repeated assessment of prostate-specific antigen... (Review)
Review
BACKGROUND
Prostate cancer is a very prevalent disease in men. Patients are monitored regularly during and after treatment with repeated assessment of prostate-specific antigen (PSA) levels. Prognosis of localised prostate cancer is generally good after treatment, and the risk of having a recurrence is usually estimated based on factors measured at diagnosis. Incorporating PSA measurements over time in a dynamic prediction joint model enables updates of patients' risk as new information becomes available. We review joint model strategies that have been applied to model time-dependent PSA trajectories to predict time-to-event outcomes in localised prostate cancer.
METHODS
We identify articles that developed joint models for prediction of localised prostate cancer recurrence over the last two decades. We report, compare, and summarise the methodological approaches and applications that use joint modelling accounting for two processes: the longitudinal model (PSA), and the time-to-event process (clinical failure). The methods explored differ in how they specify the association between these two processes.
RESULTS
Twelve relevant articles were identified. A range of methodological frameworks were found, and we describe in detail shared-parameter joint models (9 of 12, 75%) and joint latent class models (3 of 12, 25%). Within each framework, these articles presented model development, estimation of dynamic predictions and model validations.
CONCLUSIONS
Each framework has its unique principles with corresponding advantages and differing interpretations. Regardless of the framework used, dynamic prediction models enable real-time prediction of individual patient prognosis. They utilise all available longitudinal information, in addition to baseline prognostic risk factors, and are superior to traditional baseline-only prediction models.
Topics: Humans; Male; Models, Statistical; Neoplasm Recurrence, Local; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 36123621
DOI: 10.1186/s12874-022-01709-3 -
Seminars in Arthritis and Rheumatism Aug 2017Psoriatic arthritis (PsA) is a heterogeneous inflammatory disorder that requires targeted treatment based on clinical manifestations, symptom severity, comorbidities,... (Review)
Review
OBJECTIVE
Psoriatic arthritis (PsA) is a heterogeneous inflammatory disorder that requires targeted treatment based on clinical manifestations, symptom severity, comorbidities, and other factors. Moderate or severe peripheral arthritis symptoms are typically treated with disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs (bDMARDs), and early and aggressive treatment is recommended in order to prevent permanent damage. Although rheumatologists are now able to choose between several bDMARDs for PsA that have different chemical structures, pharmacokinetic properties, dosing regimens, immunogenicity, safety profiles, and mechanisms of action, there is a lack of typical patient profiles or detailed treatment algorithms that can be followed when patients require alterations in their therapeutic regimens.
METHODS
PsA treatment recommendations were evaluated to identify consensus guidelines on switching between bDMARD therapies. PubMed literature searches were then conducted using the terms psoriatic arthritis, switch/switching, biologic, and TNF/tumor necrosis factor. Articles were deemed relevant if they presented data on switching between different bDMARDs in patients with PsA.
RESULTS
Data from the clinical literature on switching bDMARD therapies in PsA are limited. Evidence suggests that response to adalimumab, etanercept, and ustekinumab is lower after previous tumor necrosis factor inhibitor (TNFi) therapy and the efficacy of infliximab is independent of previous bDMARD treatment. Trials of ustekinumab and secukinumab showed efficacy responses were greater compared with placebo in patients who failed to respond to ≥1 TNFi.
CONCLUSION
Switching bDMARD therapies is a recommended strategy for patients who experience treatment failure. Many factors must be considered for determining which agent to switch to including PsA disease characteristics, comorbidities, cardiometabolic risk factors, treatment history, and patient preference. Switching between TNFis can be effective for many patients, but bDMARDs with different mechanisms of action may be superior alternatives.
Topics: Antibodies, Monoclonal; Antirheumatic Agents; Arthritis, Psoriatic; Biological Products; Cohort Studies; Disease Management; Drug Substitution; Drug Therapy, Combination; Female; Humans; Immunologic Factors; Longitudinal Studies; Male; Methotrexate; Observational Studies as Topic; Practice Guidelines as Topic; Severity of Illness Index; Tumor Necrosis Factor-alpha
PubMed: 28363434
DOI: 10.1016/j.semarthrit.2017.02.001 -
Contraception Nov 2019To investigate whether rates of self-reported Woman's Condom (WC) clinical failure and semen exposure from a functionality study are comparable to results from a... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To investigate whether rates of self-reported Woman's Condom (WC) clinical failure and semen exposure from a functionality study are comparable to results from a contraceptive efficacy substudy.
STUDY DESIGN
We structured our comparative analysis to assess whether functionality studies might credibly supplant contraceptive efficacy studies when evaluating new female condom products. Couples not at risk of pregnancy in the functionality (breakage/slippage/invagination/penile misdirection) study and women in the contraceptive efficacy study completed condom self-reports and collected precoital and postcoital vaginal samples for up to four uses of the WC. Both studies used nearly identical self-report questions and the same self-sampling procedures and laboratory for prostatic specific antigen (PSA), a well-studied semen biomarker. We compared condom failure and semen exposure proportions using generalized estimating equations methods accounting for within-couple correlation.
RESULTS
Ninety-five (95) efficacy substudy participants used 334 WC and 408 functionality participants used 1572 WC. Based on self-report, 19.2% WC (64 condoms) clinically failed in the efficacy substudy compared to 12.3% WC (194 condoms) in the functionality study (p=.03). Of the 207 WC efficacy uses with evaluable postcoital PSA levels, 14.5% (30 uses) resulted in semen exposure compared to 14.2% (184 uses) of the 1293 evaluable WC functionality study uses.
CONCLUSIONS
When evaluating the ability of an experimental condom to prevent semen exposure, the rate of clinical condom failure reported by participants risking pregnancy in an efficacy substudy was significantly higher than the rate reported by participants not risking pregnancy in a functionality study. The rate of semen exposure, assessed by an objective biomarker was nearly identical for the two studies.
IMPLICATIONS
Our results suggest that an objective marker of semen exposure in functionality studies could provide a reasonable alternative to contraceptive efficacy studies in evaluating risk of unintended pregnancy and inferring protection from sexually transmitted infection than condom failure rates based on self-report.
Topics: Adult; Condoms, Female; Contraceptive Effectiveness; Female; Humans; Male; Prostate-Specific Antigen; Self Report; Semen
PubMed: 31381878
DOI: 10.1016/j.contraception.2019.07.143 -
Cancer Medicine Dec 2019Although prostate-specific antigen (PSA) testing is used for prostate cancer detection and posttreatment surveillance, thresholds in these settings differ. The screening...
BACKGROUND
Although prostate-specific antigen (PSA) testing is used for prostate cancer detection and posttreatment surveillance, thresholds in these settings differ. The screening cutoff of 4.0 ng/mL may be inappropriately used during postsurgery surveillance, where 0.2 ng/mL is typically used, creating missed opportunities for effective salvage radiation treatment. We performed a study to determine whether guideline concordance with annual postoperative PSA surveillance increases when PSA values exceed 4 ng/mL, which represents a screening threshold that is not relevant after surgery.
METHODS
We used US Veterans Health Administration data to perform a retrospective longitudinal cohort study of men diagnosed with nonmetastatic prostate cancer from 2005 to 2008 who underwent radical prostatectomy. We used logistic regression to examine the association between postoperative PSA levels and receipt of an annual PSA test.
RESULTS
Among 10 400 men and 38 901 person-years of follow-up, annual guideline concordance decreased from 95% in year 1 to 79% in year 7. After adjustment, guideline concordance was lower for the youngest and oldest men, Black, and unmarried men. Guideline concordance significantly increased as PSA exceeded 4 ng/mL (adjusted odds ratio 2.20 PSA > 4-6 ng/mL vs PSA > 1-4 ng/mL, 95% confidence interval 1.20-4.03; P = .01).
CONCLUSIONS
Guideline concordance with prostate cancer surveillance increased when PSA values exceeded 4 ng/mL, suggesting a screening threshold not relevant after prostate cancer surgery, where 0.2 ng/mL is considered treatment failure, is impacting cancer surveillance quality. Clarification of PSA thresholds for early detection vs cancer surveillance, as well as emphasizing adherence for younger and Black men, appears warranted.
Topics: Aged; Biomarkers, Tumor; Guideline Adherence; Humans; Male; Mass Screening; Middle Aged; Models, Theoretical; Odds Ratio; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Public Health Surveillance; Treatment Outcome
PubMed: 31691526
DOI: 10.1002/cam4.2663 -
Rheumatology and Therapy Jun 2022Psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are chronic immune-mediated inflammatory diseases (IMIDs) associated with cardiovascular (CV)...
BACKGROUND
Psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are chronic immune-mediated inflammatory diseases (IMIDs) associated with cardiovascular (CV) disease. High-sensitivity C-reactive protein (hsCRP) and, more recently, the neutrophil-lymphocyte ratio (NLR) are important inflammatory biomarkers predictive of CV disease and CV disease-associated mortality. Here, we report the effect of interleukin (IL)-17A inhibition with secukinumab on CV risk parameters in patients with psoriasis, PsA, and axSpA over 1 year of treatment.
METHODS
This was a post hoc analysis of pooled data from phase 3/4 secukinumab studies in psoriasis, PsA, and axSpA. CV-related exclusion criteria included uncontrolled hypertension and congestive heart failure. Traditional risk factors assessed were body mass index (BMI) > 25, high fasting glucose and blood pressure (systolic and diastolic), and high cholesterol (low-density lipoproteins [LDL], total cholesterol/HDL ratio, and triglycerides). Inflammatory CV risk parameters assessed were hsCRP and NLR. Statistical analysis was descriptive. Subgroup analyses were performed in high-risk patients defined as having baseline hsCRP > 4 mg/L (patients with psoriasis) and > 10 mg/L (patients with PsA/axSpA).
RESULTS
In total, 9197 patients from 19 clinical trials (8 in psoriasis, n = 4742; 5 in PsA, n = 2475; 6 in axSpA, n = 1980) were included. All traditional CV risk parameters remained stable in secukinumab-treated patients through 1 year. Secukinumab rapidly reduced both hsCRP and the NLR compared with placebo at week 12 (psoriasis) or week 16 (PsA/axSpA) in the overall population and in high-risk patients (all P < 0.01). This reduction was maintained for at least 1 year of secukinumab therapy in all indications.
CONCLUSIONS
Secukinumab led to a rapid and sustained reduction in hsCRP and the NLR in patients with IMIDs with a high systemic inflammatory burden. Traditional CV risk factors remained stable for at least 1 year in patients with psoriasis, PsA, and axSpA. Taken together, secukinumab had a favorable effect on systemic inflammation without impact on traditional CV risk factors.
TRIALS REGISTRATION
ClinicalTrials.gov, NCT01365455, NCT01358578, NCT01406938, NCT01555125, NCT01636687, NCT02752776, NCT02074982, NCT02826603, NCT01752634, NCT01989468, NCT02294227, NCT02404350, NCT02745080, NCT01863732, NCT01649375, NCT02008916, NCT02159053, NCT02896127, NCT02696031.
PubMed: 35305260
DOI: 10.1007/s40744-022-00434-z -
Technology in Cancer Research &... 2021To assess the clinical outcomes of prostate cancer patients treated with salvage radiotherapy (SRT) for locoregional clinical recurrence (CR) after radical...
To assess the clinical outcomes of prostate cancer patients treated with salvage radiotherapy (SRT) for locoregional clinical recurrence (CR) after radical prostatectomy (RP). Records of 60 patients with macroscopic locoregional recurrence after prostatectomy and referrals for SRT were retrospectively investigated in the multi-institutional database. The median radiation dose was 70.2 Gy. Biochemical failure was defined as the prostate-specific antigen (PSA) ≥ nadir + 2 or initiation of androgen deprivation therapy (ADT) for increased PSA. Median recurrent tumor size was 1.1 cm and pre-radiotherapy PSA level was 0.4 ng/ml. At a median follow-up of 83.1-month after SRT, 7-year biochemical failure-free survival (BCFFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 67.0%, 89.7%, 83.6%, and 91.2%, respectively. Higher Gleason's scores were associated with unfavorable BCFFS, DMFS, and OS. Pre-SRT PSA ≥0.5 ng/ml predicted worse BCFFS, LRFFS, and DMFS. In multivariate analyses, a Gleason's score of 8 to 10 was associated with decreased BCFFS (hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.11-8.74, = .031) and OS (HR 17.72, 95% CI 1.75-179.64, = .015), and combined ADT decreased the risks of distant metastasis (HR 0.18, 95% CI 0.04-0.92, = .039). Two patients (3.3%) experienced late grade 3 urinary toxicity. SRT for locoregional CR after RP achieved favorable outcomes with acceptable long-term toxicities. Higher Gleason's scores and pre-radiotherapy PSA level were unfavorable prognostic variables. Combined ADT may decrease the risks of metastases.
Topics: Aged; Androgen Antagonists; Combined Modality Therapy; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Intensity-Modulated; Retrospective Studies; Salvage Therapy; Survival Rate
PubMed: 34806469
DOI: 10.1177/15330338211041212 -
Radiation Oncology (London, England) Aug 2023Oligometastatic disease in prostate cancer (PCa) is a challenging clinical scenario encountered more frequently with the widespread adoption of PSMA-PET. SBRT aims to...
BACKGROUND
Oligometastatic disease in prostate cancer (PCa) is a challenging clinical scenario encountered more frequently with the widespread adoption of PSMA-PET. SBRT aims to defer androgen deprivation and may deliver sustained biochemical failure (BF) free survival in selected patients. Little long-term data is currently available regarding the effectiveness of this approach.
METHODS
A retrospective single institution study of PSMA-PET directed SBRT without initial ADT for oligo-metachronous PCa. Median dose/fractionation was 24 Gy in 2# to bones and 30 Gy in 3# to lymph nodes. The primary endpoint was time to BF (PSA + 0.2 ug/L above nadir). Secondary endpoints included time to ADT for relapse (i.e. palliative ADT), BF defined as PSA nadir + 2 ug/L, toxicity, patterns of failure and survival. Patients were excluded if they received ADT with their SBRT, had short disease-free interval, or > 3 metastases on PSMA-PET.
RESULTS
103 patients treated from November-2014 to December-2019 were analysed from our prospective database. Median follow-up was 5 years. 64 patients were treated for nodal only disease, 35 bone only and 4 mixed. 15% were free of any BF at 5 years with median time to BF of 1.1 years. 32% (33/103) of patients had further curative-intent radiation treatment following their first BF after SBRT, including subsequent SBRT. Eight patients underwent potentially curative treatment for their second or third relapse. Allowing for salvage treatment, 29/103 (28%) were biochemically disease free at last follow up. At 5 years, 39% of patients had never received any ADT and 55% had not started ADT for relapse with a median time to ADT for relapse of 5.5 years. There were 2 grade 3 toxicities (rib fracture and lymphoedema), and no local failures.
CONCLUSION
PSMA-PET guided SBRT for oligo-metachronous PCa recurrence in appropriately triaged patients results in excellent local control, low toxicity and over 50% ADT free at 5 years.
Topics: Male; Humans; Prostatic Neoplasms; Treatment Outcome; Prostate-Specific Antigen; Androgen Antagonists; Retrospective Studies; Radiosurgery; Neoplasm Recurrence, Local; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography
PubMed: 37528487
DOI: 10.1186/s13014-023-02302-8 -
Rheumatology (Oxford, England) Jan 2015Rheumatologists have long considered OA and PsA as two completely distinct arthropathies. This review highlights how some forms of generalized OA and PsA may afflict the... (Comparative Study)
Comparative Study Review
Rheumatologists have long considered OA and PsA as two completely distinct arthropathies. This review highlights how some forms of generalized OA and PsA may afflict the same entheseal-associated anatomical territories. While degeneration or inflammation may be clearly discernible at the two extremes, there may be a group of patients where differentiation is impossible. Misdiagnosis of a primary degeneration-related pathology as being part of the PsA spectrum could lead to apparent failure of disease-modifying agents, including apparent anti-TNF and apparent IL23/17 axis therapy failure. This is not a reflection of poor clinical acumen, but rather a failure to appreciate that the pathological process overlaps in the two diseases. Whether the category of OA-PsA overlap disease exists or whether it represents the co-occurrence of two common arthropathies that afflict the same anatomical territories has implications for the optimal diagnosis and management of both OA and PsA.
Topics: Arthritis, Psoriatic; Biological Products; Diagnosis, Differential; Disease Management; Humans; Magnetic Resonance Imaging; Osteoarthritis; Phenotype; Rheumatic Diseases; Treatment Outcome
PubMed: 25231177
DOI: 10.1093/rheumatology/keu328