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European Urology Focus Jun 2024Pathological features in non-muscle-invasive bladder cancer specimens are pivotal in determining correct patients' therapeutic management. Sparse data exist regarding...
BACKGROUND AND OBJECTIVE
Pathological features in non-muscle-invasive bladder cancer specimens are pivotal in determining correct patients' therapeutic management. Sparse data exist regarding the importance of second opinion performed by an expert uropathologist. This study aimed to assess the importance of a second opinion by an expert uropathologist in the management of bladder cancer.
METHODS
The study relied on 272 bladder cancer specimens from 231 patients seeking a pathology second opinion after transurethral resection of the bladder for a clinical suspicion of bladder cancer, relapse, or second-look procedure. Pathology second opinion was offered by an experienced fellowship-trained uropathologist. Discrepancies were recorded considering primary tumor staging, the presence of muscularis propria, and the presence of histological variants. Cases were categorized as no significant discordance, major discordance without management change, and major discordance with management change according to the European Urology Association (EAU) guidelines.
KEY FINDINGS AND LIMITATIONS
Among 272 second opinion cases, 39% (108/272) had major discordance and 28% (75/272) had major discordance with change in management according to the EAU guidelines. Upstaging and downstaging were reported in 66 (24%) patients. Improper identification of the presence of muscularis propria was found in 46 (17%) cases, of which 11 (4%) were deemed clinically relevant. Differences regarding the presence of histological variants were diagnosed in 40 cases (15%), resulting in eight (3%) changes in clinical management. In ten specimens (4%), multiple clinically relevant discrepancies were found.
CONCLUSIONS AND CLINICAL IMPLICATIONS
The second opinion evaluation changed the clinical management in 25% of the cases. These results support the importance of specimen review by an expert uropathologist as a major driver in the correct bladder cancer management.
PATIENT SUMMARY
We investigated the importance of a second opinion performed by an expert uropathologist in the management of bladder cancer. We found that 25% had their treatment plan changed due to the revised pathological report.
PubMed: 38937195
DOI: 10.1016/j.euf.2024.06.007 -
Seminars in Oncology May 2024We examined data from US Veterans with prostate cancer (PC) to assess disease response to immune checkpoint inhibitors (ICI) as monotherapy or combined with abiraterone...
We examined data from US Veterans with prostate cancer (PC) to assess disease response to immune checkpoint inhibitors (ICI) as monotherapy or combined with abiraterone or enzalutamide to assess ICI efficacy in the real-world. We queried the VA corporate data warehouse (CDW) to identify Veterans with a diagnosis of PC who received ICI for any malignancy and had ≥1 PSA measurement while receiving ICI. To evaluate ICI monotherapy, we restricted analysis to Veterans who had not received LHRH agonists/antagonists, PC-directed medical therapy, or radiation/extirpative surgery of the bladder/prostate within and preceding the duration of ICI administration. For ICI combination analysis, we identified Veterans who received abiraterone or enzalutamide for PC while on ICI. We calculated rates of tumor (PSA) growth (g-rates), comparing them to a 1:2 matched reference cohort. We identified 787 Veterans with PC and ≥1 PSA measurement while receiving an ICI. Median duration of ICI therapy was 155 days. 223 Veterans received ICI monotherapy, with only 17(8%) having a reduction in PSA (median decline = 43%). 12 (5%) had PSA declines >30% (PSA30) which included 6 (3%) who had PSA reductions greater than 50% (PSA50). Median g-rates for ICI plus abiraterone (n = 20) or enzalutamide (n = 31) were 0.000689/d and 0.002819/d, respectively, and were statistically insignificant compared to g-rates of matched cohorts receiving abiraterone (g = 0.000925/d, P = 0.73) or enzalutamide (g = 0.001929/d, P = 0.58) alone. Our data align with clinical trial data in PC, demonstrating limited benefit from ICI monotherapy and predicting no survival benefit from simultaneous abiraterone or enzalutamide with an ICI using g-rate.
PubMed: 38937152
DOI: 10.1053/j.seminoncol.2024.04.002 -
Zhonghua Wai Ke Za Zhi [Chinese Journal... Jun 2024The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular...
The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (73.2%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the gene.
PubMed: 38937132
DOI: 10.3760/cma.j.cn112139-20240102-00002 -
Journal of Nuclear Medicine : Official... Jun 2024Homeobox 13 (HOXB13) is an oncogenic transcription factor that directly regulates expression of folate hydrolase 1, which encodes prostate-specific membrane antigen...
Homeobox 13 (HOXB13) is an oncogenic transcription factor that directly regulates expression of folate hydrolase 1, which encodes prostate-specific membrane antigen (PSMA). HOXB13 is expressed in primary and metastatic prostate cancers (PCs) and promotes androgen-independent PC growth. Since HOXB13 promotes resistance to androgen receptor (AR)-targeted therapies and regulates the expression of folate hydrolase 1, we investigated whether SUVs on PSMA PET would correlate with HOXB13 expression. We analyzed 2 independent PC patient cohorts who underwent PSMA PET/CT for initial staging or for biochemical recurrence. In the discovery cohort, we examined the relationship between HOXB13, PSMA, and AR messenger RNA (mRNA) expression in prostate biopsy specimens from 179 patients who underwent PSMA PET/CT with F-piflufolastat. In the validation cohort, we confirmed the relationship between HOXB13, PSMA, and AR by comparing protein expression in prostatectomy and lymph node (LN) sections from 19 patients enrolled in F-rhPSMA-7.3 PET clinical trials. Correlation and association analyses were also used to confirm the relationship between the markers, LN positivity, and PSMA PET SUVs. We observed a significant correlation between PSMA and HOXB13 mRNA ( < 0.01). The association between HOXB13 and F-piflufolastat SUVs was also significant (SUV, = 0.0005; SUV, = 0.0006). Likewise, the PSMA SUV was significantly associated with the expression of HOXB13 protein in the F-rhPSMA-7.3 PET cohort ( = 0.008). Treatment-naïve patients with LN metastases demonstrated elevated HOXB13 and PSMA levels in their tumors as well as higher PSMA tracer uptake and low AR expression. Our findings demonstrate that HOXB13 correlates with PSMA expression and PSMA PET SUVs at the mRNA and protein levels. Our study suggests that the PSMA PET findings may reflect oncogenic HOXB13 transcriptional activity in PC, thus potentially serving as an imaging biomarker for more aggressive disease.
PubMed: 38936974
DOI: 10.2967/jnumed.123.267301 -
In Vivo (Athens, Greece) 2024This study investigated the follow-up rate of living kidney donors and explored the factors related to continuous follow-up and remnant renal function, enabling the...
BACKGROUND/AIM
This study investigated the follow-up rate of living kidney donors and explored the factors related to continuous follow-up and remnant renal function, enabling the optimal management of living kidney donors.
PATIENTS AND METHODS
We retrospectively evaluated 180 living kidney donors who underwent donor nephrectomies at our institute. Clinical information was obtained from medical charts, and remnant renal function was defined as the estimated glomerular filtration rate 12 months after donor nephrectomy.
RESULTS
Overall, 6/180 donors (3.3%) were lost to follow-up within a year, and the follow-up rate gradually declined yearly. Independent risk factors for loss to follow-up included a follow-up period <60 months and graft survival of the recipient (p=0.002 and p=0.043, respectively). Recipient survival was correlated with loss to follow-up; however, this was not significant (p=0.051). Regarding remnant renal function, age ≥60 years, preoperative estimated glomerular filtration rate <74 ml/min/1.73 m, and a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73m were independent risk factors for poorly preserved remnant renal function (p=0.036, p<0.0001, and p<0.0001, respectively). Using propensity score matching to adjust for preoperative factors, a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73 m was the only significant postoperative factor for poorly preserved remnant renal function (p=0.023).
CONCLUSION
An increased 5-year follow-up rate could lead to an increase in long-term follow-up, and recipient prognosis may be correlated with the living kidney donor follow-up status. Furthermore, Δsingle-kidney estimated glomerular filtration rate was identified as a factor for establishing the optimal precision follow-up management of living kidney donors.
Topics: Humans; Living Donors; Nephrectomy; Male; Female; Middle Aged; Kidney Transplantation; Adult; Glomerular Filtration Rate; Follow-Up Studies; Risk Factors; Kidney; Retrospective Studies; Graft Survival; Postoperative Period; Kidney Function Tests; Aged
PubMed: 38936934
DOI: 10.21873/invivo.13645 -
In Vivo (Athens, Greece) 2024When hormone therapy (HT) is combined with radiotherapy, understanding the recovery of testosterone levels after the end of HT becomes crucial for considering subsequent...
BACKGROUND/AIM
When hormone therapy (HT) is combined with radiotherapy, understanding the recovery of testosterone levels after the end of HT becomes crucial for considering subsequent therapy. The aim of this study was to determine the factors influencing the time to recovery of testosterone levels after discontinuation of HT and the likelihood of recovery.
PATIENTS AND METHODS
The study included a total of 108 patients with prostate cancer who were treated with GnRH agonist in combination with radiotherapy and followed up for at least 12 months after discontinuation of the GnRH agonist. The presence of recovery of testosterone levels and the time to recovery were investigated. Univariate and multivariate analyses were performed on several factors contributing to testosterone recovery, including age at initiation of HT, and the duration of HT.
RESULTS
Testosterone levels recovered in 61 cases (56.5%). The median time to recovery was 14.8 months. There was a significant difference in the recovery of testosterone levels between patients aged ≥71 years and those aged <71 years at the start of HT (p=0.002), and between those who had been on HT for ≥34 months and those for <34 months (p=0.031). In both univariate and multivariate analyses, age at initiation of HT and duration of HT contributed to the recovery of testosterone levels.
CONCLUSION
The rate of recovery of testosterone levels after long-term (median 34.3 months) HT was lower in patients who were older than 71 years at the start of HT.
Topics: Humans; Testosterone; Male; Aged; Prostatic Neoplasms; Middle Aged; Aged, 80 and over; Gonadotropin-Releasing Hormone; Combined Modality Therapy; Treatment Outcome; Antineoplastic Agents, Hormonal
PubMed: 38936898
DOI: 10.21873/invivo.13666 -
Sexual Medicine Reviews Jun 2024One of the changes caused by pelvic cancers is the decrease in patients' sexual function, which influences their quality of life (QoL) during and after treatment. Sexual...
INTRODUCTION
One of the changes caused by pelvic cancers is the decrease in patients' sexual function, which influences their quality of life (QoL) during and after treatment. Sexual dysfunction (SD) is associated with severe ejaculatory dysfunction, sexual dissatisfaction, reduced libido and sexual desire, decreased intensity of orgasm, difficulty in erection, and lower sexual frequency.
OBJECTIVES
This systematic review investigated the effectiveness of conservative treatments (nonsurgical and nonpharmacologic) for SD in males with pelvic cancer.
METHODS
Systematic searches were performed in the Cochrane Library, PubMed, CINAHL, PEDro, Embase, and VHL databases in September 2023 by using MeSH terms related to population, study design, intervention, and outcome.
RESULTS
Only prostate cancer studies were included due to a lack of studies in other treatments. Studies used pelvic floor muscle training (8 studies); biofeedback (1 study); a penile vibrator (1 study); electrostimulation (2 studies); shock wave therapy (2 studies); aerobic, resistance, and flexibility exercises (2 studies); and a vacuum erection device (1 study). All articles assessed sexual function and reported improvements in the intervention group, including 5 with no differences between the groups. Articles involving shock wave therapy described improvements in SD but were not clinically relevant. Studies evaluating QoL reported benefits in the experimental groups. Adverse effects of a vacuum erection device and penile vibrator were reported.
CONCLUSION
Conservative treatments are more effective than others in treating SD in men with prostate cancer. Further studies are needed to assess the unwanted effects of these treatments. In this study, we found evidence that this type of therapy improves sexual function and QoL in this population.
PubMed: 38936816
DOI: 10.1093/sxmrev/qeae045 -
Urology Jun 2024To examine post-operative urinary and sexual functional outcomes for men with high-risk prostate cancer (HRPCa) who underwent radical prostatectomy (RP) within the...
OBJECTIVES
To examine post-operative urinary and sexual functional outcomes for men with high-risk prostate cancer (HRPCa) who underwent radical prostatectomy (RP) within the Michigan Urological Surgery Improvement Collaborative (MUSIC).
METHODS
We identified patients who underwent RP for HRPCa in MUSIC between 2014-2023. HRPCa was defined according to American Urological Association criteria. Patients completed Expanded Prostate Cancer Index Composite (EPIC-26) pre-RP and 3-, 6-, 12-, and 24-months postoperatively. Primary outcomes included social continence, defined as 0-1 pads used daily; and recovery of sexual function, defined as the ability to achieve erections firm enough for intercourse. Multivariable and bivariate analyses were performed to identify factors associated with recovery of social continence and sexual function.
RESULTS
1323 patients were included in the post-RP urinary continence analysis and 422 men in the sexual function analysis. 58% and 86% of patients achieved social continence at 3- and 12-months post-RP, respectively. Continence recovery was associated with higher baseline EPIC-26 urinary continence scores (OR 1.10, per 5 points, 95% CI 1.06-1.15, p<0.001), and negatively associated with increasing age (OR 0.78 per 5-year increase, 95% CI 0.71-0.85 p<0.001). 15% of patients had recovery of sexual function at 12-months post-RP. On bivariate analysis, recovery of sexual function was associated with nerve-sparing at time of RP, lower pre-operative PSA, and not receiving post-RP ADT/RT.
CONCLUSIONS
RP for HRPCa has acceptable rates of postoperative social continence. However, post-RP recovery of sexual function remains a challenge. This information has important implications for pre-operative counseling and post-operative follow-up for patients with HRPCa.
PubMed: 38936624
DOI: 10.1016/j.urology.2024.06.018 -
The Lancet. Oncology Jul 2024
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Antineoplastic Combined Chemotherapy Protocols; Androgen Antagonists; Neoplasm Metastasis; Treatment Outcome; Androgen Receptor Antagonists
PubMed: 38936382
DOI: 10.1016/S1470-2045(24)00335-8 -
JCO Precision Oncology Jun 2024Patients with hereditary cancer syndromes (HCS) have a high lifetime risk of developing cancer. Historically underserved populations have lower rates of genetic...
PURPOSE
Patients with hereditary cancer syndromes (HCS) have a high lifetime risk of developing cancer. Historically underserved populations have lower rates of genetic evaluation. We sought to characterize demographic factors that are associated with undergoing HCS evaluation in an urban safety-net patient population.
METHODS
All patients who met inclusion criteria for this study from 2016 to 2021 at an urban safety-net hospital were included in this analysis. Inclusion criteria were pathologically confirmed breast, ovarian/fallopian tube, colon, pancreatic, and prostate cancers. Patients also qualified for hereditary breast and ovarian cancers or Lynch syndrome on the basis of National Comprehensive Cancer Network guidelines. Institutional review board approval was obtained. Demographic and oncologic data were collected through retrospective chart review. Univariable and multivariable logistic regression models were constructed.
RESULTS
Of the 637 patients included, 40% underwent genetic testing. Variables associated with receiving genetic testing on univariable analysis included patients living at the time of data collection, female sex, Latinx ethnicity, Spanish language, family history of cancer, and referral for genetic testing. Patients identifying as Black, having Medicare, having pancreatic or prostate cancer, having stage IV disease, having Eastern Cooperative Oncology Group (ECOG) prognostic score ≥1, having medium or high Charlson comorbidity index, with current or previous cigarette use, and with previous alcohol use were negatively associated with testing. On multivariable modeling, family history of cancer was positively associated with testing. Patients identifying as Black, having colon or prostate cancer, and having ECOG score of 2 had significantly lower association with genetic testing.
CONCLUSION
Uptake of HCS was lower in patients identifying as Black, those with colon or prostate cancer, and those with an ECOG score of 2. Efforts to increase HCS testing in these patients will be important to advance equitable cancer care.
Topics: Humans; Female; Male; Safety-net Providers; Middle Aged; Retrospective Studies; Aged; Early Detection of Cancer; Hospitals, Urban; Adult; Genetic Testing; Neoplastic Syndromes, Hereditary
PubMed: 38935898
DOI: 10.1200/PO.23.00699