Seminal Vesicle Research Articles

Zinner’s Syndrome: Case report of a Developmental Anomaly of the Mesonephric Duct

Zinner’s syndrome is a rare congenital malformation characterized by the association of unilateral renal agenesis with ipsilateral seminal vesicle cyst and ejaculatory duct obstruction. Most patients are asymptomatic until the third or fourth decade of life when the syndrome is associated with dysuria, perineal pain, infertility, and painful ejaculation. In this report, we present the common imaging findings of this rare developmental anomaly involving the mesonephric duct in a 48-year-old male patient experiencing pelvic pain, recurrent dysuria, and pollakiuria.

Surgery with or Without Darolutamide in High-risk and/or Locally Advanced Prostate Cancer: The SUGAR (CCAFU-PR2) Phase 2 Trial Rationale and Protocol

BackgroundHigh-risk prostate cancer (PCa) patients frequently experience recurrence and progression after radical prostatectomy (RP). Neoadjuvant androgen deprivation therapy (ADT) has not demonstrated a clear oncological benefit and is not currently recommended. ObjectiveThe SUGAR trial is the first phase 2, randomised, controlled, multicentre, noncommercial, open-label study investigating single-agent perioperative darolutamide compared with the standard of care (ie, upfront RP, without neoadjuvant ADT). Design, setting, and participantsSUGAR aims to randomise 240 men affected by nonmetastatic PCa, with the major eligibility criteria being International Society of Urological Pathology grade group ≥4, seminal vesicle invasion at magnetic resonance imaging and/or clinically node-positive disease. Patients in the experimental arm will undergo neoadjuvant darolutamide monotherapy, RP, and adjuvant darolutamide, completing 9 mo of treatment. Outcome measurements and statistical analysisThe primary endpoint is noncurable recurrence-free survival, an innovative and clinically meaningful measure; the secondary endpoints encompass safety; recurrence-free, metastasis-free, and overall survival; pathological response; and quality of life. A predictive biomarker analysis will also be performed. Results and limitationsInitial data suggest that intensified neoadjuvant treatment with androgen receptor signalling inhibitors (ARSIs) is associated with a sustained pathological response and may improve outcomes, via tumour downstaging and micrometastasis eradication. ARSI monotherapy could further enhance tolerability. ConclusionsSUGAR will provide efficacy and safety information on perioperative darolutamide monotherapy compared with upfront RP, in a contemporary high-risk PCa population undergoing surgery. Patient summaryThe on-going SUGAR clinical trial evaluates 9 mo of darolutamide treatment in addition to radical prostatectomy, in men affected by prostate cancer with specific high-risk characteristics. It investigates whether this hormonal treatment can lower the rates of noncurable recurrences, maintaining a favourable tolerability profile.

FRI445 A Late Diagnosis Of Complete Androgen Insensitivity Syndrome

Abstract Disclosure: J. Muuse: None. R.J. Shah: None. P.A. Belany: None. Introduction: Complete Androgen Insensitivity Syndrome (CAIS) is a rare disorder of hormone resistance characterized by a female phenotype in an individual with an XY karyotype. Individuals with CAIS are born unambiguously female without any apparent abnormalities. They develop a short blind ending vaginal canal, with absence of Wolffian duct derived structures (vas deferens, seminal vesicles). Breast development advances regularly at puberty, while there is absent pubic and axillary hair, both due to peripheral conversion of testosterone to estrogen. Testes remain undescended in the abdominal cavity. Case: A 28 year old female with a past medical history of bipolar disorder presented to her primary care physician’s office with a chief complaint of fatigue. Blood work revealed an elevated testosterone level of 686, at which time she was referred to endocrinology for further work up. On further history gathering, she endorsed a life long history of amenorrhea. She saw an OB-GYN at 19 years old and was told she had a short vaginal canal. A pelvic ultrasound revealed no uterus and one left ovary. She was not given a diagnosis other than congenital absence of a uterus. She was lost to follow up until 28 years of age when she sought medical help for her fatigue. Physical exam was pertinent for a tall female with no signs of hirsuitism. Additional blood work revealed normal LH, FSH, and DHEA-S. A chromosomal analysis revealed XY. She was referred to gynecology for further management and assessment for orchiectomy. Discussion: This was an unusual case of CAIS, as this was diagnosed far past menarche. Most cases are diagnosed during puberty- which aids in an early approach towards the psychological and social well being of the individual as well as close follow up for evaluation of orchiectomy. Orchiectomy is recommended due to the increased risk of gonadal malignancy following puberty. The risk of developing malignancy increases with age, and has been reported to be between 15-22%. Thus it is important to identify this syndrome early in life to ensure this is addressed. It is followed by long term hormonal therapy with estrogen to maintain normal breast and bone development. This case highlights the importance of maintaining a high clinical suspicion of CAIS in females presenting with short vaginal canal and absence of a uterus in order to prevent malignancy and provide optimal psychological support to the individual. Presentation: Friday, June 16, 2023

Long- and short-read RNA sequencing from five reproductive organs of boar

The production of semen in boars involves multiple reproductive glands, including the testis (Tes), epididymis (Epi), vesicular gland (VG), prostate gland (PG), and bulbourethral gland (BG). However, previous studies on boar reproduction primarily focused on the testis, with little attention paid to the other glands. Here, we integrated single-molecule long-read sequencing with short-read sequencing to characterize the RNA landscape from five glands of Banna mini-pig inbred line (BMI) and Diannan small-ear pigs (DSE). We identified 110,996 full-length isoforms from 22,298 genes, and classified the alternative splicing (AS) events in these five glands. Transcriptome-wide variation analysis indicated that the number of single nucleotide polymorphisms (SNPs) in five tissues of BMI was significantly lower than that in the non-inbred pig, DSE, revealing the effect of inbreeding on BMI. Additionally, we performed small-RNA sequencing and identified 299 novel miRNAs across all glands. Overall, our findings provide a comprehensive overview of the RNA landscape within these five glands, paving the path for future investigations on reproductive biology and the impact of inbreeding on pig transcriptome.

Diagnostic Performance of PSMA-Based 18F-DCFPyL PET/CT in Prostate Cancer Patients After Definitive Treatment With PSA Level ≤0.2 ng/mL.

The aim of this study was to investigate the role of 18F-DCFPyL PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment and with low-level prostate-specific antigen (PSA) level of ≤0.2 ng/mL. This retrospective study was conducted in PC patients who received definitive treatments with PSA level of ≤0.2 ng/mL and underwent 18F-DCFPyL PET/CT within a 1-week interval of PSA examination, and without interval treatment change or history of other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on 18F-DCFPyL PET/CT were collected. Patients with minimal 6-month (median, 11 months; range, 6-21 months) follow-up or definitive biopsy results of the suspected PET/CT findings were included. Imagine findings were reached with consensus among experienced board-certified nuclear medicine physicians. Comprehensive follow-up and/or biopsy results were used as definitive determination of presence or absence of disease. Comparisons between groups of positive and negative 18F-DCFPyL PET/CT were done by using descriptive statistics. A total of 96 18F-DCFPyL PET/CTs from 93 patients met the inclusion criteria. The median Gleason score (GS) of positive group is 8 (range, 6-10), whereas negative group is 7 (range, 6-10). The median age of positive group is 71 (range, 50-90), whereas negative group is 69 (range, 45-88). There were 49 positive (51%) and 47 negative 18F-DCFPyL PET/CTs (49%). Detection rates at PSA level of ≤0.1 and 0.2 ng/mL were 58.7% (27/46) and 44% (22/50), respectively. The scan-based sensitivity, specificity, positive predictive value, and negative predictive value are 100%, 95%, 96%, and 100% in group with PSA level of ≤0.1 ng/mL, and 100%, 97%, 95%, and 100% in group with PSA level of 0.2 ng/mL, respectively. Sites of involvement on positive 18F-DCFPyL PET/CTs were prostate bed, pelvic lymph nodes, bone, chest and supraclavicular lymph nodes, lung, and adrenal glands. The SUVmax value on positive lesions ranged from 1.9 to 141.4; the smallest positive lymph node was 0.4 cm. High GS of 8-10, known metastatic status (M1), presence of extraprostatic extension, presence of seminal vesicle invasion, and very high-risk PC are significantly associated with positive 18F-DCFPyL PET/CT results (P < 0.05). Of all analyzed treatment regimes, upfront surgery (radical prostatectomy with or without pelvic lymph node dissection) had strong correlation with negative PET/CT results (P < 0.001). If patients received ADT only, or ADT plus chemotherapy, the PET/CT results were most likely positive (P = 0.026). For other treatment regimes, there were no statistical differences between the groups (P > 0.05). In the presence of low PSA level in PC patients after definitive treatment, 18F-DCFPyL PET/CT is most beneficial in detection of disease in patients with GS of 8 or higher at the time of diagnosis, and the ones who have history of ADT only, or ADT plus chemotherapy. There is excellent negative prediction value of 18F-DCFPyL PET/CT. However, there is no cutoff PSA level for 18F-DCFPyL PET/CT indication and no correlation between PSA level and SUVmax of positive lesions on 18F-DCFPyL PET/CT.

Kisspeptin treatment reverses high prolactin levels and improves gonadal function in hypothyroid male rats

We evaluated whether the administration of kisspeptin-10 (Kp10) is capable of restoring gonadal function in hypothyroid male rats. Hypothyroidism was induced with 6-propyl-2-thiouracil (PTU) for three months. In the last month, half of the hypothyroid animals were treated with Kp10. Hypothyroidism reduced testicular and sex gland mass, decreased the proliferation of the seminiferous epithelium, and compromised sperm morphology, motility, and vigor. A decrease in plasma LH and testosterone levels and an increase in prolactin secretion were observed in the hypothyroid rats. Hypothyroidism reduced Kiss1 and Kiss1r protein and gene expression and Star and Cyp11a1 mRNA levels in the testis. Furthermore, it reduced Lhb, Prl, and Drd2 and increased Tshb and Gnrhr expression in the pituitary. In the hypothalamus, hypothyroidism increased Pdyn and Kiss1r while reducing Gnrh1. Kp10 treatment in hypothyroid rats restored testicular and seminal vesicle morphology, improved sperm morphology and motility, reversed high prolactin levels, and increased LH and testosterone levels. In addition, Kp10 increased testicular expression of Kiss1, Kiss1r, Fshr, and Nr5a1 and pituitary Kiss1 expression. Our findings describe the inhibitory effects of hypothyroidism on the male gonadal axis and sperm quality and demonstrate that Kp10 treatment reverses high prolactin levels and improves gonadal function and sperm quality in hypothyroid rats.

Impact of forced diuresis at two different time points on pelvic imaging in prostatic carcinoma with 68Ga-PSMA PET/CT.

We compared diagnostic quality of 68Ga-PSMA PET/CT imaging focused on the pelvic structures using two furosemide protocols in two different groups of patients. A total of 55 patients with prostate cancer were retrospectively enrolled in the study. Out of 55, 31 patients were in group 1 (median age: 66 years, Range 44-78 years) in which furosemide injection was given after completion of whole-body 68Ga-PSMA PET/CT scan and 24 patients were in group 2 (median age: 63.5 years, range: 50-82 years) in which it was given along with the 68Ga-PSMA injection. In both groups, an initial time point scan (T0 scan) and a delayed time point scan (T1scan) were done. The images were analyzed qualitatively as well as quantitatively. Quantitatively there was no statistically significant difference between the SUVmax and T:B of prostatic lesion and seminal vesicle invasion (SVI) in both the groups at two time points (P > 0.05). Early furosemide injection caused a washout of the urinary bladder radiotracer concentration in significantly higher number of patients in group 2 (62.5% vs. 6.45% patients, P < 0.001). There was significant clearance of radiotracer activity from the ureters in group 2 (SUVmax: 9.28 vs. 3.09, P = 0.002). The simultaneous furosemide and 68Ga-PSMA injection can reduce the urinary excretion of the tracer and improve the diagnostic confidence of prostatic lesion, SVI and lymph nodal metastasis, along with reducing the scanning time and radiation burden, making this protocol an effective alternative to the present protocol of delayed furosemide injection.

Zinner's syndrome: clinical case of a rare pathology

Zinner’s syndrome is a rare congenital urogenital anomaly characterised by the triad of seminal vesicle cyst, ipsilateral renal aplasia, and seminal duct obstruction. According to the published data, the incidence of seminal vesicle cysts with ipsilateral renal agenesis is 0.0046%, but the true incidence appears to be higher. The article presents a rare clinical case of patient K, 17 years old, followed since birth with a solitary right kidney. The patient was repeatedly examined (ultrasound, cystography, urography, abdominal MRI, pelvic CT). The boy was admitted to our clinic with the diagnosis of "Solitary right kidney" and pelvic cystic formation detected according to the last CT scan. MRI examination of the small pelvis, cystoscopy, diagnostic laparoscopy, puncture of the cystic mass were performed. The diagnosis of "Zinner's syndrome" was made. The size of the cyst did not change during follow-up.

Long-term Overall Survival after External Beam Radiotherapy for Localised Prostate Cancer

AimsKnowledge on survival probabilities is essential for determining optimal treatment strategies. We studied overall survival and associated prognostic factors in Dutch patients with localised prostate cancer (PCa) selected for external beam radiotherapy. Materials and methodsFor this single-centre retrospective cohort study, we identified all T1-T3 PCa patients (aged 55–80 years) in the radiotherapy planning database with a start date between January 2006 and December 2013, treated with 72–78 Gy in 2 Gy fractions to the prostate ± seminal vesicles (n = 1536). Long-term androgen deprivation therapy (ADT) was predominantly prescribed in the case of extracapsular disease (>T3). Overall survival was estimated using the Kaplan–Meier method. Prognostic factors were evaluated in Cox regression models for the intermediate-risk and high-risk groups. ResultsThe median follow-up was 12 years for patients who were alive. Ten-year survival rates were 79.0% for low-risk (n = 120), 59.9% for intermediate-risk (n = 430) and 56.8% for high-risk patients (n = 986). A higher age, higher comorbidity score, active smoking and Gleason score ≥8 had a statistically significant negative impact on overall survival at multivariable analysis. ADT was associated with superior overall survival in the high-risk group translating into overall survival rates similar to the intermediate-risk group. ConclusionsAlthough PCa patients selected for external beam radiotherapy are typically in good health, their comorbidity score and smoking habits appeared to be dominant predictors for overall survival. Overall survival rates within the high-risk group varied, showing improved overall survival with ADT prescription and worse overall survival in the case of Gleason score ≥8.

Study of prostate-specific antigen levels during salvage radiotherapy after prostate cancer surgery

BackgroundAdministration of adjuvant or salvage radiotherapy (RT) after prostate cancer (PCa) surgery is supported by clinical evidence and is a widely adopted strategy. On occasion, we detect changes in prostate-specific antigen (PSA) levels, such as a transient elevation or decline, during RT. Thus, we retrospectively investigated the frequency of changes in PSA levels, their associations with histopathological parameters, PSA doubling time (PSADT), and biochemical recurrence (BR) of PCa.MethodsThis study included 23 consecutive patients who underwent surgery for PCa between 2012 and 2019, received salvage RT without hormone therapy, and exhibited changes in PSA levels during RT. The prostatic bed was irradiated with a total dose of 64 to 66 Gy. BR was defined as consecutive PSA levels exceeding 0.2 ng/mL or having to start hormone therapy because of PSA elevation after salvage RT.ResultsDuring salvage RT after PCa surgery, PSA levels transiently increased in 11 patients (47.8%) and decreased in 12 (52.2%). When factors associated with BR were examined in patients with transient PSA elevation, seminal vesicle invasion and preoperative PSA values were identified as being statistically significant. When factors for BR were examined in patients with a decline in PSA levels, the Gleason score and PSADT were identified as being significant. Among the cases of a decline in PSA levels during salvage RT, those who received a radiation dose of less than 36 Gy did not experience BR. Similarly, patients who exhibited changes in PSA levels during salvage RT and did not have perineural invasion did not experience BR.ConclusionThis is the first study to examine the histopathological factors possibly affecting BR in patients undergoing salvage RT after PCa surgery. The results indicate that in patients with transient PSA elevation, seminal vesicle invasion is a significant risk factor. On the other hand, in patients with a decline in PSA levels during irradiation, the Gleason score and perineural invasion were found to be potential risk factors for BR. These findings suggest that a thorough examination of postoperative histopathological results may be necessary for the optimal management of patients with PCa.

The effects of boar seminal plasma extracellular vesicles on sperm fertility

Extracellular vesicles (EVs) are abundant in body fluid and are critical in cell interaction. Seminal plasma contains numerous EVs which affecting sperm function via transferring regulatory cargoes to the sperm. However, the mechanism of seminal plasma extracellular vesicles (SP-EVs) is still not clear. The present study aimed to isolate the boar SP-EVs and explore its potential function, then identify the key protein involved in SP-EVs and sperms interaction, and elucidate mechanism of SP-EVs protein on sperms. Here, we successfully isolated and concentrated boar SP-EVs, the SP-EVs showed a typical vesicle structure under transmission electron microscopy, most of their diameters range between 50 and 200 nm and express EVs biomarkers CD9 and CD63. We proved that SP-EVs could inhibit sperm acrosome reaction and in vitro fertility. Through a data-independent acquisition analysis of protein profiles of noncapacitated sperms, normal capacitated sperms and SP-EVs treated capacitated sperms, we identified that EZRIN was one of the active proteins that participated in SP-EVs and sperms interaction. Furthermore, we tested that the inhibition of EZRIN could promote boar sperm fertility, which is in consistence with the function of SP-EVs. The results may facilitate future research of SP-EVs on sperm function and male infertility.

Clinical Evaluation of Deep Learning-Based Auto-Segmentation toward MRI-Only Prostate Radiotherapy.

Due to its superior soft-tissue contrast, MRI is the imaging modality of choice for target and organs-at-risk delineation in prostate radiotherapy. A recent advanced MR scanner allows for an MRI-only workflow owing to its ability to generate synthetic CT (MRCAT) that enables accurate dose calculation and treatment planning. While auto-segmentation algorithms for CT images are increasingly being adopted in clinical practice, there are fewer such algorithms for MRI images. The purpose of this study was to evaluate a deep learning-based auto-segmentation tool (from MVision AI) for both MRI and MRCAT images. We hypothesize that such algorithms could produce accurate contours that require little manual editing, resulting in significant time saving and workflow efficiency in MRI-only treatment planning. T2 MRI and MRCAT image pairs (acquired on a Philips Ingenia 1.5T MRI Scanner) for 10 prostate patients treated in an MRI-only workflow at our institution were retrospectively collected with IRB approval. These image volumes were then segmented using deep learning-based auto-segmentation models trained for MRI and CT images, respectively. The structures were manually edited by an experienced physician in a commercial imaging informatics system (Velocity). Finally, the auto-segmented and the post-edit structures were compared using Dice Similarity Coefficient (DSC) and 95% Hausdorff Distance (HD95). Excellent agreement was found between the auto-segmented and post-edit structures. For MRCAT, the average DSC was 0.92±0.03, 0.99±0.00, 0.90±0.06, 0.89±0.07, 0.89±0.06, 0.95±0.04, and 0.96±0.03 for prostate, bladder, rectum, penile bulb, seminal vesicles, left femur, and right femur, respectively. The average HD95 for these structures were 0.65±0.51mm, 0.01±0.01mm, 2.07±1.68mm, 1.10±0.91mm, 1.67±1.81mm, 0.86±1.24mm, and 0.67±1.49mm, respectively. For MRI, the average DSC was 0.96±0.02, 0.99 ±0.00, 0.96±0.03, 0.87±0.03, 0.94±0.06, and 0.89±0.11 for prostate, bladder, rectum, penile bulb, seminal vesicles, and Barrigel spacer, respectively. The average HD95 was 0.25±0.21mm, 0.00±0.00mm, 1.60±1.87mm, 1.43±0.98mm, 0.50±0.86mm, and 1.56±2.26mm, respectively. We evaluated the clinical acceptability of deep learning-based auto-segmentation models for prostate radiotherapy, one for MRI and one for MRCAT delineation. Both models demonstrated superior accuracy, and a high degree of consistency, offering the potential for significant time saving in treatment planning and improved workflow efficiency.

Location of Local Recurrences Post-Prostatectomy Detected by 18F-DCPFyL and Implications for Salvage Radiotherapy Target Volumes.

The use of prostate-specific membrane antigen (PSMA) PET scans have improved detection of recurrent prostate cancer for biochemical failure post-prostatectomy. The primary aim of this study is to assess the location of local recurrences for PSMA PET positive disease post-prostatectomy relative to anatomical landmarks and to inform salvage radiotherapy contouring guidelines. This is a retrospective study of patients who underwent a staging PSMA PET-CT scan with 18F-DCFPyL tracer. Eligible patients included men with biochemical recurrence (PSA >0.2ng/mL) post-prostatectomy for prostate adenocarcinoma. PSMA positive local disease (GTV) was marked on the CT scan of the PSMA PET/CT, using the PSMA PET scan fused as the secondary dataset. Reference structures were contoured to compare the positional relationship to the GTV local recurrence. Centroids of each GTV position were measured to the closest border of the reference structures and distance measured. Forty-five patients had a local recurrence on PSMA PET, 28/45 with prostate bed recurrence and 17/45 with seminal vesicle bed recurrence. The median age was 72.7 years, median pre-treatment PSA 0.515 ng/ml (0.2-11.1), pT2 in 37.8% and pT3 in 62.2, ISUP G2-3 was 66.7%, ISUP 4-5 29.6%, 67% ECE, 15.4% SV involvement and 40% positive margin. For prostate bed recurrences, 93.6% of GTVs were within 15mm from the inferior border of pubic symphysis (median 3.3mm [-9.8-15.4]), 83.9% within 10mm from the VUA (median 3.3mm [-17.4-15.9]), and 80.6% were greater than 10mm from the most superior slice of the penile bulb (median 16.4mm [1-29.5]). Laterally, 83.9% of recurrences were within 10mm of midline and 41.9% within 5mm (median 3.3mm [-13.56-11.59]) and all were contained within levator, 35.5% within 5mm (median 7.7 [1-22.6]) of the medial muscle border. 29.0% were within 5mm from the anterior edge of the rectal wall (median -7mm [-32.3-0.5]). Seminal vesicle bed recurrences were within 17.5mm of upper border of pubic symphysis for 88.9% of patients (median -4.69mm[-30.8to18.2]), 100% were more than 7.5mm inferiorly from the vas deferens (median-22.1mm[-32.7to-7.7]). Laterally, 100% recurrences were more than 7.5mm medial from obturator internus (median 5.37mm [-23.1to37.8]), and 88.9% were more than 10mm from midline (median 23.1mm [2.0-36.6]). The 18F-DCFPyL PSMA PET local recurrences can provide detailed localization of prostate bed and seminal vesicle recurrences. Our data can inform contouring guidelines for salvage radiotherapy to the prostate bed, particularly when using anatomical landmarks to define cranio-caudal extent of target volumes. For target volume laterally, the medial wall of levator ani would encompass all prostate bed recurrences, and no seminal vesicles recurrences were seen at the medial border of the obturator internus muscle.

Effects of Radiation Doses on Clinical Recurrence in Patients with Biochemically Recurrent Prostate Cancer after Prostatectomy.

Salvage radiotherapy (SRT) to the prostate bed is the only curative treatment for patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Although several systematic reviews indicated that a dose escalation in the range of 60-70 Gy improved biochemical control, the effects of radiation doses on clinical relapse after SRT remain unclear. Our aim was to investigate the relationship between radiation doses and clinical relapse-free survival (cRFS) after SRT. We identified 295 eligible patients receiving SRT for biochemically recurrent prostate cancer after RP between 2005 and 2018 at 15 institutions. Sixteen patients (5%) received short-term (< 6 months) androgen deprivation therapy (ADT) following RP and/or concurrently with SRT. SRT was delivered to the prostate and seminal vesicle bed using photon beams at a median (range) dose of 66 Gy (61-85) in 1.8-3.0 Gy fractions. The primary outcome was cRFS. Clinical relapse was identified on radiological imaging and/or biopsy and included local recurrence, lymph node metastasis, and distant metastasis. In all analyses, doses were recalculated as an equivalent dose in 2-Gy fractions (EQD2) with α/β = 1.5 Gy. Clinical RFS between the EQD2 ≥ 66 Gy (n = 229) and EQD2 < 66 Gy (n = 66) groups were compared using the Log-rank test, followed by univariate and multivariate Cox regression analyses and a subgroup analysis. The median follow-up duration was 73 months. Among patients with BCR (n = 119), 79 of 96 (82%) in the EQD2 ≥ 66 Gy group and 21 of 23 (91%) in the EQD2 < 66 Gy group received second salvage ADT (p = 0.36). Among all patients (n = 295), clinical relapse was identified in 22 (7%) patients after SRT. Six-year biochemical relapse-free survival (bRFS), cRFS, cancer-specific survival (CSS), and overall survival (OS) rates were 58%, 93%, 98%, and 94%, respectively. Six-year cRFS rates were 94% (95% confidence interval [CI], 90-97) in the EQD2 ≥ 66 Gy group and 87% (95% CI, 75-93) in the EQD2 < 66 Gy group (p = 0.020). The multivariate analysis revealed that EQD2 < 66 Gy, Gleason score ≥ 8, seminal vesicle involvement, and PSA at BCR ≥ 0.5 ng/ml correlated with clinical relapse (p = 0.0016, 0.014, 0.011, and 0.027, respectively). The subgroup analysis showed the consistent benefit of EQD2 ≥ 66 Gy in patients across most subgroups including PSA at BCR after RP, extracapsular extension, and age at SRT. This large multi-institutional observational study demonstrated that a higher SRT dose (EQD2 ≥ 66 Gy) resulted in superior cRFS. The present result supports the dose recommendations in the 2023 National Comprehensive Cancer Network guidelines (64-72 Gy) even in terms of clinical relapse. Prospective trial is warranted to investigate an upper threshold for optimal SRT dose.

Treatment Outcomes of Simultaneous Integrated Boost to Intraprostatic Lesions with External Beam Radiotherapy in Localized Prostate Cancer Patients.

To evaluate the treatment outcomes and toxicity of definitive radiotherapy (RT) for prostate cancer (PC) patients using the simultaneous integrated boost (SIB) technique to intraprostatic lesion (IPL). All the patients received 78 Gy for their prostate ± seminal vesicles and 86 Gy for the IPL using the SIB technique. High-risk patients received pelvic nodal irradiation. The pelvic lymphatic field received 46-54 Gy of radiation. Univariable and multivariable analyses were conducted of the prognostic factors for freedom from biochemical failure (FFBF), progression-free survival (PFS), and PC-specific survival (PCSS) of 619 PC patients who received definitive RT between September 2012 and August 2021. Predictors of late Grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicities were also identified using logistic regression. The median age of the entire cohort was 69 years (range, 47-89 years). Most of the patients (82.7%) had tumors with a GS of 6 or 7, 134 (21.6%) had PC with a GS of 3 + 4, 126 (20.4%) had PC with a GS of 4 + 3, and only 9% had clinical nodal metastasis. The median follow-up time for the entire cohort was 68.5 months (95% CI, 64.4-72.6 months). The 5-year FFBF, PFS, and PCSS rates were 93.2%, 83.2%, and 98.6%, respectively. They were predicted by the serum prostate specific antigen (PSA), Gleason score (GS), clinical nodal stage, and D'Amico risk group. Only 45 patients (7.3%) developed disease recurrence 41.9 months after RT. Of these patients, 12 (1.9% of the total) had BF only, 31 (5.3%) had both BF and distant metastasis, and 2 (0.3%) had distant metastasis only. The 5-year FFBF rates for low-, intermediate-, and high-risk disease were 98.0%, 93.1%, and 88.5%, respectively (p < 0.001). The 5-year PFS and PCSS rates according to risk groups were 91.0%, 82.1%, and 77.4% (p < 0.001), and 99.2%, 96.4%, and 95.9% (p = 0.03), and respectively. GS > 7 and lymph node metastasis negatively predicted FFBF and PCSS in multivariable analysis. Lymph node metastasis was associated with poor PFS, but only marginally (p = 0.06). Ninety (14.6%) and 44 (7.1%) patients had acute Grade ≥ 2 GU and GI toxicities, respectively, and 42 (6.8%) and 27 (4.4%) patients had late Grade ≥ 2 GU and GI toxicities, respectively. Diabetes (OR = 2.61; 95% CI = 1.29-5.26; p = 0.007) and transurethral resection of prostate (OR = 6.75; 95% CI = 3.37-13.54; p = 0.001) independently predicted late Grade ≥ 2 GU toxicity, but no significant predictor of late Grade ≥ 2 GI toxicity was found. Localized PC was effectively and safely treated with definitive RT using the SIB technique to deliver 86 Gy to the IPL in 39 fractions without severe late toxicity. This finding must be validated with long-term results.

Real-world validation of Artificial Intelligence-based Computed Tomography auto-contouring for prostate cancer radiotherapy planning

Background and purposeArtificial Intelligence (AI)-based auto-contouring for treatment planning in radiotherapy needs extensive clinical validation, including the impact of editing after automatic segmentation. The aims of this study were to assess the performance of a commercial system for Clinical Target Volumes (CTVs) (prostate/seminal vesicles) and selected Organs at Risk (OARs) (rectum/bladder/femoral heads + femurs), evaluating also inter-observer variability (manual vs automatic + editing) and the reduction of contouring time. Materials and methodsTwo expert observers contoured CTVs/OARs of 20 patients in our Treatment Planning System (TPS). Computed Tomography (CT) images were sent to the automatic contouring workstation: automatic contours were generated and sent back to TPS, where observers could edit them if necessary. Inter- and intra-observer consistency was estimated using Dice Similarity Coefficients (DSC). Radiation oncologists were also asked to score the quality of automatic contours, ranging from 1 (complete re-contouring) to 5 (no editing). Contouring times (manual vs automatic + edit) were compared. ResultsDSCs (manual vs automatic only) were consistent with inter-observer variability (between 0.65 for seminal vesicles and 0.94 for bladder); editing further improved performances (range: 0.76–0.94). The median clinical score was 4 (little editing) and it was <4 in 3/2 patients for the two observers respectively. Inter-observer variability of automatic + editing contours improved significantly, being lower than manual contouring (e.g.: seminal vesicles: 0.83vs0.73; prostate: 0.86vs0.83; rectum: 0.96vs0.81). Oncologist contouring time reduced from 17 to 24 min of manual contouring time to 3–7 min of editing time for the two observers (p < 0.01). ConclusionAutomatic contouring with a commercial AI-based system followed by editing can replace manual contouring, resulting in significantly reduced time for segmentation and better consistency between operators.

Ten-Year Outcomes of Hypofractionated (45 Gy in 9 Fractions) Intensity Modulated Radiotherapy for Localized Prostate Cancer.

We reported 10-year outcomes of localized prostate cancers treated with hypofractionated intensity-modulated radiotherapy of 45 Gy in 9 consecutive fractions. From October 2011 to April 2017, thirty patients with localized prostate cancer were enrolled in this prospective trial. The median age of the patients was 72.5 years. According to NCCN recurrence risk criteria, eight patients were at low-risk group, 17 at intermediate risk group, 5 at high-risk group. All patients were treated with hypofractionated intensity-modulated radiotherapy (IMRT) of 45 Gy in 9 consecutive fractions to their prostate with or without seminal vesicles. Before radiotherapy, three gold fiducials were implanted into the prostate. In order to reduce the rectal high dose irradiation volume, an inflated rectal balloon was placed in the rectum at simulation and every treatment and patients were treated with comfortable full bladder. Static Intensity-modulated radiotherapy (SIMRT) was applied in 1 patient, Volumetric Modulated Arc Therapy (VMAT) in 27 patients, and tomotherapy in 2 patients. Image guided radiotherapy (IGRT) with gold fiducial registration was adopted. Twenty-six patients also received androgen deprivation therapy (ADT). The median time of ADT was 6 months. Progression⁃free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier analysis. All grade ≥1 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded using Common Terminology Criteria for Adverse Event version 5.0 (CTCAE 5.0) and Radiation Therapy Oncology Group (RTOG) late morbidity criteria, and GU and GI toxicities were cumulatively calculated. After a median follow-up of 102 months (65∼131 months), the 10-year OS was 90.0% (95% confidence interval, 83.3%-96.7%), and the 10-year PFS was 86.5% (95% confidence interval, 79.1%-93.9%). According to CTCAE 5.0, grade 1 acute gastrointestinal (GI) toxicity developed in 12 patients, grade 2 in 2 patients, grade 3 in 2 patients, and grade 1 acute genitourinary (GU) toxicity developed in 12 patients, grade 2 in 2 patients, and no grade 3 or higher toxicity occurred. According to RTOG late morbidity criteria, late (≥3 months after radiotherapy) grade 1 GI toxicity developed in 4 patients (13.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%), and late grade 1 GU toxicity occurred in 1 patient (3.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%). No grade 4 or higher GI and GU toxicities developed. Only one grade 3 GI and one grade 2 GU toxicities were observed for the maximum toxicity at the last follow-up. The potency was not evaluated. The 10-year oncologic outcomes of this shortened hypofractionated IMRT regimen for mainly low/intermediate risk prostate cancer patients is favorable with acceptable acute and late toxicities.

Development and Validation of MRI Imaging Biomarkers for Prostate Cancer Using Deep Learning.

Given the increasing number of treatment options for patients with localized prostate cancer (PCa), there is a need for biomarkers to aid in risk stratification. Specifically, novel biomarkers can aid in the identification of high-risk phenotypes among similar patients in traditional NCCN risk groupings. One promising area for development is using pre-treatment prostate MRI to identify imaging biomarkers to identify prostate cancer patients at highest risk for recurrence. We hypothesized that deep learning could be leveraged to identify imaging biomarkers of aggressive PCa from pre-treatment prostate MRIs. Our study included 1,020 patients treated at our institution between 2010-2022. Given pathologic extraprostatic extension (EPE) and seminal vesicle invasion (SVI) are associated with higher risk of treatment failure, we hypothesized that deep learning models which identified radiographic EPE and SVI would provide non-invasive imaging biomarkers associated with PCa prognosis. We trained two separate deep learning models using convolutional neural networks to predict SVI and EPE respectively. The model inputs were T2W prostate MRIs (n = 894) and models consisted of 8 convolutional layers. Dropout, L2 regularization, and data augmentation were used to improve model generalizability and reduce overfitting. Discriminatory ability of each model was measured using AUC on a blinded external test set of 221 patients. To assess the clinical utility of our imaging biomarkers, log-rank tests were used to evaluate biochemical free survival (BFS) for patients classified as high risk to patients classified as low risk. Biochemical failure was defined as post-treatment PSA >0.1 for patients who underwent radical prostatectomy (RP) or PSA >2ng/ml above nadir for patients receiving radiation therapy. Within our cohort of 1,020 patients the median age was 66 with a median follow up of 4 years. 49.3% (n = 503) underwent RP and 50.7% (n = 517) received EBRT. 4% (n = 41) were low risk, 62.4% (n = 636) were intermediate risk, and 33% (n = 337) were high risk based on NCCN criteria. Deep learning models showed good discriminatory ability for both EPE (AUC 0.66) and SVI (AUC 0.74). Both imaging biomarkers showed prognostic ability to identify high risk prostate phenotypes. Patients deemed high risk based on EPE classifier had worse BFS (median 5 vs 9 years, p<.001). Similarly, patients classified as high risk based on SVI also showed worse BFS (median 5 vs 9 years, p = 0.024). Among intermediate risk patients, EPE biomarker showed an ability to identify high risk phenotypes (median 6 vs 9 years, p = 0.024). Deep learning classifiers of prostate MRIs demonstrated the ability to stratify high-risk prostate cancer phenotypes beyond traditional risk paradigms. Imaging biomarkers represent a non-invasive method to help aid in the personalization of treatment for patients with localized prostate cancer and identify patients who potentially require treatment escalation.

Integration of Multiparameter MRI into Conventional Pretreatment Risk Factors to Predict Adverse Features after Radical Prostatectomy.

The purpose of this study was to Integration of Multiparameter MRI into conventional pretreatment risk factors to develop nomogram for the prediction of adverse features (i.e., positive margin (PM) or extra-prostatic extension (EPE)) indicated for postoperative radiotherapy in patients with prostate cancer. We analyzed 203 histologically proven prostate cancer patients underwent preoperative 3T multiparametric MRI including high b value (0, 1500 s/mm2) diffusion-weighted imaging between 2019 and 2022 at our hospital. Patients with a history of neoadjuvant hormonal therapy, or patients whose surgeon's experience was ≤3 years were excluded. Age, surgical technique, serum PSA level, PSA density, clinical T stage, and biopsy Gleason score were clinical predictors. MRI parameters include prostate volume, tumor size, ECE score, seminal vesicle invasion score, tumor location (apex, peripheral region, or bladder neck), apparent diffusion coefficient (ADC), tumor contact length (TCL), PI-RADS score. Predictors were used in nomograms developed from multivariable logistic regression analysis to estimate the probability of positive margin (PM) or extra-prostatic extension (EPE) after RP. The nomogram's predictive accuracy and discriminative ability were determined by the concordance index with calibration and receiver operating characteristic (ROC) curves. (1) Patient characters: Table 1 lists the MRI characteristics of the patients. Median PSA level is 17.6ng/ml. All patients received extra-fascial resection. 44% of the patients underwent robotic surgery. 24% of the patients had positive margins. In 226 patients who was clinically confined to the prostate, 100 (44%) had a postoperative pathological upgrade of pT3a or above. 46 (29%) of the 158 patients with biopsy grade group (GG)1 was confirmed GG3-5 after RP. Using mpMRI parameters and clinicopathological information, we produced nomograms that may accurately predict adverse Features that are indications for postoperative radiotherapy after RP, which may help individualize treatment decision-making.

Magnetic Resonance Imaging Manifestations in 13 Cases of Seminal Vesicle Tuberculosis.

This study aimed to examine the radiographic manifestations of seminal vesicle tuberculosis (SVT) on magnetic resonance imaging to gain a deeper understanding of this disease. The clinical symptoms, general conditions, relevant laboratory tests and radiological data of 13 patients diagnosed with SVT were collected through bacteriological examination. A descriptive analysis was used to explore the composition ratio and rate values of the collected data. All 13 cases (100.0%) showed isointense signals on T1WI and hypointense signals on T2WI in the affected seminal vesicles, with the disappearance of the multi-chambered high signal on T2WI in normal seminal vesicles. Eight cases (61.5%) showed diffusion restriction on DWI of the affected seminal vesicle and significant enhancement on the contrast scan, whereas five cases (38.5%) showed unrestricted diffusion and mild enhancement on the contrast scan. Patients with significant enhancements exhibited higher counts and neutrophil percentages than patients with mild enhancements, with statistically significant differences (Z = 2.196, P = 0.030; Z = 2.781, P = 0.003, respectively). The counts and percentage of lymphocytes, CD3+T cells and CD4+T cells were significantly lower in patients with significant enhancements than in those with mild enhancements, with statistically significant differences (Z = -2.196, P = 0.030; Z = -2.928, P = 0.002; Z = -2.928, P = 0.002; Z = -2.928, P = 0.002, respectively). Patients with significant enhancements were more likely to have active pulmonary tuberculosis than those with mild enhancements, with a statistically significant difference (P = 0.035). Magnetic resonance imaging reveals distinct radiographic features of SVT, and variations in imaging presentations can indicate a patient's immune status.