UNASSIGNED: Prostate Specific Membrane Antigen (PSMA) - positron emission tomography (PET) guides metastasis-directed radiotherapy (MDRT) in prostate cancer (PrCa). However, its value as a treatment response assessment tool after MDRT remains unclear. Importantly, there is limited understanding of the potential of radiotherapy (RT) to alter PSMA gene (folate hydrolase 1; FOLH1) expression.
UNASSIGNED: We reviewed a series of 11 men with oligo-metastatic PrCa (25 metastasis sites) treated with MDRT before re-staging with 18F-DCFPyL (PSMA) PET upon secondary recurrence. Acute effects of RT on PSMA protein and mRNA levels were examined with qPCR and immunoblotting in human wild-type androgen-sensitive (LNCap), castrate-resistant (22RV1) and castrate-resistant neuroendocrine (PC3 and DU145) PrCa cell lines. Xenograft tumors were analyzed with immunohistochemistry. Further, we examined PSMA expression in untreated and irradiated radio-resistant (RR) 22RV1 (22RV1-RR) and DU145 (DU145-RR) cells and xenografts selected for survival after high-dose RT.
UNASSIGNED: The majority of MDRT-treated lesions showed lack of PSMA-PET/CT avidity, suggesting treatment response even after low biological effective dose (BED) MDRT. We observed similar high degree of heterogeneity of PSMA expression in both human specimens and in xenograft tumors. PSMA was highly expressed in LNCap and 22RV1 cells and tumors but not in the neuroendocrine PC3 and DU145 models. Single fraction RT caused detectable reduction in PSMA protein but not in mRNA levels in LNCap cells and did not significantly alter PSMA protein or mRNA levels in tissue culture or xenografts of the other cell lines. However, radio-resistant 22RV1-RR cells and tumors demonstrated marked decrease of PSMA transcript and protein expression over their parental counterparts.
UNASSIGNED: PSMA-PET may be a promising tool to assess RT response in oligo-metastatic PrCa. However, future systematic investigation of this concept should recognize the high degree of heterogeneity of PSMA expression within prostate tumors and the risk for loss of PSMA expression in tumor surviving curative courses of RT.

UNASSIGNED: To report the results of the Single Fraction Early Prostate Irradiation (SiFEPI) phase 2 prospective trial.
UNASSIGNED: The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and favorable-intermediate (FIR) risk prostate cancers. After rectal spacer placement, a single fraction of 20 Gy was delivered to the prostate. Oncological outcome (biochemical (bRFS) and local (lRFS) relapses, disease-free (DFS) and overall (OS) survivals and toxicity (acute/late genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities were investigated.
UNASSIGNED: From 03/2014 to 10/2017, 35 pts were enrolled, of whom 33 were evaluable. With a median age of 66 y [46-79], 25 (76 %) and 8 (24 %) pts were LR and FIR respectively. With a MFU of 72.8 months [64-86], 6y-bRFS, lRFS and mRFS were 62 % [45-85], 61 % [44-85] and 93 % [85-100] respectively while 6y-DFS, CSS and OS were 54 % [37-77], 100 % and 89 % [77-100] respectively. Late GU, GI and S toxicities were observed in 11 pts (33 %;18G1), 4 pts (12 %;4G1) and 7 pts (21 %;1G1,5G2,1G3) respectively. Biochemical relapse (BR) was observed in 11 pts (33 %;7LR,4FIR) with a median time interval between HDB and BR of 51 months [24-69]. Nine of these pts (82 %) presented a histologically proven isolated local recurrence.
UNASSIGNED: Long-term results of the SiFEPI trial show that a single fraction of 20 Gy leads to sub-optimal biochemical control for LR/FIR prostate cancers. The late GU and GI toxicity profile is encouraging, leading to consideration of HDB as a safe irradiation technique.

UNASSIGNED: To analyze the oncological outcome in elderly (>70 years) prostate cancer after high-dose rate brachytherapy (HDB) boost.
UNASSIGNED: In this retrospective study, patients with intermediate (IR) and high-risk (HR) prostate cancer underwent external beam radiation therapy (EBRT) followed by HDB boost with/without androgen deprivation therapy (ADT). The impact of age (≤70y vs. > 70y) was investigated. Oncological outcome focused on biochemical relapse-free survival (bRFS), cause-specific (CSS) and overall survival (OS). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were investigated.
UNASSIGNED: From 07/08 to 01/22, 518 pts received a HDB boost, and 380 were analyzed (≤70y:177pts [46.6%] vs. > 70y:203pts [53.4%]). Regarding NCCN classification, 98 pts (≤70y: 53pts; >70y: 45pts; p = 0.107) and 282 pts (≤70y: 124pts; >70y: 158pts; p = NS) were IR and HR pts respectively. Median EBRT dose was 46 Gy [37.5-46] in 23 fractions [14-25]. HDB boost delivered a single fraction of 14/15 Gy (79%). ADT was used in 302 pts (≤70y: 130pts; >70y: 172pts; p = 0.01). With MFU of 72.6 months [67-83] for the whole cohort, 5-y bRFS, 5-y CSS and 5-y OS were 88% [85-92], 99% [97-100] and 94% [92-97] respectively; there was no statistical difference between the two age groups except for 5-y CSS (p = 0.05). Late GU and GI toxicity rates were 32.4% (G ≥ 3 7.3%) and 10.1% (no G3) respectively.
UNASSIGNED: For IR and HR prostate cancers, HDB boost leads to high rates of disease control with few late G ≥ 3 GU/GI toxicities. For elderly pts, HDB boost remains warranted mainly in HR pts, while competing comorbidity factors influence OS.

UNASSIGNED: Approximately 7% of patients with newly diagnosed prostate cancer (PCa) in the US will have have metastatic disease. The dogma that there is no role for surgery in this population has been questioned recently. Here we report long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy.
UNASSIGNED: This is a multicenter phase 1 trial. The major inclusion criterion was biopsy proven N1M0 or NxM1a/b PCa. Primary end point was the Clavien-Dindo-based major complication rate. Secondary outcomes were biochemical progression and overall survival. RNA-seq correlative study was conducted in nine select cases as a pilot study.
UNASSIGNED: Final accrual was 32 patients of which 25 and 7 were cNxM1 and cN1M0, respectively. With the median follow-up of 46 months (interquartile range 31.7 - 52.7 months), 25 out of the 32 patients (75%) were alive at the time of last contact. There were three disparate groups based on the oncologic outcome: favorable, intermediate, and poor. In seven men with favorable response, androgen deprivation therapy was switched to intermittent approach and five remain free of any evidence of disease after more than two years off all systemic therapy with the normalization of serum testosterone. Of these five patients, three had M1 disease. Long-term use of one pad or less per day was 80%. RNA-seq analysis revealed an enriched downregulation of tumor necrosis factor (TNF)-α signature in the favorable group.
UNASSIGNED: Overall long-term oncologic outcome of cytoreductive radical prostatectomy was significantly higher than historical results. Importantly, the combination of surgery with systemic therapy may result in a long durable response in a minority of men who present with metastatic PCa.

Prostatic PIRADS 4 and 5 lesions on multiparametric MRI typically represent adenocarcinoma with small lymphocytic lymphoma being a rare pathological finding. We report a case of small lymphocytic lymphoma masquerading as PIRADS 4 and 5 lesions with associated lymphadenopathy in a 69-year-old male on active surveillance for low-risk prostate cancer that was subsequently confirmed on targeted and systematic prostate biopsy. Following treatment of lymphoma with ibrutinib, there was complete resolution of the PIRADS lesions on follow-up mpMRI.

Approximately 25% of patients who have undergone extensive systemic therapy for advanced metastatic castration-resistant prostate cancer (mCRPC) develop treatment associated neuroendocrine prostate cancer (NEPC). 177Lu-prostate specific membrane antigen (-PSMA) is an emerging alternative therapy for mCRPC patients who have exhausted other systemic therapy options; however, cells with neuroendocrine differentiation do not express PSMA and are not affected by this treatment. This case highlights an exceptional response of skeletal metastases to 177LuPSMA that is undermined by neuroendocrine transformation in the liver.

Prostate cancer is the fifth most common malignancy worldwide and the second most common in men. It usually metastasizes to bony skeleton, followed by lung, liver, pleura and adrenals. We report a 71 year old male patient who initially presented only with retroperitoneal lymphadenopathy and constitutional symptoms, misleading the diagnosis of retroperitoneal lymphoma. Who later on was discovered to have carcinoma prostate.

Non-Hodgkin lymphoma of the prostate is uncommon. Prostate specific antigen and transrectal ultrasound do not aid in diagnosis. Survival and treatment options are ultimately based on immune-histologic subtype and stage. Lower urinary tract symptoms attributed to lymphoma of the prostate can be refractory to systemic treatments as well as transurethral resection. This case provides the first description of the longitudinal clinical course of treatment-refractory localized Non-Hodgkin lymphoma of the prostate.

Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials. Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies. The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.

OBJECTIVE: For patients with local recurrent disease after radical prostatectomy (35-54%) salvage radiotherapy (SRT) is the treatment of choice. In the post prostatectomy setting, SRT may impose risk at increased toxicity. As data on long-term toxicity, especially on urinary incontinence, are scarce, we report on the long-term treatment outcomes, toxicity and urinary incontinence rates after SRT.
METHODS: Patients with biochemically recurrent prostate cancer after radical prostatectomy, who were treated with SRT (3D-CRT) at our institution between 1998 and 2012, were included in this retrospective cohort analysis. Primary endpoint was urinary incontinence rate. Secondary endpoints were acute and late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicity rates, biochemical progression-free survival (bPFS), distant metastasis-free survival (DMFS), disease specific survival (DSS), and overall survival (OS).
RESULTS: 244 patients were included. Median follow-up after SRT was 50 months (range: 4-187 months). Before start of SRT 69.7% of patients were continent for urine. After SRT de novo urinary incontinence complaints (grade ≥ 1) occurred in the respective acute and late phase in 6.1% and 17.6% of patients. Respective acute grade ≥2 GU and GI toxicity was 19.2% and 17.6%. Late grade ≥2 toxicity for GU was 29.9% and for GI was 21.3%, respectively. The respective 5-year bPFS, OS, DSS and DMFS rates were 47.6%, 91.8%, 98.8% and 80.5%.
CONCLUSIONS: Experience at our institution with SRT demonstrates that this results in good long-term biochemical control. However, toxicity and urinary incontinence rates were high.