Michael J Zelefsky

• Memorial Sloan Kettering Cancer Center

Purpose To explore pragmatic approaches integrating MRI and PSMA-PET/CT for evaluating extraprostatic extension (EPE) of prostate cancer (PCa). Methods Consecutive patients with newly-diagnosed PCa that underwent multiparametric MRI and PSMA-PET/CT, followed by radical prostatectomy in 2021–2024 were included. Imaging parameters assessed on both m...

Prostate-specific membrane antigen (PSMA)-PET/CT has become integral to management of prostate cancer; however, PSMA-avid rib lesions pose a diagnostic challenge. This study investigated clinicopathological and imaging findings that predict metastatic etiology of PSMA-avid rib lesions. Consecutive patients with prostate cancer that underwent PET/CT...

Prostate cancer is the most common cancer and the second leading cause of cancer death among men in the United States. Definitive treatment with either surgery or radiation (with or without androgen deprivation therapy, ADT) is currently guided by the National Comprehensive Cancer Network’s (NCCN) risk stratification prognostic groupings, which are...

Objectives To evaluate the incidence and degree of rectal wall infiltration (RWI) of spacer gel used during prostate radiotherapy among two practitioners experienced in using rectal spacers. Materials and methods Consecutive patients with prostate cancer who received prostate radiotherapy after hydrogel rectal spacer insertion in August 2023–Augus...

Purpose Screening colonoscopies (CS) performed before prostate stereotactic body radiation therapy (SBRT) allow for identifying synchronous malignancies and comorbid gastrointestinal (GI) conditions. Performing these procedures prior to radiation precludes the necessity of post-SBRT pelvic instrumentation, which may lead to severe toxicity and fist...

An increasing number of patients with prostate cancer (PCa) undergo assessment with magnetic resonance imaging (MRI) and prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT). This offers comprehensive multimodality staging but can lead to discrepancies. The objective was to assess the rates and types of...

Background: Pelvic reirradiation of de novo rectal or anal cancer after prior prostate cancer RT poses a significant risk of urinary and rectal fistula. In this report we describe the use of a rectal spacer to improve dosimetry and reduce this risk. Methods: Patients undergoing anorectal radiotherapy (RT) after prior prostate RT who had a rectal sp...

Purpose Rectal spacers have gained popularity as a dose-sparing material for prostate cancer radiation therapy (RT). However, the procedure can be associated with unintended rectal wall infiltration (RWI) of the spacer gel. We therefore classified RWI severity as a function of depth and explored its association with rectal toxicity using a data set...

Prostate-specific membrane antigen (PSMA) PET/CT has an established reliable diagnostic performance for detecting metastases in prostate cancer. However, there are increasing instances of scans demonstrating equivocal bone lesions, with non-specific uptake and without a definite benign or malignant CT correlate. To date, the prevalence, malignancy...

A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Methods: Six patients with 9 prostate-specific membrane antigen (PS...

Purpose: Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated...

BACKGROUND Various radiotherapeutic regimens are used in the treatment of bladder cancer. OBJECTIVE We aimed to evaluate early toxicity and outcomes associated with hypofractionated radiation therapy (Hypo-RT), 55Gy in 20 fractions. MATERIAL AND METHODS We identified 40 patients who received definitive Hypo-RT for localized bladder cancer. Most p...

Purpose Brain metastases are rare in patients with prostate cancer and portend poor outcome. Prostate-specific membrane antigen positron emission tomography (PSMA PET)/CT scans including the brain have identified incidental tumors. We sought to identify the incidental brain tumor detection rate of PSMA PET/CT performed at initial diagnosis or in th...

Background and purpose: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations...

Background Dose escalation radiotherapy enables increased control of prostate cancer (PCa) but requires segmentation of dominant index lesions (DIL). This motivates the development of automated methods for fast, accurate, and consistent segmentation of PCa DIL. Purpose To construct and validate a model for deep‐learning‐based automatic segmentatio...

Dose escalation radiotherapy allows increased control of prostate cancer (PCa) but requires segmentation of dominant index lesions (DIL), motivating the development of automated methods for fast, accurate, and consistent segmentation of PCa DIL. We evaluated five deep-learning networks on apparent diffusion coefficient (ADC) MRI from 500 lesions in...

Purpose: The International Prostate Symptom Score (IPSS) is a widely used tool for evaluating patient-reported lower urinary tract symptoms. In this study, we assessed patients with prostate cancer and their understanding of IPSS questions. Methods and materials: Consecutive patients with prostate cancer (N = 144) self-completed an online IPSS q...

Introduction: Using an magnetic resonance linear accelerator (MR-Linac) may improve the precision of visible tumor boosting with ultra-hypofractionation by accounting for daily positional changes in the target and organs at risk (OAR). Patients and methods: Fifteen patients with prostate cancer and an MR-detected dominant lesion were treated on...

Background: Keratinocyte carcinomas are amenable to many treatments, including radiotherapy (RT). Electronic skin surface brachytherapy (ESSB) enables the precise delivery of radiation without radioisotopes. Objectives: In this prospective multicenter clinical trial, we characterized early outcomes of ESSB prospectively through both patient- and...

Purpose/Objective(s) Erectile dysfunction is a common side effect of prostate cancer treatment, including prostate radiotherapy (RT). Vessel-sparing RT with avoidance of the internal pudendal artery (IPA) has shown promising rates of erectile function in non-randomized data. Implementation of vessel-sparing RT can be complicated by factors such as...

Purpose/Objective(s) Local recurrences after previous radiotherapy (RT) are increasingly being identified with increasing use of molecular imaging in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option for radiorecurrent prostate cancer. While supported by multiple prospec...

Purpose/Objective(s) Focal boosting of the dominant intraprostatic lesion (DIL) improves biochemical control. The MR-linear accelerator (MRL) may improve the precision of DIL boosting with ultrahypofractionation by accounting for daily changes in the target and organs at risk (OAR). We report our early experience using this approach. Materials/Met...

Purpose/Objective(s) SCC and BCC are amenable to a variety of treatments. ESSB has emerged as a novel option which enables precise delivery of radiotherapy (RT), potentially limiting side effects. In a prospective multicenter clinical trial, we characterized early outcomes of ESSB, hypothesizing that it affords cosmesis superior to what has been pr...

Purpose/Objective(s) To compare post-treatment biopsy outcomes for clinically localized prostate cancer patients treated with high-dose conventionally fractionated intensity modulated radiotherapy (CF- IMRT) versus high-dose stereotactic body radiotherapy (SBRT). Materials/Methods 451 patients with low and intermediate risk prostate cancer treated...

Purpose/Objective(s) Combined brachytherapy and external beam radiotherapy is an accepted treatment for unfavorable intermediate-risk and high-risk prostate cancer. We compared genitourinary and gastrointestinal toxicity of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy boost when combined with ultra-hypofractionated external beam radia...

Purpose/Objective(s) MR-guided systems, such as hybrid MR-Linacs, provide a novel platform for the acquisition and development of image-based biomarkers that can provide crucial information during daily online plan adaptation. Relaxometry has been shown to be sensitive to changes in tissue composition or function during radiotherapy. We investigate...

Purpose To develop ABCD, an HDR brachytherapy prostate optimizer with mixed bound and unbound functionalities and evaluate its performance. Materials and Methods ABCD utilized linear optimization with iterative constraint refinement. ABCD aims to maximize (unbounded) dose to voxels within the prostate while achieving bounded constraints on organs-...

In almost all cases, initial management of testicular cancer involves a radical inguinal orchiectomy. Post-operative management depends on histological subtype and extent of disease. The most common type of testicular germ cell tumor is seminoma, which is a highly radiosensitive neoplasm. Post-operative radiation is a standard option for stage I-II...

Intensity-modulated radiation therapy (IMRT) is the standard technique for external beam radiation therapy (EBRT) for prostate adenocarcinoma. IMRT is used in both the definitive setting (alone or combined with brachytherapy) and post-operatively (adjuvant or salvage). Various fractionation schemes exist; however, all approaches rely on accurate ta...

Introduction Radiation therapy (RT) for anorectal cancer after prior prostate cancer RT is usually avoided due to concern for complications. Data on this topic is scarce. Our aim was to evaluate tolerability, toxicity, and clinical outcomes associated with a second course of pelvic radiation in men with de novo anorectal cancers previously treated...

Objective To characterize patterns of failure using prostate-specific membrane antigen positron emission tomography (PSMA PET) after radical prostatectomy (RP) and salvage radiotherapy (SRT). Methods Patients with rising PSA post-RP+SRT underwent ⁶⁸Ga‐HBED‐iPSMA PET/CT on a single-arm, prospective imaging trial (NCTXXXXXXXX). Scans were centrally...

Purpose/Objective To compare toxicity profiles of low-dose rate (LDR) and high-dose rate (HDR) brachytherapy boost combined with ultra-hypofractionated external beam radiation therapy (UH-EBRT). Materials/Methods 99 patients with intermediate-risk prostate cancer underwent an HDR (n = 59) or LDR (n = 40) boost combined with UH-EBRT (5 Gy x 5) . HD...

PURPOSE Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted commun...

Background A positive post-treatment prostate biopsy following definitive radiotherapy carries significant prognostic implications. Objective To determine whether local recurrences after prostate stereotactic body radiation therapy (SBRT) are associated with the presence of and occur more commonly within the region of a PI-RADS 4 or 5 dominant int...

245 Background: SBRT for localized prostate cancer (PCa) is the focus of several ongoing and reported high-impact trials, which often focus on physician-reported toxicity (P-Tox) when comparing regimens. Patient-reported quality of life (PR-QoL) may differ and provide a more sensitive comparative metric of treatment burden, especially with fewer pr...

507 Background: Chemoradiation (CRT) for bladder cancer provides comparable outcomes to radical cystectomy; however, concerns regarding toxicity, particularly in elderly, frail patients limit its utilization. Methods: We identified 150 consecutive patients who underwent definitive CRT for T1-4N0M0 bladder cancer at Memorial Sloan Kettering Cancer C...

Purpose/Objective(s) The International Prostate Symptom Score (I-PSS) is a widely used tool for the evaluation of patient-reported lower urinary tract symptoms (LUTS). Urologists and Radiation Oncologists frequently use the I-PSS to help determine a prostate cancer patient's eligibility for a type of treatment, and to follow up quality-of-life outc...

Purpose/Objective(s) Although clinical trial enrollment is critical to development of new cancer therapies, < 5% of cancer patients in the United States enroll onto trials. Participation is particularly low among underrepresented minority groups, who comprise < 20% of enrollments. Community-academic partnerships have the potential to improve patien...

Purpose/Objective(s) Hydrogel rectal spacer placement (HSP) has been shown to minimize rectal dose during prostate cancer radiotherapy, yet its potential benefit for modulating rectal toxicity could in large part depend upon the quality of prostate-rectal separation achieved from HSP. We therefore developed a practical quality metric to evaluate HS...

Purpose/Objective(s) The purpose of this study was to evaluate if a minimum bladder reference contour could help reduce treatment delays and imaging needed for pre-treatment setup in patients undergoing prostate stereotactic body radiation therapy (SBRT). Materials/Methods 20 patients undergoing 5-fraction SBRT to the prostate and seminal vesicles...

Purpose/Objective(s) Financial toxicity is increasingly recognized but poorly characterized in the context of prostate cancer. The purpose of this study was to evaluate the magnitude of financial toxicity experienced by men with localized prostate cancer treated with definitive radiation therapy (RT) at a comprehensive cancer center. Materials/Met...

Objective To determine the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low‐dose‐rate (LDR) brachytherapy, with or without supplemental external beam radiotherapy (EBRT). Patients and Methods A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy...

PURPOSE The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachyth...

Introduction: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat metastatic oligorecurrence and locoregional recurrences but limited evidence/guidance exists in the setting of pelvic re-irradiation. An international Delphi study was performed to develop statements to guide practice regarding patient selection, pre-treatment in...

PURPOSE This study evaluated outcomes associated with a high-dose-rate (HDR) brachytherapy boost combined with stereotactic body radiation therapy (SBRT) for patients with higher-risk localized prostate cancer. MATERIALS AND METHODS We identified 101 patients with National Comprehensive Cancer Network high-risk, unfavorable intermediate-risk, or f...

Background: Sildenafil citrate has been shown to be protective of sexual function when given concurrently and following prostate radiation therapy (RT), but some evidence suggests an increased biochemical recurrence (BCR) risk in patients taking sildenafil after radical prostatectomy. Aim: To evaluate whether sildenafil use is associated with in...

Purpose: To quantitatively evaluate through automated simulations the clinical significance of potential high-dose rate (HDR) prostate brachytherapy (HDRPB) physics errors selected from our internal failure-modes and effect analysis (FMEA). Methods and materials: A list of failure modes was compiled and scored independently by 8 brachytherapy ph...

e17053 Background: Cancer patients’ potential for severe financial toxicity (FT) is well-established, however there is limited data on the magnitude of this challenge associated with treatment of localized prostate cancer (PC). The extent to which men consider potential financial implications prior to selection of a treatment strategy remains poorl...

5012 Background: Standard of care in VHR PCa is radiation therapy (RT) with 18-36 months (mos) of androgen-deprivation therapy (ADT). With this regimen, chronic ADT toxicity is significant and biochemical recurrence (BCR) frequent. We sought to improve tumor control and minimize toxicity with intensified short course ADT with dual androgen receptor...

Background and Purpose Artificial intelligence advances have stimulated a new generation of autosegmentation, however clinical evaluations of these algorithms are lacking. This study assesses the clinical utility of deep learning-based autosegmentation for MR-based prostate radiotherapy planning. Materials and Methods Data was collected prospectiv...

Purpose High-Dose Stereotactic Ablative Radiotherapy (SAbR) for prostate cancer (PCa) offers the radiobiologic potency of the most intensified radiation therapy regimens, but was associated with >90% rates of ulceration of the anterior rectal wall on endoscopic assessment that infrequently progressed to severe rectal toxicity in prior prospective s...

Purpose To investigate predictors associated with post-treatment biopsy outcomes after stereotactic body radiotherapy (SBRT) for localized prostate cancer. Materials and methods 257 patients treated with prostate SBRT to dose levels of 32.5 Gy to ≥40 Gy in 5–6 fractions underwent a post-treatment biopsy performed approximately two years after trea...

Background Salvage partial gland ablation (sPGA) has been proposed to treat some localized radiorecurrent prostate cancer. The role of prostate biopsy and magnetic resonance imaging (MRI) characteristics to identify patients eligible for sPGA is unknown. Objective To evaluate the ability of MRI and prostate biopsy characteristics to identify an in...

Purpose This prospective phase III randomized trial was designed to test whether ultra-high single-dose radiotherapy (24 Gy SDRT) improves local control of oligometastatic lesions over a standard hypofractionated stereotactic body radiotherapy regimen (3 x 9 Gy SBRT). The secondary endpoint was to assess the associated toxicity and the impact of ab...

Purpose: To investigate whether T2-weighted magnetic resonance imaging (MRI) findings could improve upon established prognostic indicators of metastatic disease and cancer-specific survival. Materials and methods: For a cohort of 3,406 consecutive men who underwent prostate MRI before definitive prostatectomy (n=2,160) or radiotherapy (n=1,246)...

Importance In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus. Objective To develop and validate a pretreatment clinical prognostic sta...

Abstract Background To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. Methods Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instruc...

Background There are limited data regarding high-dose stereotactic body radiation therapy (SBRT) for prostate cancer in patients with poor baseline urinary function. The purpose of this study was to evaluate genitourinary (GU) toxicity and changes in patient reported symptom severity scores after prostate SBRT in men with high pre-treatment Interna...

Background and purpose Magnetic Resonance (MR)-only planning has been implemented clinically for radiotherapy of prostate cancer. However, fewer studies exist regarding the overall success rate of MR-only workflows. We report on successes and challenges of implementing MR-only workflows for prostate. Materials and methods A total of 585 patients w...

Background: Radiation therapy is one of the most commonly used cancer therapeutics, but genetic determinants of clinical benefit are poorly characterized. Pathogenic germline variants in ATM are known to cause ataxia-telangiectasia, a rare hereditary syndrome notable for marked radiosensitivity. In contrast, somatic inactivation of ATM is a common...

Purpose: To report early toxicity and tumor control outcomes of Pd-103 brachytherapy with ultrahypofractionated stereotactic radiation therapy (RT) for intermediate-risk prostate cancer. Methods and materials: This prospective trial included 40 patients with intermediate-risk prostate cancer who underwent low-dose-rate (Pd-103) brachytherapy (pr...

Purpose STAMPEDE reported overall survival (OS) benefits for prostate-directed radiotherapy (PDRT) in low-burden metastatic prostate cancer. Oligometastasis-directed radiotherapy (ORT) improves androgen deprivation therapy (ADT)-free and progression-free survivals. Comprehensive PDRT+ORT to all detectable metastases may offer benefit for de novo ol...

Background This study reports clinical experience using a linear accelerator-based MV-kV imaging system for intra-fraction motion management during prostate SBRT. Methods From June 2016 to August 2018, 193 prostate SBRT patients were treated using MV-kV motion management (median dose 40 Gy in 5 fractions). Patients had three fiducials implanted th...

Background To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. Methods Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to m...

Background: To evaluate inter-fractional variations in bladder and rectum during prostate stereotactic body radiation therapy (SBRT) and determine dosimetric and clinical consequences. Methods: Eighty-five patients with 510 computed tomography (CT) images were analyzed. Median prescription dose was 40 Gy in 5 fractions. Patients were instructed to...

Purpose: To evaluate 11C-choline PET/CT detection performance for biochemically recurrent prostate cancer (PCa) in a large non-European cohort in the context of emerging evidence for PSMA PET in this setting, and to map patterns of PCa recurrence. Methods: We retrospectively analyzed 11C-choline PET/CT scans from 287 patients who were enrolled onto...

OBJECTIVE. Despite a substantial increase in the use of MRI for pretreatment evaluation of prostate cancer, its prognostic value in patients undergoing radiation therapy (RT) is not well known. Therefore, the purpose of this study was to systematically review the literature and perform a meta-analysis on the prognostic value of pretreatment MRI in...

Background and purpose: To identify early biochemical predictors of survival in intermediate- and high-risk prostate cancer patients with a pre-treatment PSA <20 ng/mL following definitive radiation therapy (RT) and androgen deprivation therapy (ADT). Materials and methods: A single-institution review of 2566 intermediate and high-risk prostate...

Background: Studies using stereotactic body radiotherapy (SBRT) dose escalation in in low- and intermediate-risk prostate cancer patients have indicated favorable outcomes. Objective: To evaluate tolerance and tumor control outcomes in low- and intermediate-risk prostate cancer patients treated with high-dose SBRT following our phase 1 trial. D...

Background and purpose: Magnetic resonance (MR) only radiation therapy for prostate treatment provides superior contrast for defining targets and organs-at-risk (OARs). This study aims to develop a deep learning model to leverage this advantage to automate the contouring process. Materials and methods: Six structures (bladder, rectum, urethra, p...

Purpose: To determine the impact of using fiducial match for daily image-guidance on pelvic lymph node (PLN) coverage for prostate cancer patients receiving stereotactic body radiation therapy (SBRT). Methods: Thirty patients underwent SBRT treatment to the prostate and PLN from 2014 to 2016. Each patient received either 800cGy × 5 or 500cGy × 5...

Context: Recent studies suggested that magnetic resonance imaging (MRI) followed by targeted biopsy (“MRI-stratified pathway”) detects more clinically significant prostate cancers (csPCa) than the systematic transrectal ultrasound-guided prostate biopsy (TRUS-Bx) pathway, but controversy persists. Several randomized clinical trials (RCTs) were rece...

Purpose: The use of magnetic resonance imaging (MRI) for radiation therapy simulation is growing because of its ability to provide excellent delineation of target tissue and organs at risk. With the use of hypofractionated schemes in prostate cancer, urethral sparing is essential; however, visualization of the prostatic urethra can be challenging...

Purpose: To develop an Eclipse plug-in (MLC_MODIFIER) that automatically modifies control points to expose fiducials obscured by MLC during VMAT, thereby facilitating tracking using periodic MV/kV imaging. Method: Three-dimensional fiducial tracking was performed during VMAT by pairing short-arc (3°) MV digital tomosynthesis (DTS) images to trig...

e16563 Background: Few data exist on CTC frequency and number, genetic landscape, and tumor mutational burden (TMB) in VHR, node negative, localized prostate cancer (PCa). Methods: We are conducting a single-arm phase 2 trial of ultra-hypofractionated radiation (RT) with 6 months of abiraterone, apalutamide and leuprolide in VHR PCa, defined as: Gl...

Purpose: To report toxicity outcomes, prostate-specific antigen (PSA) relapse, and cumulative incidence posttreatment biopsy results among patients treated on a prospective dose escalation study using ultra-hypofractionated stereotactic body radiation therapy (SBRT) for patients with low- and intermediate-risk prostate cancer. Methods and materia...

Purpose: To report 15-year outcomes for dose-escalated intensity modulated radiation therapy (IMRT) for localized prostate cancer (PC) by evaluating biochemical relapse, distant metastases, cancer-specific survival, and long-term toxicity. Methods and materials: A database search was conducted for the first cohort of patients treated at this ins...

Purpose: We determined the prognostic importance of a positive posttreatment biopsy after prostate radiotherapy. Materials and methods: A total of 382 patients underwent a posttreatment biopsy after external beam radiotherapy of clinically localized prostate cancer. Posttreatment biopsies were classified as positive (prostatic adenocarcinoma wit...

Purpose: The current oligometastatic (OM) model postulates that the disease evolves dynamically with sequential emergence of OM (SOM) lesions requiring successive rounds of SOM ablation to afford tumor cure. The present phase 2 study explores the ablative efficacy of 24 Gy single-dose radiation therapy (SDRT), its feasibility in diverse OM setting...