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Purpose: We investigated the impact of prostate-specific membrane antigen (PSMA) PET/CT compared with conventional imaging on treatment outcomes for node-positive prostate cancer (PCa) patients who underwent androgen deprivation therapy (ADT) and external radiotherapy (RT)., Patients and Methods: A multicentric, retrospective study recruited patients with node-positive PCa patients who underwent conventional radiological evaluation or PSMA PET/CT and received ADT and RT at 3 hospitals from 2009 to 2021 were enrolled. Patients underwent prostate and pelvis RT, accompanied by a minimum of 6 months of ADT. The primary endpoints were progression-free survival (PFS) and PCa-specific survival (PCSS). Cox regression analyzed the association of survival with potential prognostic factors, whereas logistic regression identified the predictors of bone and lymph node metastasis., Results: The median follow-up time was 64.0 months. The majority of patients (64.1%) underwent PSMA PET/CT for staging. The 5-year rates of PFS and PCSS were 63.7% and 83.7%, respectively. Disease progression was observed in 90 patients (36.3%). In multivariable analysis, ADT duration of less than 24 months and post-RT prostate-specific antigen (PSA) nadir were prognostic for PFS. Early clinical T stage and PSMA PET/CT predicted better PCSS. Patients staged with PSMA PET/CT had exhibited significantly higher 5-year PCSS rates than compared with those staged with conventional imaging (95.1% vs 76.9%; P = 0.01). Shorter ADT duration and higher PSA levels after RT independently predicted bone metastasis in multivariable logistic regression. Advanced T stage, shorter ADT duration, and higher PSA levels after neoadjuvant ADT predicted nonregional lymph node recurrence., Conclusions: ADT with pelvis RT is an effective treatment option for node-positive PCa patients. The PSMA PET/CT outperformed conventional imaging in PCSS, emphasizing the importance of precise clinical staging for patients undergoing definitive RT., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To compare the biochemical failure (FFBF) and prostate cancer specific survival (PCSS) rates of patients with intermediate-risk prostate cancer (IR-PC) who were treated with 6 months of androgen deprivation therapy (ADT) with 78 Gy to the prostate, those treated with ADT and focal boost (FB) of 86 Gy to intraprostatic lesion (IPL) using the simultaneous-integrated boost (SIB) technique, and those treated with SIB alone., Materials and Methods: A retrospective analysis of 320 IR-PC patients treated between January 2012 and April 2021 was performed. Patients were divided into three groups based on their treatment arm: 78 + ADT (109 patients, 34.1%), 78/86 (102 patients, 31.8%), and 78/86 + ADT. Univariable and multivariable analyses were used to determine prognostic factors for FFBF and PCSS., Results: Median follow-up was 8.8 years. The 8-year FFBF and PCSS rates were 88.6% and 99.0%. Patients who received ADT had significantly higher pretreatment PSA levels and clinical tumor stage. Disease progression occurred in 45 patients (7.3%) at a median of 41.9 months after definitive radiotherapy (RT). Younger age, positive core biopsy (PCB) ≥ 50%, and the absence of ADT were all independent predictors of poor FFBF in multivariate analysis, whereas patients with PCB < 50% who were also given ADT had better PCSS. Patients treated with 78/86 Gy alone had worse FFBF than those treated with 78 Gy and ADT (Hazard ratio [HR] = 3.39 [95% CI = 1.46-7.88]; p = 0.005), as well as than those treated with 78/86 Gy and ADT (HR = 3.21 [95% CI = 1.23-6.46]; p = 0.009). However, FB to IPL has no effect on PCSS in multivariable analysis. There was no significant difference between treatment groups in terms of acute and late Grade ≥2 genitourinary or gastrointestinal toxicity., Conclusions: Our findings demonstrated that patients who received 78/86 alone did worse than patients who received ADT with either 78 or 78/86 Gy. However, because IR-PC patients are so diverse, additional prospective trials are needed to validate our findings., (© 2024 Wiley Periodicals LLC.)

Background: We examined the effects of reducing the planning target volume (PTV) margin in MR-guided radiotherapy (MRgRT) on the distribution of radiation dose to target volumes and organs-at-risk (OARs). Thus, we compared MR-Linac (MRL) plans with and without reduced margin and intensity-modulated radiotherapy (IMRT) plan with conventional linac for low-risk prostate cancer patients receiving 36.25 Gy in five fractions of ultra-hypofractionated radiation therapy., Materials and Methods: Twenty low-risk prostate cancer patients treated with 1.5 T MR-Linac were evaluated. The same planning CT images were used for four plans: the MRL-R plan with reduced margin planning target volume (PTV-R) and the MRL-N plan with normal margin PTV (PTV-N), which is also used for IMRT plan. In four plans, PTV doses, organs-at-risk (OARs) doses, the homogeneity index (HI), and monitor units were compared., Results: All plans met the criteria for PTV coverage and OARs dose constraints. The maximum and mean PTV doses were significantly higher in the MRL-R and MRL-N plans compared to the IMRT plan. The HI was lowest in the IMRT plan (0.040 ± 0.013) and highest in the MRL-N plan (0.055 ± 0.012; p < 0.001). There was no significant difference in the PTV dosimetric parameters between the MRL-R and the MRL-N plans. The high doses in the rectum was significantly lower in the MRL-R compared to other plans. The bladder V36.25 Gy was significantly lower in the MRL-R plan (2.43 ± 1.87 Gy) compared to MRL-N (4.50 ± 2.42 Gy; p < 0.001), and IMRT plans (4.76 ± 2.77 Gy; p < 0.001). There was no significant difference in the low-dose volumes of the body, maximum femur doses, or monitor units across each plan., Conclusions: Ultra-hypofractionated MR-guided RT with 1.5 T MRL is dosimetrically feasible for patients with prostate cancer. The improved soft tissue contrast and the online adaptive plan for 1.5 T MR-Linac allows for PTV margin reduction resulted in a significant dose reduction in OARs., (© 2023 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background: To evaluate the treatment outcomes and toxicity of definitive radiotherapy (RT) for prostate cancer (PC) patients using the simultaneous integrated boost (SIB) technique, which delivered 78 Gy to the entire prostate and 86 Gy to the intraprostatic lesion (IPL) in 39 fractions., Materials and Methods: 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., Results: The median follow-up for entire cohort was 68.5 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, Gleason score (GS), clinical nodal stage, and D'Amico risk group. Only 45 patients (7.3%) developed disease recurrence 41.9 months after RT. 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. 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 and transurethral resection independently predicted late Grade 2 GU toxicity, but no significant predictor of late Grade ≥2 GI toxicity was found., Conclusions: 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., (© 2023 Wiley Periodicals LLC.)

Purpose: We assessed early changes in apparent diffusion coefficient (ADC) and serum prostate specific antigen (PSA) values after definitive radiotherapy (RT) without androgen deprivation treatment in low- and intermediate-risk prostate cancer (PC) patients., Materials and Methods: The clinical data and ADC parameters of 229 PC patients were retrospectively evaluated. Pre-treatment and post-treatment serum PSA and primary tumor ADC values were calculated. Post-treatment DW-MRI was performed median 4.1 months after completion of definitive RT. The prognostic factors predicting freedom from biochemical failure (FFBF) and progression-free survival (PFS) were analyzed using univariable and multivariable analyses., Results: With a median follow-up time of 80.8 months, the 5-year FFBF and PFS rates were 95.9% and 89.3%, respectively. Eleven patients (4.8%) had PSA relapse, with a median of 34.4 months after the completion of RT. A statistically significant difference in post-treatment ADC values was noted between patients with and without recurrence (0.94 ± 0.07 vs. 1.10 ± 0.20 × 10 -3 mm 2 /sec; p< 0.001). Patients with a Gleason score (GS) of 6 and low-risk disease had significantly higher post-treatment tumor ADC and PSA levels than patients with a GS of 7 and intermediate-risk disease. The 5-year FFBF rate in patients with tumor ADC ≤ 0.96 × 10 -3 mm 2 /sec was significantly lower than patients with tumor ADC > 0.96 × 10 -3 mm 2 /sec (85.5% vs. 100; p< 0.001). In the multivariable analysis, a lower ADC value, GS 4 + 3 and intermediate-risk disease were independent predictors of worse FFBF. In the multivariate analysis, a lower post-treatment ADC value and a GS of 4 + 3 were significant prognostic factors for a lower PFS., Conclusion: These findings suggest that the post-treatment tumor ADC value could be used for early treatment response evaluation after definitive RT in PC patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: This study aimed to evaluate the safety and efficacy of ultra-hypofractionated stereotactic body radiation therapy (SBRT) to prostate bed., Methods: Sixty-six prostate cancer patients treated with postoperative ultra-hypofractionated SBRT between 2018 and 2020 were retrospectively reviewed. All patients received a total dose of 35 Gy to prostate bed in 5 fractions. Biochemical complete response (BCR), biochemical failure (BF), acute and late toxicities were assessed., Results: After a median follow-up of 24.2 months (range, 6.4-37.2), seven patients (10.6%) developed BF, and the 2-year freedom from BF (FFBF) rate was 88.4%. BCR was observed in 57 patients (86.4%). The 2-year FFBF in patients with pre-SBRT PSA value of <0.2 ng/mL was higher than those with pre-SBRT PSA of ≥0.2 ng/mL (100% vs. 81.4%; P = 0.04). The 2-year FFBF in patients with BCR was significantly higher than in those without BCR (94.5% vs. 58.3%; P < 0.001). In multivariate analysis, pre-SBRT PSA and post-SBRT PSA values were prognostic factors for FFBF (P = 0.009 and P = 0.01, respectively). Nine patients (13.6 %) developed acute and late grade 2 genitourinary (GU) toxicities. There was no acute or late grade ≥3 GU toxicity. Acute and late grade ≥2 gastrointestinal (GI) toxicity was observed in 9 (13.6%) and 2 (3%) patients, respectively., Conclusion: Postoperative ultra-fractionated SBRT showed no severe acute toxicity and late toxicity rates of about 15%, in addition to excellent biochemical control rates. Pre- and post-SBRT PSA levels may be a predictor of BCR in patients receiving post-operative ultra-fractionated SBRT., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To assess the correlation between initial tumor apparent diffusion coefficient (ADC) values and clinicopathological parameters in prostate cancer (PCa) patients treated with definitive radiotherapy (RT). Additionally, the prognostic factors for freedom from biochemical failure (FFBF) and progression-free survival (PFS) in this patient cohort were analyzed., Materials and Methods: The clinical data of 503 patients with biopsy-confirmed PCa were evaluated retrospectively. All patients had clearly evident tumors on diffusion-weighted magnetic resonance imaging (DW-MRI) for ADC values. Univariable and multivariable analyses were used to determine prognostic factors for FFBF and PFS., Results: The median follow-up was 72.9 months. The 5-year FFBF and PFS rates were 93.2% and 86.2%, respectively. Significantly lower ADC values were found in patients with a high PSA level; advanced clinical stage; higher ISUP score, and higher risk group than their counterparts. Receiver operating characteristic (ROC) curve analysis revealed an ADC cut-off value of 0.737 × 10 -3  mm 2 /sec for tumor recurrence. Patients who progressed had a lower mean ADC value than those who did not (0.712 ± 0.158 vs. 1.365 ± 0.227 × 10 -3  mm 2 /sec; p < 0.001). There was a significant difference in 5-year FFBF (96.3% vs. 90%; p < 0.001) and PFSrates (83.8% vs. 73.5%; p = 0.002) between patients with higher and lower mean ADC values. The FFBF and PFS were found to be correlated with tumor ADC value and ISUP grades in multivariable analysis. Additionally, older age was found to be a significant predictor of worse PFS., Conclusions: Lower ADC values were found in patients with high-risk characteristics such as a high serum PSA level, stage or grade of tumor, or high-risk disease, implying that ADC values could be used to predict prognosis. Lower ADC values and higher ISUP grades were associated with an increased risk of BF and progression, implying that treatment intensification may be required in these patients., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: We assessed the outcomes of stereotactic body radiotherapy (SBRT) to treat oligoprogressive castration-resistant prostate cancer (CRPC) patients with ≤5 lesions using gallium prostate-specific membrane antigen-positron emission tomography ( 68 Ga-PSMA-PET/CT)., Methods: The clinical data of 67 CRPC patients with 133 lesions treated with 68 Ga-PSMA-PET/CT-based SBRT were retrospectively analyzed. All of the patients had oligoprogressive disease during androgen-deprivation therapy (ADT). The prognostic factors for overall- (OS) and progression-free survival (PFS) and the predictive factors for switching to next-line systemic treatment (NEST) and NEST-free survival (NEST-FS) were analyzed., Results: With a median follow-up of 17.5 months, the 2-year overall survival (OS) and PFS rates were 86.9% and 34.4%, respectively. The PSA response was observed in 49 patients (73.1%). Progression was observed in 37 patients (55.2%) at a median of 11.0 months following SBRT. A total of 45 patients (67.2%) remained on ADT after SBRT, and 22 patients (32.8%) had a NEST change at a median of 16.4 months after metastasis-directed treatment (MDT). Patients with a NEST change had higher post-SBRT PSA values and fewer PSA nadirs after MDT than their counterparts. In multivariate analysis, higher pre-SBRT PSA values were the only significant predictor for worse OS and NEST-FS, and no significant factor was found for PFS. No serious acute or late toxicities were observed., Conclusion: This study demonstrated the feasibility of MDT using SBRT to treat oligoprogressive lesions by 68 Ga-PSMA-PET/CT in CRPC patients is efficient and well-tolerated, prolonging the effectiveness of ADT by delaying NEST., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Defining the extent of disease spread with imaging modalities is crucial for therapeutic decision-making and definition of treatment. This study aimed to investigate whether clinical parameters and nomograms predict prostate-specific membrane antigen (PSMA)-positive lymph nodes in treatment-naïve nonmetastatic prostate cancer (PC) patients., Materials and Methods: The clinical data of 443 PC patients (83.3% high-risk and 16.7% intermediate-risk) were retrospectively analyzed. Receiver operating characteristic (ROC) curves with areas under the curve (AUC) were generated to evaluate the accuracy of clinical parameters (prostate-specific antigen [PSA], T stage, Gleason score [GS], International Society of Urological Pathology [ISUP] grade) and nomograms (Roach formula [RF], Yale formula [YF], and a new formula [NF]) in predicting lymph node metastasis. The AUCs of the various parameters and clinical nomograms were compared using ROC and precision-recall (PR) curves., Results: A total of 288 lymph node metastases were identified in 121 patients (27.3%) using 68 Ga-PSMA-11-positron emission tomography (PET)/computed tomography (CT). Most PSMA-avid lymph node metastases occurred in external or internal iliac lymph nodes (142; 49.3%). Clinical T stage, PSA, GS, and ISUP grade were significantly associated with PSMA-positive lymph nodes according to univariate logistic regression analysis. The PSMA-positive lymph nodes were more frequently detected in patients with PSA >20 ng/ml, GS ≥7 or high risk disease compared to their counterparts. The clinical T stage, serum PSA level, GS, and ISUP grade showed similar accuracy in predicting PSMA-positive metastasis, with AUC values ranging from 0.675 to 0.704. The median risks for PSMA-positive lymph nodes according to the RF, YF, and NF were 31.3% (range: 12.3%-100%), 22.3% (range: 4.7%-100%), and 40.5% (range: 12.3%-100%), respectively. The AUC values generated from ROC and PR curve analyses were similar for all clinical nomograms, although the RF and YF had higher accuracy compared to NF., Conclusion: The clinical T stage, PSA, GS, and ISUP grade are independent predictors of PSMA-positive lymph nodes. The RF and YF can be used to identify patients who can benefit from 68 Ga-PSMA-11 PET/CT for the detection of lymph node metastasis. Together with nomograms, 68 Ga-PSMA-11 PET/CT images help to localize PSMA-positive lymph node metastases and can thus assist in surgery and radiotherapy planning., (© 2021 Wiley Periodicals LLC.)

Purpose: To evaluate the outcomes of metastasis-directed treatment (MDT) using stereotactic body radiotherapy (SBRT) for bone-only oligometastasis (OM) detected with gallium prostate-specific membrane antigen (68Ga-PSMA) PET/CT in castration-sensitive prostate cancer (PC) patients., Methods: In this multi-institutional study, clinical data of 74 PC patients with 153 bone lesions who were undergoing MDT were retrospectively evaluated. Twenty-seven patients (36.5%) had synchronous, and 47 (63.5%) had metachronous OM. All patients had PC with 5 metastases or fewer detected by 68Ga-PSMA PET/CT and treated using SBRT with a median dose of 20 Gy. The prognostic factors for PC-specific survival (PCSS) and progression-free survival (PFS) were analyzed., Results: The median follow-up was 27.3 months. Patients with synchronous OM were older and received higher rates of androgen deprivation therapy after SBRT compared with patients with metachronous OM. The 2-year PCSS and PFS rates were 92.0% and 72.0%, respectively. A prostate-specific antigen (PSA) decline was observed in 56 patients (75.7%), and 48 (64.9%) had a PSA response defined as at least 25% decrease of PSA after MDT. The 2-year local control rate per lesion was 95.4%. In multivariate analysis, single OM and PSA response after MDT were significant predictors for better PCSS and PFS. In-field recurrence was observed in 4 patients (6.5%) with 10 lesions at a median of 13.1 months after MDT completion. No serious late toxicity was observed., Conclusions: We demonstrated that SBRT is an efficient and well-tolerated treatment option for PC patients with 5 bone-only oligometastases or fewer detected with 68Ga-PSMA PET/CT., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study was to evaluate the outcomes of 68 Ga prostate-specific membrane antigen ( 68 Ga-PSMA) positron-emission tomography (PET)/CT-based metastasis-directed treatment (MDT) for oligometastatic prostate cancer (PC)., Methods: In this multi-institutional study, clinical data of 176 PC patients with 353 lesions receiving MDT between 2014 and 2019 were retrospectively evaluated. All patients had biopsy proven PC with ≤5 metastases detected with 68 Ga-PSMA-PET/CT. MDT was delivered with conventional fractionation or stereotactic body radiotherapy (SBRT) techniques. CTCAE v4.0 was used for acute and RTOG/EORTC Late Radiation Morbidity Scoring Schema was used for late toxicity evaluation., Results: At the time of MDT, 59 patients (33.5%) had synchronous and 117 patients (66.5%) had metachronous metastases. Median number of metastases was one and the MDT technique was SBRT in 73.3% patients. The 2‑year overall survival (OS) and progression-free survival (PFS) rates were 87.6% and 63.1%, respectively. With a median follow-up of 22.9 months, 9 patients had local recurrence at the irradiated site. The 2‑year local control rate at the treated oligometastatic site per patient was 93.2%. In multivariate analysis, an increased number of oligometastases and untreated primary PC were negative predictors for OS; advanced clinical tumor stage, untreated primary PC, BED3 value of ≤108 Gy, and MDT with conventional fractionation were negative predictors for PFS. No patient experienced grade ≥3 acute toxicity, but one patient had a late grade 3 toxicity of compression fracture after spinal SBRT., Conclusion: 68 Ga-PSMA-PET/CT-based MDT is an efficient and safe treatment for oligometastatic PC patients. Proper patient selection might improve treatment outcomes.

Purpose: To evaluate the distribution of metastatic lymph nodes (LN) detected on 68 Ga-PSMA-positron emission tomography/computed tomography (PET/CT) in treatment-naïve prostate cancer (PC) patients and to analyze the LN coverage rates of the pelvic fields defined in the GETUG trial and RTOG guidelines and a pelvic field extending superiorly from the L4/L5 interspace., Materials and Methods: 68 Ga-PSMA-PET/CT images obtained at diagnosis of 138 PC patients were retrospectively analyzed. The number and locations of 68 Ga-PSMA-positive LNs were co-registered with one single-planning CT. The numbers, locations, and sizes of LNs located outside the three pelvic volumes were investigated for the entire cohort and for patients with LN metastasis in the pelvic area only., Results: A total of 441 PSMA-PET-positive LN metastases were identified. The most frequent metastatic LNs were internal iliac LNs (25.2%). Para-aortic and presacral LNs outside the three pelvic fields were present in 20 (14.5%) and 22 patients (15.9%), respectively. The LN coverage rates according to the GETUG trial, the RTOG guidelines, and the pelvic field extending superiorly from L4/L5 were 44.2%, 52.2%, and 71, respectively, in the entire cohort and 51.7%, 61 and 83.1%, respectively, in patients with only pelvic LN metastasis. The number of metastatic LNs was a predictive factor for LNs located outside the three pelvic fields., Conclusions: Extending the cranial margin of the pelvic field from L5/S1 to L4/L5 increases the accuracy of pelvic field irradiation in approximately 20% of patients, highlighting the importance of proximal common iliac irradiation, particularly in patients with multiple LN metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: To compare the incidental testicular doses during volumetric-modulated arc therapy (VMAT) in patients receiving prostate-only and pelvic lymphatic irradiation., Materials and Methods: Testicular doses in 40 intermediate- and high-risk prostate cancer patients were determined on treatment planning system (TPS) using the VMAT technique at 6 MV. Scattered testicular doses were also measured by MOSFET detectors placed on testis surface. The testicular doses of patients treated with prostate-only and pelvic field irradiation were compared., Results: The median testicular doses measured per 200 cGy fraction by TPS and MOSFET detectors were 1.7 cGy (0.7-4.1 cGy) and 4.8 cGy (3.6-8.8 cGy), respectively. The TPS doses and MOSFET readings showed a significant strong correlation (Pearson r = 0.848, p < 0.001). The testicular doses measured by TPS (1.34 ± 0.36 cGy vs. 2.60 ± 0.95 cGy; p < 0.001) and MOSFET (4.52 ± 0.64 cGy vs. 6.56 ± 1.23 cGy; p < 0.001) were significantly lower in patients with prostate-only irradiation than in those with pelvic field irradiation. The mean cumulative scattered dose for prostate-only field delivering 78 Gy was 1.8 Gy and that for pelvic field irradiation was 2.6 Gy, consistent with the reported findings., Conclusions: The patients with prostate-only irradiation received lower testicular doses than those with additional pelvic field irradiation possibly due to the increased scattered doses in large field irradiation using the VMAT technique. The clinical response to increased incidental testicular doses due to pelvic field irradiation remains unknown, and it warrants further investigation.

Objective: The aim of the study is to investigate the correlation between the intensity of prostate-specific membrane antigen (PSMA) uptake in primary tumor and clinico-pathological characteristics of non-metastatic prostate cancer patients treated with definitive radiotherapy (RT)., Methods: Using the clinical data of 201 prostate cancer patients who were referred for 68  Ga-PSMA-positron emission tomography (PET/CT) for staging and RT planning, we analyzed the correlations among intermediate- or high-risk disease based on Gleason score (GS), prostate-specific antigen (PSA) level, D'Amico risk group classification, and maximum standardized uptake (SUV max ) of primary tumor., Results: Primary tumor was visualized via 68  Ga-PSMA-PET/CT scan in 192 patients (95.5%). The median SUV max of primary tumor and metastatic lymph node were 13.2 (range 3.3-83.7) and 11.4 (range 3.6-64.5), respectively. A significant moderate correlation was observed between PSA level and median tumor SUV max as measured by 68  Ga-PSMA-PET/CT (Spearman = 0.425; p < 0.001). Patients with serum PSA > 10 ng/mL, GS > 7, D'Amico high-risk group classification, and pelvic lymph node metastasis had significantly higher tracer uptake in primary tumor than their counterparts. The median SUV max of primary tumor was highest in patients with GS 9. The primary tumor detection rates of 68  Ga-PSMA-PET/CT were 83%, 92%, and 99% for patients with serum PSA ≤ 5.0 ng/mL (14 patients, 7%), PSA 5.1-10.0 ng/mL (45 patients, 22%), and PSA > 10 ng/mL (142 patients, 71%), respectively., Conclusions: We demonstrated a correlation between prostate tumor characteristics and PSMA tracer uptake. Patients with serum PSA > 10 ng/mL, GS > 7, D'Amico high-risk group classification, and pelvic lymph node metastasis had significantly higher SUV than their counterparts. In addition, the primary tumor detection rate was higher in patients with serum PSA > 10 ng/mL and GS > 7.

Purpose: To evaluate the effect of neoadjuvant androgen deprivation treatment (ADT) on prostate-specific membrane antigen (PSMA) tracer uptake demonstrated in 68 Ga-PSMA-positron emission tomography (PET/CT) in non-metastatic hormone-naïve prostate cancer (PC) patients., Materials and Methods: The clinical data of 108 PC patients who received neoadjuvant ADT were retrospectively analyzed. All patients had a baseline 68 Ga-PSMA-PET/CT scan, and a second scan was delivered median of 2.9 months after the initiation of ADT. The maximum standardized uptake value (SUV max ) of primary tumor (SUV p ) and metastatic lymph nodes (SUV ln ) as well as PSA response were assessed between pre- and post-ADT 68 Ga-PSMA-PET/CT scans., Results: There were significant decreases in posttreatment serum PSA, SUV p , and SUV ln . A decrease in SUV p was seen in 91 patients (84%) with a median value of 66% (range, 5-100%), while 17 patients (16%) had no change in or an increase in PSMA tracer uptake with a median value of 24% (range, 0-198%). Patients with Gleason score (GS) of 7 had significantly higher metabolic response rates compared to other patients. The disease progression was significantly higher only in patients with GS > 7 disease compared to GS 7 disease. The PSA response to ADT was the lowest in patients with ISUP high-grade tumors. A total of 16 patients (15%) had progressive disease, and in 9 patients (8%), radiotherapy decisions were modified according to posttreatment 68 Ga-PSMA-PET/CT scans., Conclusions: The current study includes the largest number of patients analyzed to date and demonstrates that ADT causes a significant decrease in serum PSA values and SUV p and SUV ln . The authors demonstrate that 68 Ga-PSMA-PET/CT may be used as a quantitative imaging modality after neoadjuvant ADT in hormone-naïve non-metastatic PC patients.

Purpose: To validate the clinical outcomes and prognostic factors in prostate cancer (PCa) patients with Gleason score (GS) 8-10 disease treated with external beam radiotherapy (EBRT) + androgen deprivation therapy (ADT) in the modern era., Methods: Institutional databases of biopsy proven 641 patients with GS 8-10 PCa treated between 2000 and 2015 were collected from 11 institutions. In this multi-institutional Turkish Radiation Oncology Group study, a standard database sheet was sent to each institution for patient enrollment. The inclusion criteria were, T1-T3N0M0 disease according to AJCC (American Joint Committee on Cancer) 2010 Staging System, no prior diagnosis of malignancy, at least 70 Gy total irradiation dose to prostate ± seminal vesicles delivered with either three-dimensional conformal RT or intensity-modulated RT and patients receiving ADT., Results: The median follow-up time was 5.9 years (range 0.4-18.2 years); 5‑year overall survival (OS), biochemical relapse-free survival (BRFS) and distant metastases-free survival (DMFS) rates were 88%, 78%, and 79%, respectively. Higher RT doses (≥78 Gy) and longer ADT duration (≥2 years) were significant predictors for improved DMFS, whereas advanced stage was a negative prognosticator for DMFS in patients with GS 9-10., Conclusions: Our results validated the fact that oncologic outcomes after radical EBRT significantly differ in men with GS 8 versus those with GS 9-10 prostate cancer. We found that EBRT dose was important predictive factor regardless of ADT period. Patients receiving 'non-optimal treatment' (RT doses <78 Gy and ADT period <2 years) had the worst treatment outcomes.

To assess the role of Gallium-labeled-prostate-specific membrane antigen PET/CT (Ga-PSMA-PET/CT) in risk group definition and radiotherapy planning in the initially planned definitive radiotherapy (RT) for prostate cancer patients., Methods: The clinical data of 191 prostate cancer patients treated with definitive intensity-modulated RT were retrospectively analyzed. All patients were initially staged with thoracoabdominal CT and bone scintigraphy, and the second staging was performed using Ga-PSMA-PET/CT. Both stages were evaluated for the decision making of RT and any change in RT target volumes., Results: After staging with Ga-PSMA-PET/CT, 26 patients (13.6%) had risk group changes, 16 patients (8.4%) had an increase in risk group, and 10 patients (5.2%) had a decrease in risk group. Down-staging occurred in 22 patients (11.5%), and upstaging was observed in 30 patients (15.7%). A total of 26 patients (13.6%) had nodal stage changes. After the Ga-PSMA-PET/CT scans, the number of metastatic patient increased to 17 (8.9%), with 4 of them moving from oligo- to polymetastatic disease. An additional irradiation of pelvic lymphatics and metastatic site was performed in 13 patients (6.8%) and 6 patients (3.2%), respectively. The RT was aborted in 4 patients (2.1%) because of parenchymal or distant site metastasis observed in the Ga-PSMA-PET/CT., Conclusions: We found that Ga-PSMA-PET/CT causes considerable migration in stage, risk group, and RT field arrangements, especially in high-risk patients regardless of the GS and baseline prostate-specific antigen values alone. Ga-PSMA-PET/CT seems to have a great influence on RT decision making in prostate cancer patients.

Purpose: To determine whether setup errors during external beam radiation therapy (RT) for prostate cancer are influenced by the combination of androgen deprivation treatment (ADT) and RT., Materials and Methods: Data from 175 patients treated for prostate cancer were retrospectively analyzed. Treatment was as follows: concurrent ADT plus RT, 33 patients (19%); neoadjuvant and concurrent ADT plus RT, 91 patients (52%); RT only, 51 patients (29%). Required couch shifts without rotations were recorded for each megavoltage (MV) cone beam computed tomography (CBCT) scan, and corresponding alignment shifts were recorded as left-right (x), superior-inferior (y), and anterior-posterior (z). The nonparametric Mann-Whitney test was used to compare shifts by group. Pearson's correlation coefficient was used to measure the correlation of couch shifts between groups. Mean prostate shifts and standard deviations (SD) were calculated and pooled to obtain mean or group systematic error (M), SD of systematic error (Σ), and SD of random error (σ)., Results: No significant differences were observed in prostate shifts in any direction between the groups. Shifts on CBCT were all less than setup margins. A significant positive correlation was observed between prostate volume and the z‑direction prostate shift (r = 0.19, p = 0.04), regardless of ADT group, but not between volume and x‑ or y‑direction shifts (r = 0.04, p = 0.7; r = 0.03, p = 0.7). Random and systematic errors for all patient cohorts and ADT groups were similar., Conclusion: Hormone therapy given concurrently with RT was not found to significantly impact setup errors. Prostate volume was significantly correlated with shifts in the anterior-posterior direction only.

Purpose: To compare soft-tissue cone-beam computed tomography (CBCT-P) and fiducial marker (CBCT-FM)-based image guided radiotherapy in prostate cancer patients., Materials and Methods: Sixteen prostate cancer patients were treated with volumetric modulated arc therapy. Manual alignment using CBCT-P and CBCT-FM was performed for each patient. Couch shifts were calculated and compared between methods in the left-right (x), superior-inferior (y), and anterior-posterior (z) directions., Results: CBCT-P and CBCT-FM alignments were compared using 252 scans from the 16 patients. Mean displacement from zero was 2.4 ± 1.3, 1.7 ± 1.2, and 1.8 ± 1.1 mm for CBCT-P and 2.3 ± 1.3, 1.7 ± 1.1 and 1.8 ± 1.1 mm for CBCT-FM in the x, y and z directions, respectively. There was no difference in median displacement between CBCT-P and CBCT-FM; however, there was a significant positive correlation between CBCT-P- and CBCT-FM-based displacements in the x (r = 0.881; p < 0.001), y (r = 0.789; p < 0.001) and z (r = 0.856; p < 0.001) directions by linear regression analysis. Systematic deviations within each group were <1 mm; however, random and systematic errors were similar in the x and y directions but larger in the z direction., Conclusion: Our study demonstrated that CBCT-FM was not superior to CBCT-P for image-guided radiotherapy in prostate cancer patients.

The aim of this study is to evaluate the incidental testicular doses during prostate radiation therapy with intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT) at different energies. Dosimetric data of 15 patients with intermediate-risk prostate cancer who were treated with radiotherapy were analyzed. The prescribed dose was 78Gy in 39 fractions. Dosimetric analysis compared testicular doses generated by 7-field intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy with a single arc at 6, 10, and 15MV energy levels. Testicular doses calculated from the treatment planning system and doses measured from the detectors were analyzed. Mean testicular doses from the intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy per fraction calculated in the treatment planning system were 16.3 ± 10.3cGy vs 21.5 ± 11.2cGy (p = 0.03) at 6MV, 13.4 ± 10.4cGy vs 17.8 ± 10.7cGy (p = 0.04) at 10MV, and 10.6 ± 8.5cGy vs 14.5 ± 8.6cGy (p = 0.03) at 15MV, respectively. Mean scattered testicular doses in the phantom measurements were 99.5 ± 17.2cGy, 118.7 ± 16.4cGy, and 193.9 ± 14.5cGy at 6, 10, and 15MV, respectively, in the intensity-modulated radiotherapy plans. In the volumetric-modulated arc radiotherapy plans, corresponding testicular doses per course were 90.4 ± 16.3cGy, 103.6 ± 16.4cGy, and 139.3 ± 14.6cGy at 6, 10, and 15MV, respectively. In conclusions, this study was the first to measure the incidental testicular doses by intensity-modulated radiotherapy and volumetric-modulated arc radiotherapy plans at different energy levels during prostate-only irradiation. Higher photon energy and volumetric-modulated arc radiotherapy plans resulted in higher incidental testicular doses compared with lower photon energy and intensity-modulated radiotherapy plans., (Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: To make dosimetric comparisons of volumetric-modulated arc therapy (VMAT) and 7-field intensity-modulated radiotherapy (IMRT) with dynamic MLCs using the Monaco treatment planning system with Monte Carlo algorithm., Materials and Methods: Single-arc VMAT and 7-field IMRT treatment plans were compared for 12 intermediate risk prostate cancer patients treated with prostate and seminal vesicle radiotherapy. For all patients, the prescribed dose was 78 Gy delivered in 39 fractions. The dosimetric data of IMRT and VMAT plans with 6, 10 and 15 MV energies were compared. The comparison was made for target volume, organs at risk (OAR) doses, and for monitor units (MU)., Results: The normal tissue surrounding the target were lower in VMAT plans compared to IMRT plans. VMAT plans achieved lower doses to all OARs for nearly all dosimetric endpoints. VMAT plans achieved 9.4, 9.0 and 7.0 % relative decrease in MUs required for RT delivery, for 6, 10 and 15 MV energy levels, respectively. The target volume and OAR dosimetric values did not differ significantly between 6, 10 and 15 MV photon energies., Conclusion: VMAT plans were found to be dosimetrically equivalent to IMRT plans for prostate cancer patients, with better rectum and bladder sparing and fewer MUs required.

Background: Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity., Material and Methods: Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25-30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed., Results: Mean age was 63 years (range: 43-81 years) and mean baseline citrulline concentration was 38.0 ± 10.1 μmol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 ± 5.9 μmol/l; p < 0.0001), treatment end (29.9 ± 8.8 μmol/l; p < 0.0001), and four months post-treatment (34.3 ± 12.1; p = 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent., Conclusion: Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity.

Background: To evaluate the impact of four different rectum contouring techniques and rectal toxicities in patients with treated with 3D conformal radiotherapy (3DCRT)., Methods: Clinical and dosimetric data were evaluated for 94 patients who received a total dose 3DCRT of 70 Gy, and rectal doses were compared in four different rectal contouring techniques: the prostate-containing CT sections (method 1); 1 cm above and below the planning target volume (PTV) (method 2); 110 mm starting from the anal verge (method 3); and from the anal verge to the sigmoid flexure (method 4). The percentage of rectal volume receiving RT doses (30-70 Gy) and minimum, mean rectal doses were assessed., Results: Median age was 69 years. Percentage of rectal volume receiving high doses (>or= 70 Gy) were higher with the techniques that contoured smaller rectal volumes. In methods 2 and 3, the percentage of rectal volume receiving >or= 70 Gy was significantly higher in patients with than without rectal bleeding (method 2: 30.8% vs. 22.5%, respectively (p = 0.03); method 3: 26.9% vs. 18.1%, respectively (p = 0.006)). Mean rectal dose was significant predictor of rectal bleeding only in method 3 (48.8 Gy in patients with bleeding vs. 44.4 Gy in patients without bleeding; p = 0.02)., Conclusion: Different techniques of rectal contouring significantly influence the calculation of radiation doses to the rectum and the prediction of rectal toxicity. Rectal volume receiving higher doses (>or= 70 Gy) and mean rectal doses may significantly predict rectal bleeding for techniques contouring larger rectal volumes, as was in method 3.

Objectives: To prospectively assess the efficacy and tolerability of bicalutamide monotherapy on biochemical failure of localized prostate cancer following total androgen deprivation (TAD) and 3D-conformal radiotherapy (3D-CRT)., Methods: Between January 1998 and January 2002, we prospectively evaluated 20 eligible patients with biochemical failure. All patients were initially treated with neoadjuvant TAD of 12 weeks before 3D-CRT (73.6 Gy at isocenter) and same regimen of TAD after completion of radiotherapy for 24 weeks in high-risk patients. We prescribed 150 mg/day bicalutamide monotherapy for 24 weeks in patients with biochemical failure according to American Society for Therapeutic Radiology and Oncology 1997 consensus definition. Primary end points were biochemical control (BC) and metastasis-free survival (MFS)., Results: Median follow-up was 28 months after biochemical failure date. At last visit, the median PSA level of all patients was 2.80 ng/dl while 1.28 ng/dl for nonmetastatic and 30.7 ng/dl for metastatic patients. BC was successfully obtained in five of them with only bicalutamide. Ten patients developed distant metastasis among 15 patients receiving salvage TAD. MFS was 55% at three years for all 20 patients. Temporary gynecomasty was observed in 11 patients as the only serious toxicity., Conclusions: Bicalutamide monotherapy seems to be a tolerable regimen for patients with biochemical failure following 3D-CRT, and TAD and may be effective in patients with low PSA levels at biochemical failure.