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Background: Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series., Materials and Methods: We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan-Meier survival curves and fitted univariate and multivariable Cox's proportional hazards regression models to study the association between the clinical variables and each survival type., Results: At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3-99.6%) and 85.5% (95%CI 81.9-89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4-6%) and 6% (95%CI 4-8%), respectively., Conclusion: Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials., (© 2024. The Author(s).)

Earlier treatment intensification with systemic potent androgen receptor inhibition has been shown to improve clinical outcomes in metastatic hormone sensitive prostate cancer. Nonetheless, oligometastatic patients may benefit from local treatment approaches such as stereotactic body radiotherapy (SBRT). Aiming to explore the benefit of SBRT in this scenario, we designed this trial to specifically test the hypothesis that SBRT will improve clinical outcomes in select population affected by metachronous oligometastatic HSPC treated with androgen deprivation therapy + apalutamide. Enrolled patients will be randomized to receive the standard systemic treatment alone or in combination with SBRT on all metastatic sites of disease. Here we report the protocol design and an overview of the ongoing trials testing different integration strategies between RT and systemic therapies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Up to 47% of patients with localized prostate cancer (PCa) treated with radiotherapy (EBRT) eventually develop local recurrence. To date, no clear consensus exists on optimal management. A growing body of interest supports the use of stereotaxic re-irradiation (rSBRT), with promising oncological outcomes and low toxicity profile. We collected a single-center case series of locally recurrent PCa who underwent re-irradiation after a previous course of postoperative or definitive radiotherapy., Methods and Materials: Data from 101 patients treated at our institution for locally recurrent PCa from June 2012 to June 2021 were retrospectively collected. Patients underwent rSBRT with CyberKnife system (Accuray Inc., Sunnyvale, CA, USA), delivered to intraprostatic or macroscopic recurrences within the prostate bed, for a total dose of 30 Gy in 5 fractions., Results: All patients received prior EBRT. The median EQD2 total dose was 75.0 Gy (range, 60-80 Gy). Thirty-two (32%) patients were receiving androgen deprivation therapy (ADT) after prior biochemical recurrence. After a median follow-up of 57.8 months, BR occurred in 55 patients (54.5%), with a median BR-free survival (BRFS) of 40.4 months (95% C.I. 34.3-58.3). Thirty-two patients (31.7%) developed metastatic disease, with a median metastasis-free survival (MFS) not reached. PSA ≥ 2.5 ng/ml and ADT were associated with worst BRFS (26.06 vs. 39.3 months, p = 0.03 and 22.7 vs. 27 months, p = 0.01, respectively). Castration-resistant status and ADT were found to be predictive of worst MFS (34.1 vs. 50.5 months, p = 0.02 and 33.5 vs. 53.1 months, p = 0.002, respectively). Concomitant ADT was confirmed as an independent factor for MFS (HR 4.8, 95% CI 1.5-10.6, p = 0.007). No grade > /2 adverse were recorded., Conclusions: After almost 5 years of follow-up, with a median BRFS of 40.4 months and no grade ≥ 2 AEs, Cyberknife R rSBRT proved effective and safe in a cohort of 101 patients affected by locally recurrent PCa., (© 2023. Italian Society of Medical Radiology.)

Background: M1a disease represents an intermediate status between loco-regional relapse and bone metastatic disease. Metastasis directed therapy (MDT), through stereotactic body RT (SBRT) may be offered to patients, aiming to exclusively treat sites of macroscopic relapse and avoiding wide prophylactic treatment volumes. This appears as a viable treatment, especially after the rise of PSMA tailored treatment approaches., Materials and Methods: Data about patients treated in two different institutions were retrieved from a prospectively collected dataset. All included patients were affected by oligo-recurrent M1a disease after definitive RT or radical prostatectomy, defined as ≤ 3 nodal lesions situated above aortic bifurcation and below renal arteries. Both castration resistant PCa (CRPC) and castration sensitive (CSPC) PCa patients were included. All imaging methods were allowed to detect recurrence (CT scan, Choline or PSMA PET/CT).All sites of recurrences were treated with SBRT., Results: Median PFS was 10 months (95% CI 8-17). Twelve patients died, with a median OS of 114 months (95% CI 85-114). Out of the 83 recurrences, 2 (2.4%), 11 (13.25%), 36 (43.37%) and 15 (18%) patients had respectively prostate bed only, pelvic nodal, para-aortic or distant relapse. Furthermore, 19 (22.9%) patients experienced a biochemical only relapse with negative imaging at re-staging., Discussion: MDT conferred a remarkable PFS outcome in a mixed cohort of CSPC and CRPC patients with m1a disease, with an optimal safety profile. Prospective trials are needed in order to compare MDT and ENRT for these patients, allowing to select the best treatment option., (© 2023. Italian Society of Medical Radiology.)

Background: Ultrasensitive imaging has been demonstrated to influence biochemical relapse treatment. PSICHE is a multicentric prospective study, aimed at exploring detection rate with 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and outcomes with a predefined treatment algorithm tailored to the imaging., Methods: Patients affected by biochemical recurrence after surgery (prostate specific antigen [PSA] > 0.2 < 1 ng/mL) underwent staging with 68Ga-PSMA PET/CT. Management followed this treatment algorithm accordingly with PSMA results: prostate bed salvage radiotherapy (SRT) if negative or positive within prostate bed, stereotactic body radiotherapy (SBRT) if pelvic nodal recurrences or oligometastatic disease, androgen deprivation therapy (ADT) if nonoligometastatic disease. Chi-square test was used to evaluate the relationship between baseline features and rate of positive PSMA PET/CT., Results: One hundred patients were enrolled. PSMA results were negative/positive in the prostate bed in 72 patients, pelvic nodal or extrapelvic metastatic disease were detected in 23 and 5 patients. Twenty-one patients underwent observation because of prior postoperative radiotherapy (RT)/treatment refusal. Fifty patients were treated with prostate bed SRT, 23 patients underwent SBRT to pelvic nodal disease, five patients were treated with SBRT to oligometastatic disease. One patient underwent ADT. NCCN high-risk features, stage > pT3 and ISUP score >3 reported a significantly higher rate of positive PSMA PET/CT after restaging (p = 0.01, p = 0.02, and p = 0.002). By quartiles of PSA, rate of positive PSMA PET/CT was 26.9% (>0.2; <0.29 ng/mL), 24% (>0.3; <0.37 ng/mL), 26.9% (>0.38; <0.51 ng/mL), and 34.7% (>0. 52; <0.98 ng/mL)., Conclusions: PSICHE trial constitute a useful platform to collect data within a clinical framework where modern imaging and metastasis-directed therapy are integrated., (© 2023 Wiley Periodicals LLC.)

PSICHE (NCT05022914) is a prospective trial to test a [ 68 Ga]Ga- PSMA-11 PET/CT imaging tailored strategy. All evaluable patients had biochemical relapse after surgery and underwent centralized [ 68 Ga]Ga-PSMA-11 PET/CT imaging. The treatment was performed according pre-defined criteria. Observation and re-staging at further PSA progression were proposed to patients with negative PSMA and previous postoperative RT. Prostate bed SRT was proposed to all patients with a negative staging or positive imaging within prostate bed. Stereotactic body radiotherapy (SBRT) to all sites of disease was used for all patients with pelvic nodal recurrence (nodal disease < 2 cm under aortic bifurcation) or oligometastatic disease. At 3 months after treatment, 54.7% of patients had a complete biochemical response Only 2 patients experienced G2 Genitourinary toxicity. No G2 Gastrointestinal toxicity was recorded. A PSMA targeted treatment strategy led to encouraging results and was well tolerated., (© 2023. The Author(s).)

Background: Patients who received a kidney transplant (KT) are described in literature as a group with a higher incidence of malignant neoplasms compared to the general population. Cancer development after KT has become a major issue, as a remarkable percentage of patients are diagnosed with cancer. Treatment of prostate cancer (PCa) in renal transplant recipients (RTRs) is a challenging issue that has been discussed by many authors over the years, but evidence is sparse and often includes conflicting reports. Among the therapeutic options for PCa in these patients, prostate irradiation represents a valuable alternative to surgery or other systemic therapies, as RTRs are often ineligible for these treatments., Objective: To report six cases treated at our institution between 1998 and 2017 and discuss the available literature., Methods: Patients' characteristics were reported along with biochemical status at diagnosis, type of immunosuppressive treatment, radiation therapy technique, and dose to transplanted kidney., Results: Overall, prostate irradiation was delivered respecting the dose constraints and patients showed good tolerance with no reports of acute or late transplanted kidney injury., Conclusions: Our experience confirms that prostate radiotherapy for RTRs is feasible and effective and represents a valid option that should be considered by the multidisciplinary team.

To assess the outcomes of a cohort of bone oligometastatic prostate cancer patients treated with PSMA-PET guided stereotactic body radiotherapy (SBRT). From April 2017 to January 2021, 40 patients with oligorecurrent prostate cancer detected by PSMA-PET were treated with SBRT for bone oligometastases. Concurrent androgen deprivation therapy was an exclusion criterion. A total of 56 prostate cancer bone oligometastases were included in the present analysis. In 28 patients (70%), oligometastatic disease presented as a single lesion, two lesions in 22.5%, three lesions in 5%, four lesions in 2.5%. 30.3% were spine-metastases, while 69.7% were non-spine metastases. SBRT was delivered for a median dose of 30 Gy (24-40 Gy) in 3-5 fractions, with a median EQD 2  = 85 Gy 2 (64.3-138.9Gy 2 ). With a median follow-up of 22 months (range 2-48 months), local control (LC) 1- and 2-years rates were 96.3% and 93.9%, while distant progression-free survival (DPFS) rates were 45.3% and 27%. At multivariate analysis, the lower PSA nadir value after SBRT remained significantly related to better DPFS rates (p = 0.03). In 7 patients, a second SBRT course was proposed with concurrent ADT, while 11 patients, due to polymetastatic spread, received ADT alone, resulting in 1- and 2-years ADT-free survival rates of 67.5% and 61.8%. At multivariate analysis, a lower number of treated oligometastases maintained a correlation with higher ADT-free survival rates (p = 0.04). In our experience, PSMA-PET guided SBRT resulted in excellent results in terms of clinical outcomes, representing a helpful tool with the aim to delay the start of ADT., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To assess outcomes between salvage radiation therapy (SRT) with curative intent and stereotactic radiotherapy for macroscopic prostate recurrence (SSRT) after radical prostatectomy (RP). In order to compare these two different options, we compared their outcomes with a propensity score-based matched analysis., Methods: Data from 185 patients in seven Italian centres treated for macroscopic prostate bed recurrence after RP were retrospectively collected. To make a comparison between the two treatment groups, propensity matching was applied to create comparable cohorts., Results: After matching, 90 patients in the SRT and SSRT groups were selected (45 in each arm). Kaplan-Meier analysis did not show any significant differences in terms of BRFS and PFS between matched populations (p = 0.08 and p = 0.8, respectively). Multivariate models show that treatment was not associated with BRFS, neither in the whole or matched cohort, with HR of 2.15 (95%CI 0.63-7.25, p = 0.21) and 2.65 (95%CI 0.59-11.97, p = 0.21), respectively. In the matched cohort, lower rate of toxicity was confirmed for patients undergoing SSRT, with acute GI and GU adverse events reported in 4.4 versus 44.4% (p < 0.001) and 28.9 versus 46.7% (p = 0.08) of patients, and late GI and GU adverse events reported in 0 versus 13.3% (p = 0.04) and 6.7 versus 22.2% (p = 0.03) of patients, respectively., Conclusion: Considering the favourable therapeutic ratio of this approach and the lower number of fractions needed, SSRT should be considered as an attractive alternative to conventional SRT in this setting., (© 2022. Italian Society of Medical Radiology.)

Purpose: Given the absence of standardized planning approach for clinically node-positive (cN1) prostate cancer (PCa), we collected data about the use of prophylactic pelvic irradiation and nodal boost. The aim of the present series is to retrospectively assess clinical outcomes after this approach to compare different multimodal treatment strategies in this scenario., Methods: Data from clinical records of patients affected by cN1 PCa and treated in six different Italian institutes with prophylactic pelvic irradiation and boost on pathologic pelvic lymph nodes detected with CT, MRI or choline PET/CT were retrospectively reviewed and collected. Clinical outcomes in terms of overall survival (OS) and biochemical relapse-free survival (b-RFS) were explored. The correlation between outcomes and baseline features (International Society of Urological Pathology-ISUP pattern, total dose to positive pelvic nodes ≤ / > 60 Gy, sequential or simultaneous integrated boost (SIB) administration and definitive vs postoperative treatment) was explored., Results: ISUP pattern < 2 was a significant predictor of improved b-RFS (HR = 0.3, 95% CI 0.1220-0.7647, P = 0.0113), while total dose < 60 Gy to positive pelvic nodes was associated with worse b-RFS (HR = 3.59, 95% CI 1.3245-9.741, P = 0.01). Conversely, treatment setting (postoperative vs definitive) and treatment delivery technique (SIB vs sequential boost) were not associated with significant differences in terms of b-RFS (HR = 0.85, 95% CI 0.338-2.169, P = 0.743, and HR = 2.39, 95% CI 0.93-6.111, P = 0.067, respectively)., Conclusion: Results from the current analysis are in keeping with data from literature showing that pelvic irradiation and boost on positive nodes are effective approaches. Upfront surgical approach was not associated with better clinical outcomes., (© 2021. Italian Society of Medical Radiology.)

Background and Purpose: Between 30% and 47% of patients treated with definitive radiotherapy (RT) for prostate cancer are at risk of intraprostatic recurrence during follow-up. Re-irradiation with stereotactic body RT (SBRT) is emerging as a feasible and safe therapeutic option. However, no consensus or guidelines exist on this topic. The purpose of this ESTRO ACROP project is to investigate expert opinion on salvage SBRT for intraprostatic relapse after RT., Materials and Methods: A 40-item questionnaire on salvage SBRT was prepared by an internal committee and reviewed by a panel of leading radiation oncologists plus a urologist expert in prostate cancer. Following the procedure of a Delphi consensus, 3 rounds of questionnaires were sent to selected experts on prostate re-irradiation., Results: Among the 33 contacted experts, 18 (54.5%) agreed to participate. At the end of the final round, participants were able to find consensus on 14 out of 40 questions (35% overall) and major agreement on 13 questions (32.5% overall). Specifically, the consensus was reached regarding some selection criteria (no age limit, ECOG 0-1, satisfactory urinary flow), diagnostic procedures (exclusion of metastatic disease, SBRT target defined on the MRI) and therapeutic approach (no need for concomitant ADT, consideration of the first RT dose, validity of Phoenix criteria for salvage SBRT failure)., Conclusion: While awaiting the results of ongoing studies, our ESTRO ACROP Delphi consensus may serve as a practical guidance for salvage SBRT. Future research should address the existing disagreements on this promising approach., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The present analysis aims to compare the impact of 18F-fluorocholine ( 18 F-choline) and gallium-68 prostate-specific membrane antigen ( 68 Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)-guided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC)., Materials and Methods: Inclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by 18 F-choline or 68 Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered., Results: A total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent 68 Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the 68 Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PET-guided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with 68 Ga-PSMA-based SBRT., Conclusion: In the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the 18 F-choline-PET cohort. Randomized trials are advocated., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recent findings from literature evidenced that metastatic prostate cancer often shows heterogeneous response to therapy, with persistent sensibility to systemic treatments after biochemical, clinical, or radiographic progression. This highlights the advantage of integrated approaches in which local ablative treatments (e.g., stereotactic body radiation therapy) could prolong clinical benefit of systemic therapies beyond oligo-progression. Of course, development of predictive biomarker could be helpful in order to select patients who could much benefit from this treatment strategy. Circulating tumor cell detection and analysis could also have a crucial role in this field. A joint effort of two prospective ongoing trials (ARTO, clinical.gov identifier NCT03449719 and PRIMERA, clinical.gov identifier NCT04188275) might help to improve criteria to select patients in whom a local ablative approach might confer significant benefit. In this commentary, we summarized recent data from literature to support this thesis.

Purpose: To adapt the management of prostate malignancy in response to the COVID-19 pandemic., Methods: In according to the recommendations of the European Association of Urology, we have developed practical additional document on the treatment of prostate cancer., Results: Low-Risk Group Watchful Waiting should be offered to patients >75 years old, with a limited life expectancy and unfit for local treatment. In Active Surveillance (AS) patients re-biopsy, PSA evaluation and visits should be deferred for up to 6 months, preferring non-invasive multiparametric-MRI. The active treatment should be delayed for 6-12 months. Intermediate-Risk Group AS should be offered in favorable-risk patients. Short-course neoadjuvant androgen deprivation therapy (ADT) combined with ultra-hypo-fractionation radiotherapy should be used in unfavorable-risk patients. High-Risk Group Neoadjuvant ADT combined with moderate hypofractionation should be preferred. Whole-pelvis irradiation should be offered to patients with positive lymph nodes in locally advanced setting. ADT should be initiated if PSA doubling time is < 12 months in radio-recurrent patients, as well as in low priority/low volume of metastatic hormone sensitive prostate cancer. If radiotherapy cannot be delayed, hypo-fractionated regimens should be preferred. In high priority class metastatic disease, treatment with androgen receptor-targeted agents should be offered. When palliative radiotherapy for painful bone metastasis is required, single fraction of 8 Gy should be offered., Conclusions: In Covid-19 Era, the challenge should concern a correct management of the oncologic patient, reducing the risk of spreading the virus without worsening tumor prognosis., (Copyright © 2021. Published by Elsevier Ltd.)

Cancer in the elderly remains an evolving issue and a health challenge. Several improvements in the radiotherapy field allow the delivery of higher doses/fractions with a safe toxicity profile, permitting the reduction of radiation treatment protocols in the elderly. Regarding breast, prostate, and lung cancer, the under-representation of older patients in clinical trials limits the extension of treatment recommendations to elderly patients in routine clinical practice. Among the feasible alternatives to standard whole breast radiotherapy (WBRT) in older patients are shorter courses using higher hypofractionation (HF) and accelerated partial breast irradiation (APBI). The boost continues to be used in women at high risk of local recurrence but is less widely accepted for women at lower risk and patients over 70 years of age. Regarding prostate cancer, there are no published studies with a focus on the elderly. Current management decisions are based on life expectancy and geriatric assessment. Regimens of HF and ultra-HF protocols are feasible strategies for older patients. Several prospective non-randomized studies have documented the safe delivery of ultra-HF for patients with localized prostate cancer, and multiple phase III trials and meta-analyses have confirmed that the HF regimen should be offered with similar acute toxicity regardless of patient age and comorbidity. A recent pooled analysis from two randomized trials comparing surgery to stereotactic body radiation therapy (SBRT) in older adult patients with early stage non-small cell lung cancer did show comparable outcomes between surgery and SBRT. Elderly cancer patients are significantly under-represented in all clinical trials. Thus, the inclusion of older patients in clinical studies should be strongly encouraged to strengthen the evidence base for this age group. We suggest that the creation of oncogeriatric coordination units may promote individualized care protocols, avoid overtreatment with aggressive and unrecommended therapies, and support de-escalating treatment in elderly cancer patients., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2020 Desideri I et al.)

Context: Different nonsurgical therapeutic strategies can be adopted for intraprostatic relapse of prostate cancer after primary radiotherapy, including re-irradiation (with brachytherapy [BT] or external beam radiotherapy [EBRT]), high-intensity focused ultrasound (HIFU), and cryotherapy. The main issues to consider when choosing nonsurgical salvage local therapies are local tumor control and significant genitourinary toxicity., Objective: To conduct a systematic review and meta-analysis of the role of nonsurgical salvage modalities in patients with radiorecurrent prostate cancer and associated clinical outcomes and toxicity profiles., Evidence Acquisition: We performed a critical review of the Medline, Scopus, and ClinicalKey databases from January 1, 2000 through February 1, 2018 according to the Preferred Reporting Items and Meta-Analyses statement. To assess the overall quality of the literature reviewed, we used a modified Delphi tool for case-series studies., Evidence Synthesis: A total of 64 case-series studies were included, corresponding to a cohort of 5585 patients. The modified Delphi checklist evidenced high methodological quality overall (mean quality score of 80.6%). Biochemical control rates were lowest for patients treated with HIFU (58%, 95% confidence interval [CI] 47-68%) and highest for patients treated with BT (69%, 95% CI 62-76%) and EBRT (69%, 95% CI 53-83%). The lowest prevalence of incontinence was for patients treated with BT (3%, 95% CI 0-6%; I 2 =63.4%) and the highest was among patients treated with HIFU (28%, 95% CI 19-38%; I 2 =89.7%)., Conclusions: Nonsurgical therapeutic options, especially BT, showed good outcomes in terms of biochemical control and tolerability in the local recurrence setting., Patient Summary: The current analysis demonstrated that nonsurgical salvage local therapies offer a chance of a curative local approach in radiorecurrent prostate cancer. However, high-quality data from prospective trials are needed to validate long-term outcomes from nonsurgical strategies for the treatment of intraprostatic recurrence after previous radiotherapy., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the safety and effectiveness of stereotactic salvage radiotherapy (SSRT) in RT-naïve patients affected by macroscopic prostate bed recurrence., Patients and Methods: Consecutive patients treated for prostate bed macroscopic recurrence in three different Italian institutes were reviewed. Patients were treated with SSRT, with a total dose of 30-40 Gy in five fractions, the mean pre-SSRT PSA level was 2.3 ng/mL. Two different PSA thresholds were defined and biochemical recurrence-free survival (BCRFS) was reported, in order to better express outcome: BCRFS1 (a PSA level increase of >10% compared to the pre-SSRT value) and BCRFS2 (a PSA level increase of >0.2 ng/mL for patients with a PSA nadir of <0.2 ng/mL or two consecutive PSA level increases of >25% compared to nadir in patients with a PSA nadir of <0.2 ng/mL)., Results: In all, 90 patients were treated, with a mean (range) follow-up of 21.2 (2-64) months, and 17 of these patients (19%) had concomitant androgen-deprivation therapy (ADT) during SSRT. Complete biochemical response, defined as a PSA nadir of <0.2 ng/mL, was obtained in 39 of the 90 patients (43.3%). Considering BCRFS1, 25 patients (27.8%) had BCR, with an actuarial median BCRFS1 time of 36.4 months. For BCRFS2, BCR was reported in 32 patients (35.5%), with an actuarial median BCRFS2 time of 24.3 months. There was no Grade >2 toxicity., Conclusions: SSRT was found to yield significant biochemical control and allowed ADT delay despite adverse features., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Prostatectomy, radiotherapy and watchful waiting are the main therapeutic options available for local stage of prostate cancer (PCa). We report our experience on 394 patients affected by prostate cancer primarily treated with high-dose, image-guided, IMRT, focusing on gastrointestinal, genitourinary toxicities and biochemical control., Methods: From July 2003 to August 2014, 394 patients were treated with radical high-dose radiotherapy (HDRT) for prostate cancer; the mean total radiation dose was 79 Gy in standard fractions. Hormonal therapy (HT) was administered to 7.6% of low-risk patients, to 20.3% of intermediate-risk patients and to 72% of high-risk patients. Patients were evaluated for biochemical failure, local recurrence (LR) and metastases., Results: Ninety-seven patients (26.65%) developed acute GU toxicity at the medium dose of 25.4 Gy, grade 1 (G1) or grade 2 (G2) in 94 cases. Only 16 patients (4.06%) reported chronic GU toxicity (G1 or G2), and one case developed G3 cystitis. No G3 GI acute and late toxicity were detected. Fifty-six (14.2%) patients experienced LR, 26 (6.6%) developed metastases and 70 patients (17.8%) were deceased. Gleason sum score > 7 was predictive for worse overall survival (GS = 7 was borderline) and for metastasis. No factors resulted predictive for local relapse. HT pre-RT had been demonstrated as a negative predictor for OS and DFS-DM., Conclusions: Data confirm the safety of HDRT for PCa. Treatment was efficient with low toxicity profile. Moreover, continued technologic advancements, as image-guided radiotherapy, could lead to further reduction in toxicity, thus increasing the therapeutic index.

Background: Whole pelvic irradiation in prostate cancer patients might prevent metastatic spread of cancer cells through lymphatic drainages in patients eligible for definitive radiotherapy, but its use has declined in the last decades in favor of prostate-only irradiation (POI). The aim of our study is to assess the incidence of pelvic lymph nodal relapse and outcome in prostate cancer patients receiving POI., Materials and Methods: Data from 207 consecutive patients were collected. Clinical and treatment variables were collected. Biochemical relapse-free survival (BRFS), pelvic nodal relapse-free survival (PNRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) were calculated; analysis of prognostic variables was performed., Results: Five-year BRFS, PNRFS, DMFS, DSS and OS were, respectively, 90, 98, 96, 97 and 91%. On multivariate analysis, independent negative predictors of BRFS were Gleason score ≥ 7 (HR: 3.25) and PSA nadir ≥ 0.08 (HR: 4.86). Pelvic nodal relapse was not correlated to impaired outcome., Conclusions: Lymph nodal pelvic relapse occurs in 2% of patients at 5 years and does not correlate with impaired outcome, suggesting the lack of theoretical benefit of a prophylactic nodal irradiation. Tumor biology and response to treatment are the main determinants of outcome.

Background: Stereotactic body radiotherapy (SBRT) emerged as a treatment option in oligometastatic (≤3 metastases) patients experiencing lymph node relapse from treated prostate cancer. No recommendations are available concerning dose schedule, and available studies report the use of multiple-fraction regimens due to theoretical lower toxicity and higher cumulative dose delivered to the target. The aim of the present study was to evaluate the safety and efficacy of a dose-intensive, single-fraction SBRT regimen., Patients and Methods: Retrospective data on outcome and toxicity from 27 treatments on 23 consecutive patients were collected. Statistical analysis was performed., Results: Median follow-up was 22 months (range 6-63, interquartile range 15-28). Biochemical progression-free survival (bPFS) at 6 months, 1 year, and 2 years were 65%, 40%, and 26%, respectively. In 2 cases acute toxicity of grade 1 were observed., Conclusion: Single-fraction SBRT for lymph node relapse of oligometastatic prostate cancer resulted in promising biochemical control with minimal toxicity., (© 2018 S. Karger GmbH, Freiburg.)

Background: After radiotherapy (RT) for prostate cancer (PCa), several patients reported lower urinary tract symptoms (LUTS) due to damage and discontinuation of the glycosaminoglycan layer of the bladder. Instillation of hyaluronic acid and chondroitin sulfate (HA-CS) represents replenishment therapy of the glycosaminoglycan layer. The aim of the study is to evaluate the efficacy and safety of HA-CS in men with symptomatic cystitis after RT for PCa., Materials and Methods: Eighty consecutive men were treated with RT for PCa; 30 of these (37.5%) reported clinically relevant LUTS and associated bother as measured by the Interstitial Cystitis Symptom Index and Problem Index (ICSI/ICPI) Questionnaire 3 months after RT. Symptomatic patients received instillation therapy with HA-CS weekly for the first month and then at weeks 6, 8, and 12. All patients completed the ICSI/ICPI questionnaire before and after RT and at the end of HA-CS treatment., Results: HA-CS significantly reduced postradiation LUTS (P < .001) and bother (P = .006). Age, Gleason score, and radiation dose were the main determinants of worsening of LUTS after radiation (ICSI score baseline vs. postradiation: P = .047, .043, and .023). In multivariate analysis, only age influenced LUTS worsening after RT (P = .01). Age, radiation dose, and radiation toxicity were related to recovery of LUTS (ICSI score postradiation vs. post-HA-CS P = .041, P = .050, and P = .046). In multivariate analysis, no factor was statistically significant., Conclusions: A remarkable worsening of symptoms and bother was observed after RT. HA-CS instillation is a safe treatment and resulted in an improvement of LUTS irrespective of age and clinical features, with full recovery of urinary bother., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to identify prostate-specific antigen (PSA) kinetics parameters predictive of [(18)F]fluorocholine positron emission tomography/computed tomography ((18)FC PET/CT) features worsening in a cohort of patients with biochemical failure after prostate cancer treatment., Material and Methods: This longitudinal cohort study comprised 103 consecutive patients. All patients underwent two (18)FC PET/CT scans: one at baseline (PET1) and one after 6 months (PET2). Total PSA (tPSA), PSA velocity (vPSA), PSA doubling time (PSAdt), absolute variation in PSA values between PET2 and PET1 (ΔPSA), and percentage variation in PSA between the two PSA measurements (PSA%) were measured in each patient. Progression of disease on (18)FC PET/CT findings was compared with the PSA kinetics parameters. The major outcome measure was disease progression at PET2., Results: (18)FC PET/CT progression between PET1 and PET2 was reported in 64 patients (62.1%), while in 39 cases it remained unvaried. The following PSA kinetic parameters correlated with worsened (18)FC PET/CT findings: ΔPSA >5 ng/ml [odds ratio (OR = 6.44, 95% confidence interval (CI) 1.04-39.6; p = 0.04], vPSA >6 ng/ml/month (OR = 5.2, 95% CI 0.9-29.8; p = 0.05) and PSAdt <6 months (OR = 5.2, 95% CI 0.4-5.4; p = 0.03). From receiver operating characteristics (ROC) analysis, the combination with the three PSA kinetics parameters for predicting worsened (18)FC PET/CT findings resulted in a sensitivity of 86% (95% CI 77-92%) and specificity of 77% (95% CI 65-85%)., Conclusion: PSA kinetics is strictly related to (18)FC PET/CT findings. In patients with biochemical relapse, ΔPSA >5 ng/ml, PSAdt <6 months and vPSA >6 ng/ml/month are highly predictive of (18)FC PET/CT features worsening, independently from the treatment received.

Purpose: Radiotherapy (RT) has an established role in the treatment of prostate cancer patients. Despite the large number of patients treated with RT, some issues about optimal techniques, doses, volumes, timing, and association with androgen deprivation are still subject of debate. The aim of this survey was to determine the patterns of choice of Italian radiation oncologists in two different clinical cases of prostate cancer patients treated with radical RT., Study Design: During the 2010 Italian Association of Radiation Oncology (AIRO) National congress, four different clinical cases were presented to attending radiation oncologists. Two of them were prostate cancer cases that could be treated by RT +/- hormonal therapy (HT), different for T stage of primary tumour according to TNM, preoperative diagnostic procedures for staging, initial prostate specific antigen (iPSA), and Gleason Score sum of biopsy. For each clinical case, radiation oncologists were asked to: (a) give indication to pretreatment procedures for staging; (b) give indication to treatment; (c) define specifically, where indicated, total dose, type of fractionation, volumes of treatment, type of technique, type of image-guided setup control; (d) indicate if HT should be prescribed; (e) define criteria that particularly influenced prescription. A descriptive statistical analysis was performed., Results: Three hundred questionnaires were given to radiation oncologists attending the congress, 128 questionnaires were completed and considered for this analysis (41%). Some important differences were shown in prescribing and delivering RT, particularly with regards to treatment volumes and fractionation., Conclusions: Despite the results of clinical trials, several differences still exist among Italian radiation oncologists in the treatment of prostate cancer patients. These patients probably deserve a more uniform approach, based on upto-date, detailed, and evidence-based recommendations.

Aim: The purpose of this study was to evaluate the potential usefulness of [18F]-Choline PET/CT in the restaging of prostate cancer patients, who presented a rising PSA., Materials and Methods: We evaluated 170 prostate cancer patients, previously radically treated, that were referred for restaging with [18F]-Choline PET/CT., Results: A total of 129 patients (median PSA 4.29 ng/ml at relapse) showed one or more areas of high uptake on PET/CT scan, while 41 patients with a median PSA of 1.07 ng/ml at relapse showed negative PET/CT scans. No false negative was found, while 31 patients were identified as false positive. Specificity of Choline PET/CT in our series was 56.9 %, while sensibility was 100 %. At the time of restaging, a PSA value superior or equal to 1 ng/ml was found to be a statistically significant predictive factor of PET positivity, either at the univariate (p < 0.0001) and at the multivariate analysis (p < 0.0001)., Conclusions: Based on our findings, [18F]-Choline PET/CT is confirmed as a useful diagnostic tool to detect early recurrence, in patients with increasing PSA after primary treatment. However, in case of a mild increase in PSA, positive results must be validated with other techniques, as specificity and positive predictive value of [18F]-Choline PET/CT decrease with the lower values of PSA.

Aim: In men with adverse pathology after radical prostatectomy, the most appropriate timing to administer radiotherapy (RT) remains a topic of debate. We analyzed in terms of efficacy, prognostic factors and toxicity the two therapeutic strategies: immediate postoperative radiotherapy (PORT) and salvage radiotherapy (SART)., Materials and Methods: Between January 1995 and November 2010, 307 patients underwent adjuvant or salvage radiotherapy, after prostatectomy., Results: In the PORT group, 42 patients (20.7 %) had biochemical failure, with a median time to biochemical failure of 1.8 years; two parameters (age at diagnosis and PSA pre-RT) resulted to be significant at the survival analysis for overall survival (p = 0.003 and p = 0.046, respectively). In the SART group, 33 patients (31.7 %) had biochemical relapse; sixteen patients died of prostate cancer; postoperative hormones therapy, conformal radiotherapy and level of PSA pre-RT >1.0 ng/ml resulted to be significant at the survival analysis, p = 0.009, p = 0.039 and p = 0.002, respectively., Conclusion: Our study is limited by its retrospective and nonrandomized design. As such, decisions to treat with adjuvant or salvage radiotherapy and the time to initiate therapy were based on patient preference and physician counseling. Our recommendation is to suggest adjuvant radiotherapy for all patients with adverse prognostic factors and to reserve salvage radiotherapy for low-risk patients, when the biochemical recurrence occurs.

Introduction: The usual treatment options for clinically localized prostate cancer carry a significant risk of lasting side effects, including urinary, bowel, and sexual dysfunction, that can alter overall the patient's quality of life. The aim of this research is to evaluate the impact of treatment timing (age at time of treatment, follow-up duration, age at time of follow-up), pretreatment tumor characteristics (clinical stage, Gleason score, PSA), and posttreatment outcomes (hormonal status, biochemical recurrence), on health-related quality of life (HRQOL) among men who had undergone radical treatment for prostate cancer., Materials and Methods: 595 patients with prostate cancer who had undergone either radical prostatectomy or external beam radiation as primary therapy between 1988 and 2000 were selected for this retrospective, cross-sectional study. The enrolled subjects were asked to complete the Italian validated version of University of California-Los Angeles Prostate Cancer Index. Clinical parameters, hormone therapy status and posttreatment outcomes were considered to perform uni- and multivariate analyses., Results: Both uni- and multivariate analyses demonstrated that timing of radical treatment is a critical predictive factor for sexual activity. Pretreatment tumor characteristics had a significant impact on urinary function, urinary bother and sexual function. Hormone treatment exclusively influenced sexual function and sexual bother, while biochemical recurrence can also worsen urinary symptoms and urinary bother., Conclusion: Our findings suggest that treatment timing, pretreatment tumor characteristics and posttreatment outcomes may have an impact on HRQOL in patients who have undergone radical treatment for prostate cancer: all these items should be considered in order to achieve an accurate interpretation of prostate cancer treatment outcomes., (2008 S. Karger AG, Basel)

Aims and Background: The development and use of new radiotherapy techniques, especially 3D conformal radiotherapy or intensity-modulated radiotherapy, has allowed the safe application of high doses of external beam radiotherapy without increasing toxicity. The aim of this analysis was to describe the acute and when possible late toxicity and the feasibility on using intensity-modulated radiotherapy into our routine work., Patients and Methods: From June 2003 to December 2004, 60 patients with prostate cancer underwent high dose (80 Gy) radiotherapy treatment with intensity-modulated radiotherapy at the University of Florence. In the current analysis, we included patients without clinical or radiographic evidence of distant disease at the time of the first evaluation in the radiotherapy unit., Results: Intensity-modulated radiotherapy treatments were delivered successfully without any interruption or technical problem. High-dose intensity-modulated radiotherapy was well tolerated acutely. Four patients (10%) developed grade 1 late rectal toxicity after completion of intensity-modulated radiotherapy and 8 patients (20%) developed grade 1 late urinary symptoms., Conclusions: Intensity-modulated radiotherapy is the approach of choice for high-dose radiotherapy delivery. No patient had severe toxicity (grade 3) despite the high dose delivered. From a cost-benefit point of view, our experience shows that delivery of intensity-modulated radiotherapy requires only minor corrections to the ordinary activity schedule.

Purpose: Prostate cancer patients in Italy are offered the choice of the full spectrum of possible treatment options for their disease, but the diffusion of the more recent technological refinements among the Radiation Oncology centers is not homogeneous and there is a need to establish a reference "historical" data source. This retrospective study describes the changing patterns in prostate cancer patient practice and the therapeutic results obtained in nine Radiation Oncology centers of Northern and Central Italy (five in Northern Italy and four in Central Italy)., Methods and Materials: A total of 1759 prostate cancer patients, radically treated in the nine radiotherapy (RT) centers between 1980 and 1998, made up the study population. Data collected for each patient included clinical, pathologic, therapeutic features, and toxicity. The overall survival, disease-specific survival (DSS), and clinical relapse-free survival (RFS) were calculated for the whole series and for the subsets of patients defined by different clinical, pathologic, and therapeutic features, according to three accrual periods (A, 1980-1990; B, 1991-1994; and C, 1995-1998). Univariate and multivariate analyses were performed to identify prognostic factors related to survival and late adverse effects (cystitis and proctitis) probability., Results: Patient accrual increased markedly during the 2 decades considered, and the percentage of cases with Stage C or D disease dropped from 49% (period A) to 43% (period B) to 37% (period C) (p < 0.0001, chi-square). The baseline prostate-specific antigen value was available for 10%, 76%, and 95% of the cases treated in the three different periods. The major changes in the therapeutic options were an increase in dose to the prostate (>66 Gy in 44%, 84%, and 93% of the patients treated in period A, B, and C, respectively); a reduction in treated volumes, including pelvic lymphatic drainage (56-39% before 1995, 22% thereafter); and an increase in cases treated in association with hormonal therapy (50% before 1991, 80% thereafter). Lower energy (<10 MV) photon beams were progressively abandoned (12% before 1990 vs. 6-7% thereafter), along with an increase in the use of blocks (60% in the last 4 years of the study vs. about 30-40% before 1995) and "conformal" RT (applied in 41% of cases treated after 1994). The actuarial RFS, DSS, and overall survival rate at 5 years was, respectively, 60% +/- 2%, 75% +/- 2%, 66% +/- 2% for period A; 74% +/- 2%, 90% +/- 1%, 83% +/- 2%, for period B; and 67% +/- 5%, 90% +/- 2%, 79% +/- 5% for period C. The actuarial overall survival, DSS, and RFS rate for the whole series of 1759 patients was 77% +/- 1%, 86% +/- 1%, and 68% +/- 1% at 5 years, respectively. Multivariate analysis showed that only American Urologic Association stage, grade, dose to the prostate, accrual period, association with hormonal treatment after (or both after and before) RT (only in terms of DSS and RFS), and baseline prostate-specific antigen value (only for RFS) retained prognostic significance in the final Cox model., Conclusion: The increase in the accrual of prostate cancer patients radically treated with RT has been accompanied by considerable changes in the clinical features at presentation, as well as in the staging and treatment procedures. Patients treated more recently had better survival results. An earlier stage and more favorable grade were linked with better overall, DSS, and RFS at multivariate analysis. Lower prostate-specific antigen baseline values were also related to better RFS. Better results were obtained with higher radiation doses, and the dose to tumor seemed the most important treatment-related prognostic factor. The toxicity (cystitis and proctitis, every Radiation Therapy Oncology Group grade) was substantially the same in the different accrual periods, but larger treated volumes and higher doses appeared to increase the incidence of late effects.