Publications by authors named "Alberto Bossi"

98 Publications

Lack of consensus identifies important areas for future clinical research: Advanced Prostate Cancer Consensus Conference (APCCC) 2019 findings.

Eur J Cancer 2021 Nov 26. Epub 2021 Nov 26.

Oncology Institute of Southern Switzerland, EOC, Bellinzona, Switzerland; University of Bern, Bern, Switzerland; Università della Svizzera Italiana, Lugano, Switzerland; Division of Cancer Science, University of Manchester, Manchester, UK. Electronic address:

Background: Innovations in treatments, imaging and molecular characterisation have improved outcomes for people with advanced prostate cancer; however, many aspects of clinical management are devoid of high-level evidence. At the Advanced Prostate Cancer Consensus Conference (APCCC) 2019, many of these topics were addressed, and consensus was not always reached. The results from clinical trials will most reliably plus the gaps.

Methods: An invited panel of 57 experts voted on 123 multiple-choice questions on clinical management at APCCC 2019. No consensus was reached on 88 (71.5%) questions defined as <75% of panellists voting for the same answer option. We reviewed clinicaltrials.gov to identify relevant ongoing phase III trials in these areas of non-consensus.

Results: A number of ongoing phase III trials were identified that are relevant to these non-consensus issues. However, many non-consensus issues appear not to be addressed by current clinical trials. Of note, no phase III but only phase II trials were identified, investigating side effects of hormonal treatments and their management.

Conclusions: Lack of consensus almost invariable indicates gaps in existing evidence. The high percentage of questions lacking consensus at APCCC 2019 highlights the complexity of advanced prostate cancer care and the need for robust, clinically relevant trials that can fill current gaps with high-level evidence. Our review of these areas of non-consensus and ongoing trials provides a useful summary, indicating areas in which future consensus may soon be reached. This review may facilitate academic investigators to identify and prioritise topics for future research.
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http://dx.doi.org/10.1016/j.ejca.2021.09.036DOI Listing
November 2021

Current and Emerging Therapies for Metastatic Castration-Resistant Prostate Cancer (mCRPC).

Biomedicines 2021 Sep 17;9(9). Epub 2021 Sep 17.

Department of Radiation Oncology, Clinical Department, Faculty of Biomedicine, Hospital Universitario Quirónsalud Madrid, Hospital La Luz, Universidad Europea, 28223 Madrid, Spain.

Metastatic castration-resistant prostate cancer (mCRPC) encompasses a heterogeneous wide range of molecular tumor behavior and a high risk of progression. Early detection and treatment are therefore crucial in these patients. Treatment has improved drastically in recent years and many novel therapeutic agents are currently under investigation. However, due to the rapidly changing therapeutic landscape in mCRPC, it is difficult for clinicians to keep up to date with the latest innovations in this area. In the present narrative review, we discuss the current and emerging therapies for mCRPC as well as the clinical and molecular factors that can help predict which patients are most likely to benefit from these novel agents.
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http://dx.doi.org/10.3390/biomedicines9091247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468423PMC
September 2021

Driving Organic Nanocrystals Dissolution Through Electrochemistry.

ChemistryOpen 2021 08;10(8):748-755

Department of Physics, Politecnico di Milano, p.za Leonardo da Vinci 32, Milano, 20133 Milano, Italy.

We have recently discussed how organic nanocrystal dissolution appears in different morphologies and the role of the solution pH in the crystal detriment process. We also highlighted the role of the local molecular chemistry in porphyrin nanocrystals having comparable structures: in water-based acid solutions, protonation of free-base porphyrin molecules is the driving force for crystal dissolution, whereas metal (Zn ) porphyrin nanocrystals remain unperturbed. However, all porphyrin types, having an electron rich π-structure, can be electrochemically oxidized. In this scenario, a key question is: does electrochemistry represent a viable strategy to drive the dissolution of both free-base and metal porphyrin nanocrystals? In this work, by exploiting electrochemical atomic force microscopy (EC-AFM), we monitor in situ and in real time the dissolution of both free-base and metal porphyrin nanocrystals, as soon as molecules reach the oxidation potential, showing different regimes according to the applied EC potential.
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http://dx.doi.org/10.1002/open.202100076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340066PMC
August 2021

Elective nodal radiotherapy in prostate cancer.

Lancet Oncol 2021 08;22(8):e348-e357

Department of Radiation Oncology, Gustave Roussy Institute, Paris, France.

In patients with prostate cancer who have a high risk of pelvic nodal disease, the use of elective whole pelvis radiotherapy is still controversial. Two large, randomised, controlled trials (RTOG 9413 and GETUG-01) did not show a benefit of elective whole pelvis radiotherapy over prostate-only radiotherapy. In 2020, the POP-RT trial established the role of elective whole pelvis radiotherapy in patients who have more than a 35% risk of lymph node invasion (known as the Roach formula). POP-RT stressed the importance of patient selection. In patients with cN1 (clinically node positive) disease or pN1 (pathologically node positive) disease, the addition of whole pelvis radiotherapy to androgen deprivation therapy significantly improved survival compared with androgen deprivation therapy alone, as shown in large, retrospective studies. This patient population might increase in the future because use of the more sensitive prostate-specific membrane antigen PET-CT will become the standard staging procedure. Additionally, the SPORTT trial suggested a benefit of whole pelvis radiotherapy in biochemical recurrence-free survival in the salvage setting. A correct definition of the upper field border, which should include the bifurcation of the abdominal aorta, is key in the use of pelvic radiotherapy. As a result of using modern radiotherapy technology, severe late urinary and intestinal toxic effects are rare and do not seem to increase compared with prostate-only radiotherapy.
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http://dx.doi.org/10.1016/S1470-2045(21)00242-4DOI Listing
August 2021

Salvage stereotactic body radiotherapy (SBRT) for intraprostatic relapse after prostate cancer radiotherapy: An ESTRO ACROP Delphi consensus.

Cancer Treat Rev 2021 Jul 20;98:102206. Epub 2021 Apr 20.

Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

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.
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http://dx.doi.org/10.1016/j.ctrv.2021.102206DOI Listing
July 2021

Contemporary Imaging Technologies for Men with Rising Prostate-specific Antigen After Radical Prostatectomy and Before Early Salvage Irradiation: Where Do We Stand?

Eur Urol Oncol 2021 Jun 24;4(3):356-357. Epub 2021 Mar 24.

Department of Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; University of Bologna, Bologna, Italy.

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http://dx.doi.org/10.1016/j.euo.2021.03.003DOI Listing
June 2021

Systematic Screening of COVID-19 Disease Based on Chest CT and RT-PCR for Cancer Patients Undergoing Radiation Therapy in a Coronavirus French Hotspot.

Int J Radiat Oncol Biol Phys 2021 07 17;110(4):947-956. Epub 2021 Feb 17.

Department of Radiation Oncology, Gustave Roussy, Paris-Saclay University, Villejuif, France; Radiothérapie Moléculaire et Innovation Thérapeutique, Paris-Saclay University, Gustave Roussy, Villejuif, France. Electronic address:

Purpose: Patients with cancer are presumed to be more vulnerable to COVID-19. We evaluated a screening strategy combining chest computed tomography (CT) and reverse-transcription polymerase chain reaction (RT-PCR) for patients treated with radiation therapy at our cancer center located in a COVID-19 French hotspot during the first wave of the pandemic.

Methods And Materials: Chest CT images were proposed during radiation therapy CT simulation. Images were reviewed by an expert radiologist according to the COVID-19 Reporting and Data System classification. Nasal swabs with RT-PCR assay were initially proposed in cases of suspicious imaging or clinical context and were eventually integrated into the systematic screening. A dedicated radiation therapy workflow was proposed for COVID-19 patients to limit the risk of contamination.

Results: From March 18, 2020 to May 1, 2020, 480 patients were screened by chest CT, and 313 patients had both chest CT and RT-PCR (65%). The cumulative incidence of COVID-19 was 5.4% (95% confidence interval [CI], 3.6-7.8; 26 of 480 patients). Diagnosis of COVID-19 was made before radiation therapy for 22 patients (84.6%) and during RT for 4 patients (15.3%). Chest CT directly aided the diagnosis of 7 cases in which the initial RT-PCR was negative or not feasible, out of a total of 480 patients (1.5%) and 517 chest CT acquisitions. Four patients with COVID-19 at the time of the chest CT screening had a false negative CT. Sensitivity and specificity of chest CT screening in patients with both RT-PCR and chest CT testing were estimated at 0.82 (95% CI, 0.60-0.95) and 0.98 (95% CI, 0.96-0.99), respectively. Adaptation of the radiation therapy treatment was made for all patients, with 7 postponed treatments (median: 5 days; interquartile range, 1.5-14.8).

Conclusions: The benefit of systematic use of chest CT screening during CT simulation for patients undergoing radiation therapy during the COVID-19 pandemic seemed limited.
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http://dx.doi.org/10.1016/j.ijrobp.2021.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887448PMC
July 2021

Nucleobase morpholino β amino acids as molecular chimeras for the preparation of photoluminescent materials from ribonucleosides.

Sci Rep 2020 11 9;10(1):19331. Epub 2020 Nov 9.

DISFARM-Dipartimento Di Scienze Farmaceutiche, Sezione Chimica Generale E Organica "A. Marchesini", Università Degli Studi Di Milano, Via Venezian 21, 20133, Milan, Italy.

Bioinspired smart materials represent a tremendously growing research field and the obtainment of new building blocks is at the molecular basis of this technology progress. In this work, colloidal materials have been prepared in few steps starting from ribonucleosides. Nucleobase morpholino β-amino acids are the chimera key intermediates allowing Phe-Phe dipeptides' functionalization with adenine and thymine. The obtained compounds self-aggregate showing enhanced photoluminescent features, such as deep blue fluorescence and phosphorescence emissions.
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http://dx.doi.org/10.1038/s41598-020-76297-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652887PMC
November 2020

Final Analysis of the Ipilimumab Versus Placebo Following Radiotherapy Phase III Trial in Postdocetaxel Metastatic Castration-resistant Prostate Cancer Identifies an Excess of Long-term Survivors.

Eur Urol 2020 12 15;78(6):822-830. Epub 2020 Aug 15.

The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.

Background: The phase 3 trial CA184-043 evaluated radiotherapy to bone metastases followed by Ipilimumab or placebo in men with metastatic castrate-resistant prostate cancer (mCRPC) who had received docetaxel previously. In a prior analysis, the trial's primary endpoint (overall survival [OS]) was not improved significantly.

Objective: To report the final analysis of OS.

Design, Setting, And Participants: A total of 799 patients were randomized to receive a single dose of radiotherapy to one or more bone metastases followed by either Ipilimumab (n = 399) or placebo (n = 400).

Outcome Measurements And Statistical Analysis: OS was analyzed in the intention-to-treat population. Prespecified and exploratory subset analyses based on Kaplan-Meier/Cox methodology were performed.

Results And Limitations: During an additional follow-up of approximately 2.4 yr since the primary analysis, 721/799 patients have died. Survival analysis showed crossing of the curves at 7-8 mo, followed by persistent separation of the curves beyond that point, favoring the ipilimumab arm. Given the lack of proportional hazards, a piecewise hazard model showed that the hazard ratio (HR) changed over time: the HR was 1.49 (95% confidence interval 1.12, 1.99) for 0-5 mo, 0.66 (0.51, 0.86) for 5-12 mo, and 0.66 (0.52, 0.84) beyond 12 mo. OS rates were higher in the ipilimumab versus placebo arms at 2 yr (25.2% vs 16.6%), 3 yr (15.3% vs 7.9%), 4 yr (10.1% vs 3.3%), and 5 yr (7.9% vs. 2.7%). Disease progression was the most frequent cause of death in both arms. In seven patients (1.8%) in the ipilimumab arm and one (0.3%) in the placebo arm, the primary cause of death was reported as study drug toxicity. No long-term safety signals were identified.

Conclusions: In this preplanned long-term analysis, OS favored ipilimumab plus radiotherapy versus placebo plus radiotherapy for patients with postdocetaxel mCRPC. OS rates at 3, 4, and 5 yr were approximately two to three times higher in the ipilimumab arm.

Patient Summary: After longer follow-up, survival favored the group of men who received ipilimumab, with overall survival rates being two to three times higher at 3 yr and beyond.
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http://dx.doi.org/10.1016/j.eururo.2020.07.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428575PMC
December 2020

Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer.

N Engl J Med 2020 06 29;382(23):2187-2196. Epub 2020 May 29.

From the Carolina Urologic Research Center, Myrtle Beach, SC (N.D.S.); the University of Montreal Hospital Center, Montreal (F.S.); the Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City (M.S.C.); the Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC (D.J.G.); Urology San Antonio, San Antonio, TX (D.R.S.); Chesapeake Urology, Towson, MD (R.T.); the Department of Strategic Investigation on Comprehensive Cancer Network, Interfaculty Initiative in Information Studies-Graduate School of Interdisciplinary Information Studies, University of Tokyo, Tokyo (H.A.); the Department of Radiation Oncology, Gustave Roussy Cancer Institute, Villejuif, France (A.B.); Myovant Sciences, Brisbane, CA (D.F.V., B.S., X.F., V.K., J.W.); and Service d'Urologie, Cliniques Universitaires Saint Luc, Brussels (B.T.).

Background: Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known.

Methods: In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients.

Results: A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88).

Conclusions: In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).
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http://dx.doi.org/10.1056/NEJMoa2004325DOI Listing
June 2020

Risks from Deferring Treatment for Genitourinary Cancers: A Collaborative Review to Aid Triage and Management During the COVID-19 Pandemic.

Eur Urol 2020 Jul 3;78(1):29-42. Epub 2020 May 3.

Department of Surgery, Division of Urology, Augusta University-Medical College of Georgia, Augusta, GA, USA; Georgia Cancer Center, Augusta, GA, USA. Electronic address:

Context: The coronavirus disease 2019 (COVID-19) pandemic is leading to delays in the treatment of many urologic cancers.

Objective: To provide a contemporary picture of the risks from delayed treatment for urologic cancers to assist with triage.

Evidence Acquisition: A collaborative review using literature published as of April 2, 2020.

Evidence Synthesis: Patients with low-grade non-muscle-invasive bladder cancer are unlikely to suffer from a 3-6-month delay. Patients with muscle-invasive bladder cancer are at risk of disease progression, with radical cystectomy delays beyond 12 wk from diagnosis or completion of neoadjuvant chemotherapy. Prioritization of these patients for surgery or management with radiochemotherapy is encouraged. Active surveillance should be used for low-risk prostate cancer (PCa). Treatment of most patients with intermediate- and high-risk PCa can be deferred 3-6 mo without change in outcomes. The same may be true for cancers with the highest risk of progression. With radiotherapy, neoadjuvant androgen deprivation therapy (ADT) is the standard of care. For surgery, although the added value of neoadjuvant ADT is questionable, it may be considered if a patient is interested in such an approach. Intervention may be safely deferred for T1/T2 renal masses, while locally advanced renal tumors (≥T3) should be treated expeditiously. Patients with metastatic renal cancer may consider vascular endothelial growth factor targeted therapy over immunotherapy. Risks for delay in the treatment of upper tract urothelial cancer depend on grade and stage. For patients with high-grade disease, delays of 12 wk in nephroureterectomy are not associated with adverse survival outcomes. Expert guidance recommends expedient local treatment of testis cancer. In penile cancer, adverse outcomes have been observed with delays of ≥3 mo before inguinal lymphadenectomy. Limitations include a paucity of data and methodologic variations for many cancers.

Conclusions: Patients and clinicians should consider the oncologic risk of delayed cancer intervention versus the risks of COVID-19 to the patient, treating health care professionals, and the health care system.

Patient Summary: The coronavirus disease 2019 pandemic has led to delays in the treatment of patients with urologic malignancies. Based on a review of the literature, patients with high-grade urothelial carcinoma, advanced kidney cancer, testicular cancer, and penile cancer should be prioritized for treatment during these challenging times.
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http://dx.doi.org/10.1016/j.eururo.2020.04.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196384PMC
July 2020

Long-term Castration-related Outcomes in Patients With High-risk Localized Prostate Cancer Treated With Androgen Deprivation Therapy With or Without Docetaxel and Estramustine in the UNICANCER GETUG-12 Trial.

Clin Genitourin Cancer 2020 12 7;18(6):444-451. Epub 2020 Apr 7.

Department of Cancer Medicine, Institut Gustave Roussy, Villejuif, France. Electronic address:

Introduction: Neoadjuvant chemotherapy with docetaxel and estramustine (DE) significantly improved relapse-free survival in patients with high-risk localized prostate cancer treated with androgen deprivation therapy (ADT) for 3 years and a local treatment in the GETUG-12 phase III trial. We sought to explore whether the addition of DE impacts long-term treatment-related side effects.

Patients And Methods: Patients randomized within the UNICANCER GETUG-12 trial at Gustave Roussy who were alive when ADT was discontinued were followed-up prospectively. Serum testosterone levels and clinical data regarding body weight, libido, erection, and cardio-vascular events were collected.

Results: Seventy-eight patients were included: 36 patients had been treated with ADT plus a local treatment and 42 with ADT+DE plus a local treatment. With a median follow-up of 5.9 years after ADT discontinuation, serum testosterone levels returned to normal values (> 200 ng/mL) for 57 (78%) of 72 evaluable patients, and 29 (43%) of 68 evaluable patients reported erections allowing intercourse without medical assistance. No impact of DE on testosterone level recovery, libido, quality of erections, and changes in body weight after ADT discontinuation was detected. The incidence of cardiovascular events was low and similar in both treatment arms.

Conclusion: Treatment with DE was not associated with excess long-term castration-related toxicity in men with high-risk localized prostate cancer. The relapse-free survival improvement seen with DE in GETUG-12 is likely not related to differed testosterone recovery.
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http://dx.doi.org/10.1016/j.clgc.2020.03.017DOI Listing
December 2020

The Quantum Efficiency Roll-Off Effect in Near-Infrared Organic Electroluminescent Devices with Iridium Complexes Emitters.

Materials (Basel) 2020 Apr 15;13(8). Epub 2020 Apr 15.

Department of Physics of Electronic Phenomena, Faculty of Applied Physics and Mathematics, Gdańsk University of Technology, Narutowicza 11/12, 80-233 Gdańsk, Poland.

The electroluminescence quantum efficiency roll-off in iridium(III)-based complexes, namely Ir(iqbt)(dpm) and Ir(iqbt) (iqbt = 1 (benzo[b]thiophen-2-yl)-isoquinolinate, dpm = 2,2,6,6-tetramethyl-3,5-heptanedionate) utilized as near-infrared emitters in organic light emitting diodes with remarkable external quantum efficiencies, up to circa 3%, 1.5% and 1%, are measured and analyzed. With a 5-6 weight% of emitters embedded in a host matrix, the double-layer solution-processed structure as well as analogous three-layer one extended by a hole-conducting film are investigated. The triplet-polaron, the Onsager electron-hole pair dissociation and the triplet-triplet annihilation approaches were used to reproduce the experimental data. The mutual annihilation of triplets in iridium emitters was identified as prevailingly controlling the moderate roll-off, with the interaction between those of iridium emitters and host matrixes found as being less probable. Following the fitting procedure, the relevant rate constant was estimated to be ( 0.5 - 12 ) × 10 - 12 cm/s, values considered to be rather too high for disordered organic systems, which was assigned to the simplicity of the applied model. A coexistence of some other mechanisms is therefore inferred, ones, however, with a less significant contribution to the overall emission quenching.
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http://dx.doi.org/10.3390/ma13081855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215655PMC
April 2020

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019.

Eur Urol 2020 04 27;77(4):508-547. Epub 2020 Jan 27.

Division of Medical Oncology, National Cancer Centre, Singapore.

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.

Objective: To present the results from the APCCC 2019.

Design, Setting, And Participants: Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.

Outcome Measurements And Statistical Analysis: The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.

Results And Limitations: Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.

Conclusions: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.

Patient Summary: The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.
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http://dx.doi.org/10.1016/j.eururo.2020.01.012DOI Listing
April 2020

Ab Initio Many-Body Perturbation Theory Calculations of the Electronic and Optical Properties of Cyclometalated Ir(III) Complexes.

J Chem Theory Comput 2020 Feb 6;16(2):1188-1199. Epub 2020 Jan 6.

Consiglio Nazionale delle Ricerche , Istituto di Scienze e Tecnologie Chimiche (CNR-SCITEC) , 20133 Milano , Italy.

Cyclometalated Ir(III) compounds are the preferred choice as organic emitters in organic light-emitting diodes. In practice, the presence of the transition metal surrounded by carefully designed ligands allows fine-tuning of the emission frequency as well as good efficiency of the device. To support the development of new compounds, experimental measurements are generally compared with absorption and emission spectra obtained from ab initio calculations. The standard approach for these calculations is time-dependent density functional theory (TDDFT) with a hybrid exchange-correlation functional like B3LYP. Because of the size of these compounds, the application of more complex quantum chemistry approaches can be challenging. In this work, we used many-body perturbation theory approaches, in particular the GW approximation with the Bethe-Salpeter equation (BSE) implemented in Gaussian basis sets, to calculate the quasiparticle properties and the absorption spectra of six cyclometalated Ir(III) complexes, going beyond TDDFT. In the presented results, we compared standard TDDFT simulations with BSE calculations performed on top of perturbative GW and accounting for eigenvalue self-consistency. Moreover, in order to investigate in detail the effect of the DFT starting point, we concentrated on Ir(ppy) and performed GW-BSE simulations starting from different DFT exchange-correlation potentials.
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http://dx.doi.org/10.1021/acs.jctc.9b00763DOI Listing
February 2020

Defining the Most Informative Intermediate Clinical Endpoints for Patients Treated with Salvage Radiotherapy for Prostate-specific Antigen Rise After Radical Prostatectomy.

Eur Urol Oncol 2021 04 4;4(2):301-304. Epub 2019 Dec 4.

Division of Oncology, Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Intermediate clinical endpoints (ICEs) might aid in trial design and potentially expedite study results. However, little is known about the most informative ICE for patients receiving salvage radiation therapy (sRT) after radical prostatectomy. To investigate the most informative ICE for patients receiving sRT, we used a multi-institutional database encompassing patients treated at eight tertiary centers. Overall, 1301 men with node-negative disease who had not received any form of androgen deprivation therapy were identified. Associations of biochemical (BCR) and clinical recurrence (CR) within 1, 3, 5, and 7yr after surgery with the risk of overall mortality were evaluated using multivariable Cox regression analyses fitted at the landmark points of 1, 3, 5, and 7yr after sRT. The discriminative ability of each model for predicting overall survival (OS) was assessed using Harrell's c index. Median follow-up for survivors was 5.6yr (interquartile range 2.0-8.8). On multivariable analysis, progression to CR within 3yr from sRT (hazard ratio 4.19, 95% confidence interval 1.44-11.2; p= 0.008) was the most informative ICE for predicting OS (c index 0.78) compared to CR within 1, 5, and 7yr (c index 0.72, 0.75, and 0.71). In conclusion, progression to CR within 3yr after sRT, irrespective of the time of surgery, was the most informative ICE for prediction of OS. Our study is hypothesis-generating. If these results are confirmed in future prospective studies and surrogacy is met, this information could be applied for study design and could potentially expedite earlier release of results from ongoing randomized controlled trials. PATIENT SUMMARY: Clinical recurrence of prostate cancer within 3yr after salvage radiation therapy, irrespective of the time of radical prostatectomy, represents the most informative intermediate clinical endpoint for the prediction of overall survival. This information could be applied in the design of future studies and could potentially expedite earlier release of results from ongoing randomized controlled trials.
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http://dx.doi.org/10.1016/j.euo.2019.11.003DOI Listing
April 2021

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort: Under the Auspices of the EAU-ESMO Guidelines Committees.

Eur Urol 2020 02 19;77(2):223-250. Epub 2019 Nov 19.

Department of Biomedical Sciences, Humanitas University, Milan, Italy; Humanitas Research Hospital, Milan, Italy.

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.

Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.

Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.

Setting: Online Delphi survey and consensus conference.

Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.

Outcome Measurements And Statistical Analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).

Results And Limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.

Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.

Patient Summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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http://dx.doi.org/10.1016/j.eururo.2019.09.035DOI Listing
February 2020

EAU-EANM-ESTRO-ESUR-SIOG Prostate Cancer Guideline Panel Consensus Statements for Deferred Treatment with Curative Intent for Localised Prostate Cancer from an International Collaborative Study (DETECTIVE Study).

Eur Urol 2019 Dec 3;76(6):790-813. Epub 2019 Oct 3.

Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Background: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised.

Objective: To develop consensus statements for all domains of DAT.

Design, Setting, And Participants: A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains; (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients; and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed.

Results And Limitations: A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%); the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion.

Conclusions: Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials.

Patient Summary: We undertook a project aimed at standardising the elements of practice in active surveillance programmes for early localised prostate cancer because currently there is great variation and uncertainty regarding how best to conduct them. The project involved large numbers of healthcare practitioners and patients using a survey and face-to-face meeting, in order to achieve agreement (ie, consensus) regarding best practice, which will provide guidance to clinicians and researchers.
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http://dx.doi.org/10.1016/j.eururo.2019.09.020DOI Listing
December 2019

Regression Discontinuity Analysis of Salvage Radiotherapy in Prostate Cancer.

Eur Urol Oncol 2021 Oct 6;4(5):817-820. Epub 2019 Sep 6.

Center for Outcomes Research, Analytics and Evaluation, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA. Electronic address:

There is a lack of randomized evidence comparing early (eSRT) to late (lSRT) salvage radiotherapy (SRT) after radical prostatectomy (RP) for prostate cancer (PCa). Moreover, the existing evidence is often affected by lead-time bias. We sought to address this gap in a cohort of 1458 PCa patients undergoing SRT for biochemical recurrence (BCR) after RP in two tertiary care centers between 1992 and 2013. Using a quasi-randomized study design known as regression discontinuity (RD) and adjusting for lead-time bias, we compared metastasis-free survival (MFS) at 5 and 10 years after surgery between eSRT (prostate-specific antigen [PSA] <0.5 ng/ml) and lSRT (PSA ≥ 0.5 ng/ml). Overall, 1049 patients (71.9%) underwent eSRT and 409 (28.1%) lSRT at a mean follow-up of 84 mo (interquartile range (IQR) 52-120.4). The MFS rate decreased nonsignificantly at the proposed cutoff by 0.04 (95% confidence interval [CI]: -0.06 to 0.19) at 5 years and by 0.07 (95% CI: - 0.12 to 0.32) at 10 years. Cox regression analysis revealed a hazard ratio for the cutoff examined of 1.3 (95% CI: 0.8-2.4; p = 0.2). In conclusion, in a quasirandomized study design accounting for lead-time bias, eSRT (PSA < 0.5 ng/ml) did not improve MFS. Our results underline the need for level-one evidence to compare eSRT and lSRT. PATIENT SUMMARY: We compared early versus late salvage radiotherapy (SRT) for biochemical recurrence after radical prostatectomy by simulating a randomized trial. We found that early SRT (initiated at prostate-specific antigen <0.5 ng/ml) compared to late SRT did not improve metastasis-free survival.
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http://dx.doi.org/10.1016/j.euo.2019.08.005DOI Listing
October 2021

Salvage Local Treatments After Focal Therapy for Prostate Cancer.

Eur Urol Oncol 2019 09 15;2(5):526-538. Epub 2019 Apr 15.

Department of Urology, MD Anderson Cancer Center, TX, USA.

Context: Whether focal therapy (FT) for prostate cancer (PC) jeopardizes outcomes from salvage treatments is a matter of debate still to be resolved.

Objective: To review the literature on oncological and functional outcomes and complications for available treatment options for recurrent or residual PC after primary FT.

Evidence Acquisition: We performed a nonsystematic search of PubMed for articles assessing relevant outcomes for salvage local treatment after FT failure using a manual search. When no evidence could be extracted for the FT domain, records dealing with recurrence after whole-gland ablation were considered.

Evidence Synthesis: Four retrospective series assessed salvage treatments after FT failure evaluating cases of radical prostatectomy (RP) and repeat ablation (sample size from 12 to 22 patients). The quality of the studies was low, with a high risk of bias. Other options are radiation therapy (RT) and whole-gland or focal repeat ablations, although these have only been described after whole-gland ablation. With some exceptions, including sexual function for RP, overall complications and oncological and functional outcomes do seem to be acceptable and are not much worse than those in the primary setting. Important limitations include the low level of the evidence and the absence of standardized criteria for FT, salvage treatment, and FT failure.

Conclusions: Current evidence shows acceptable outcomes for post-FT salvage options, although this is based on retrospective data. While it seems that FT has a minimal impact on salvage treatment results, prospective controlled studies are needed to confirm these preliminary data.

Patient Summary: We performed a literature search to determine the treatment options available for prostate cancer after failure of focal therapy and their outcomes. Options include radical prostatectomy, repeat whole-gland ablation, focal ablation, and radiotherapy. Overall cancer control, impacts on urinary and sexual function, and complications seem slightly worse but not markedly different compared to primary treatments, but high-quality studies are awaited to confirm these findings.
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http://dx.doi.org/10.1016/j.euo.2019.03.008DOI Listing
September 2019

Nonsurgical Salvage Local Therapies for Radiorecurrent Prostate Cancer: A Systematic Review and Meta-analysis.

Eur Urol Oncol 2020 04 24;3(2):183-197. Epub 2019 Jan 24.

Department of Radiation Oncology, A.O.U. Careggi, University of Florence, Florence, Italy.

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=63.4%) and the highest was among patients treated with HIFU (28%, 95% CI 19-38%; I=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.
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http://dx.doi.org/10.1016/j.euo.2018.12.011DOI Listing
April 2020

Brachytherapy: An overview for clinicians.

CA Cancer J Clin 2019 09 30;69(5):386-401. Epub 2019 Jul 30.

Department of Radiation Oncology, Gustave Roussy Comprehensive Cancer Center, Villejuif, France.

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.
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http://dx.doi.org/10.3322/caac.21578DOI Listing
September 2019

Uniaxial Alignment of a Monolayer of Flat-on Free-Base Porphyrins on an Exfoliable Insulating Substrate.

Nano Lett 2019 08 15;19(8):5537-5543. Epub 2019 Jul 15.

Department of Physics , Politecnico di Milano , p.za Leonardo da Vinci 32 , I-20133 Milano , Italy.

Porphyrins are an extremely valuable class of molecules engaged in a variety of roles spanning from biology to optoelectronics. Manipulation of the chemical and physical properties of the inner cavity of porphyrins has been recognized as crucial for the exploitation of these systems in organic devices, particularly when porphyrins self-organize at the interface with a flat-on orientation of the macrocycle. Such an orientation has been mostly observed on metallic surfaces. Unfortunately, the physical-chemical properties of the molecules result in being largely perturbed due to the molecule-metal interaction. In addition, conducting substrates are unsuited to exploit electrically driven devices based on organic layers. To overcome these issues, we performed a topology-based analysis of insulating organic single crystal structures to identify a surface which (i) ensures easy exfoliation through mechanical methods, (ii) ensures epitaxial match with an overlayer of close-packed flat-on porphyrin molecules, and (iii) displays chirality. The outcome of this work is represented by a unique crystal of mixed 2,5-diketopiperazine and fumaric acid in a 1:1 ratio. We demonstrate that the (110) surface of this crystal fulfills the aforementioned requirements and, thanks to its peculiar subnanometric corrugations, allows one to grow uniaxially aligned monolayers of flat-on porphyrin molecules assembled through van der Waals interactions.
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http://dx.doi.org/10.1021/acs.nanolett.9b02067DOI Listing
August 2019

Combining Immunotherapy with Radiotherapy for the Treatment of Genitourinary Malignancies.

Eur Urol Oncol 2019 02 16;2(1):79-87. Epub 2018 Nov 16.

Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA.

Context: Immunotherapy drugs, particularly checkpoint inhibitors, have recently been approved by the Food and Drug Administration for various malignancies. Preclinical and early clinical data show that combining these agents with radiotherapy may produce an even more potent antitumor effect in the treatment of cancer.

Objective: To describe the rationale, available data, and emerging data on the use of combined immunotherapy and radiation therapy in the setting of genitourinary (GU) malignancies.

Evidence Acquisition: We performed a search of primary studies from PubMed/Medline that included combinations of the search terms "radiation therapy," "radiotherapy," "abscopal effect," "immunotherapy," "combined," and "combination."

Evidence Synthesis: Preclinical and clinical data support both immune-stimulating and immune-suppressing effects of radiotherapy. Preclinical and clinical studies investigating the combination of radiotherapy with immunotherapy, primarily in the setting of non-GU malignancies, have suggested efficacy and tolerability. Early randomized trials combining radiotherapy and immunotherapy have demonstrated success in lung cancer. Although a trial investigating combined immunotherapy and radiotherapy use for prostate cancer did not clearly improve survival, trials are ongoing in multiple GU malignancies to identify synergy between immunotherapy and radiotherapy. Several practical and technical questions remain about the optimal combination of radiotherapy and immunotherapy.

Conclusions: Preclinical and clinical trials show that the combination of the immunotherapy and radiation therapy has the potential to provide a synergistic effect in treating cancer, including GU malignancies, although more work is needed to uncover the mechanism and determine the optimal delivery of this treatment.

Patient Summary: This paper reviews evidence that immunotherapy drugs can be given together with radiation therapy to improve outcomes in cancers of the genitourinary tract. We find promising initial results and raise important questions that need to be answered before this type of treatment can be utilized successfully.
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http://dx.doi.org/10.1016/j.euo.2018.09.013DOI Listing
February 2019

Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy: Results from a Multi-Institutional Study.

Eur Urol 2019 10 22;76(4):443-449. Epub 2019 Feb 22.

Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Background: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial.

Objective: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics.

Design, Setting, And Participants: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1ng/ml at 1mo after surgery. Administration of concomitant HT was at the discretion of the treating physician.

Outcome Measurements And Statistical Analysis: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2).

Results And Limitations: Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9mo. At median follow-up of 93mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p=0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p=0.001; 0 vs ≥2, p<0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration.

Conclusions: The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT.

Patient Summary: We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT.
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http://dx.doi.org/10.1016/j.eururo.2019.02.004DOI Listing
October 2019

Helping patients make informed decisions. Two-year evaluation of the Gustave Roussy prostate cancer multidisciplinary clinic.

Clin Transl Radiat Oncol 2018 Aug 6;12:28-33. Epub 2018 Jul 6.

Gustave Roussy, Université Paris-Saclay, Département de Radiothérapie Oncologique, F-94800 Villejuif, France.

Objectives: The initial treatment decision for newly diagnosed non-metastatic prostate cancer is complex. Multiple valid approaches exist, without a clear and absolute consensus for every clinical scenario, and therefore specialist opinions may vary. Multidisciplinary consultations focusing on shared decision-making aim to provide an apposite tool for the initial treatment decision. We have evaluated the first two years of activity of the Gustave Roussy Prostate Cancer Multidisciplinary Clinic (PCMC), dedicated to the initial decision-making for non-metastatic prostate cancer.

Methods: PCMC consists of two consecutive specialist consultations with a urological surgeon and a radiation oncologist, followed by a dedicated Tumor Board discussion. A study questionnaire was addressed to all PCMC patients via postal mail. Medical notes and questionnaire responses of 195 eligible patients were analyzed.

Results: The questionnaire response rate was 69% (134 patients). Complete satisfaction rate was high (114 of 118 responders, 97%). Patients were offered new treatment options in 55% of cases, and felt better informed in 98% (122 of 125 responders). The double consultation was considered useful (124 of 129 responders, 96%). Reported feeling of active participation was significantly elevated (117 of 131 responders, 89%), while 46% of patients (57 of 125) modified their decision on the management of their prostate cancer following their PCMC consultation.

Conclusions: The experience of a multidisciplinary consultation in the initial management of non-metastatic prostate cancer renders high patient satisfaction, improves their appreciation of feeling better informed, promotes active participation and shared decision-making and strongly influences their final decision.
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http://dx.doi.org/10.1016/j.ctro.2018.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072649PMC
August 2018

Daily Versus Weekly Prostate Cancer Image Guided Radiation Therapy: Phase 3 Multicenter Randomized Trial.

Int J Radiat Oncol Biol Phys 2018 12 31;102(5):1420-1429. Epub 2018 Jul 31.

Department of Radiotherapy, APHP Henri Mondor Hospital, UPEC Créteil, France.

Purpose: The optimal frequency of prostate cancer image guided radiation therapy (IGRT) has not yet been clearly identified. This study sought to compare the safety and efficacy of daily versus weekly IGRT.

Materials And Methods: This phase 3 randomized trial recruited patients with N0 localized prostate cancer. The total IGRT doses in the prostate ranged from 70 Gy to 80 Gy, sparing the lymph nodes. Patients were randomly assigned (1:1) to 2 prostate IGRT frequency groups: daily and weekly (ie, on days 1, 2, and 3 and then weekly). The primary outcome was 5-year recurrence-free survival. Secondary outcomes included overall survival and toxicity. Post hoc analyses included biochemical progression-free interval, clinical progression-free interval, and other cancer-free interval.

Results: Between June 2007 and November 2012, 470 men from 21 centers were randomized into the 2 groups. Median follow-up was 4.1 years. There was no statistically significant difference in recurrence-free survival between the groups (hazard ratio [HR] = 0.81; P = .330). Overall survival was worse in the daily group than in the weekly group (HR = 2.12 [95% confidence interval (CI), 1.03-4.37]; P = .042). Acute rectal bleeding (grade ≥1) was significantly lower in the daily group (6%) (n = 14) than in the weekly group (11%) (n = 26) (P = .014). Late rectal toxicity (grade ≥1) was significantly lower in the daily group (HR = 0.71 [95% CI, 0.53-0.96]; P = .027). Biochemical progression-free interval (HR = 0.45 [95% CI, 0.25 - 0.80]; P = .007) and clinical progression-free interval (HR = 0.50 [95% CI, 0.24-1.02]; P = .057) were better in the daily group, whereas other cancer-free interval was worse in the daily group (HR = 2.21 [95% CI, 1.10-4.44]; P = .026).

Conclusions: Compared with weekly control, daily IGRT control in prostate cancer significantly improves biochemical progression-free and clinical progression-free interval, and rectal toxicity.
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http://dx.doi.org/10.1016/j.ijrobp.2018.07.2006DOI Listing
December 2018
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