Buteau JP, Moon D, Fahey MT
… +35 more, Roberts MJ, Ayati N, Papa N, Murphy DG, Kasivisvanathan V, Dhillon HM, Du YT, Dundee P, Foudoulis J, Hennes D, Hutton AC, Idiare J, Jack G, Kamath S, Lee SN, Lee SF, Lee ST, Leslie S, Levy SM, Link E, Mitchell C, Morigi JJ, Nguyen A, Olphert J, Patel MI, Pattison DA, Pearce A, Perera M, Thanigasalam R, Thomson A, Yaxley J, Thompson J, Hofman MS, Emmett L, PRIMARY2 Trial Investigators
BACKGROUND: MRI is recommended for men with clinical suspicion of significant prostate cancer. Those with high clinical risk but non-suspicious or equivocal MRI often undergo prostate biopsy, but have a low likelihood of...BACKGROUND: MRI is recommended for men with clinical suspicion of significant prostate cancer. Those with high clinical risk but non-suspicious or equivocal MRI often undergo prostate biopsy, but have a low likelihood of clinically significant prostate cancer, and a high incidence of clinically insignificant prostate cancer. We aimed to investigate whether gallium-68 ([Ga]Ga)-prostate-specific membrane antigen (PSMA)-11 PET-CT could reduce the number of people requiring prostate biopsy and limit biopsy to targeted cores, without compromising clinically significant prostate cancer diagnosis. METHODS: In this multicentre, non-inferiority, phase 3, randomised controlled trial, done at at seven Australian hospitals, we recruited biopsy-naive participants with clinical suspicion of significant prostate cancer, equivocal (Prostate Imaging-Reporting and Data System [PI-RADS] 3) or non-suspicious (PI-RADS 2) MRI but high clinical risk (eg, prostate-specific antigen [PSA] density of >0·1 ng/mL/mL, strong family history of prostate cancer, abnormal digital rectal examination, BRCA mutation, PSA >10 ng/mL, PSA doubling time <36 months, or PSA velocity >0·75 ng/mL per year), PSA of 20 ng/mL or less, and clinical T2 disease or less. Participants were randomly assigned (1:1) using a centralised web-based system to undergo [Ga]Ga-PSMA-11 PET-CT (experimental group) or systematic transperineal prostate biopsy (control group), using block sizes of two or four and stratification by study site. There was no masking for participants or investigators. Participants with positive [Ga]Ga-PSMA-11 PET-CT (PRIMARY score 3-5) underwent PSMA-PET-targeted transperineal prostate biopsies, whereas those with a negative result (PRIMARY score 1-2) avoided biopsy. The co-primary outcomes were the proportion of participants with clinically significant prostate cancer, defined as a Gleason score of 3 + 4 (≥10% pattern 4) or higher, and the proportion of participants in the [Ga]Ga-PSMA-11 PET-CT group who avoided biopsy within 6 months of random assignment. A two-sided 95% Wald CI based on a binomial model was used to estimate the risk difference in the proportion of participants with clinically significant prostate cancer (non-inferiority margin 10%) and to estimate the proportion of participants in the experimental group who had avoided biopsy 6 months after random assignment (20% threshold), analysed based on intention to treat. This trial is registered with ClinicalTrials.gov, NCT05154162, and participant follow-up is ongoing. FINDINGS: Between March 2, 2022, and Aug 24, 2025, 660 eligible male participants were enrolled and had a median age of 61 years (IQR 56-66), a median PSA of 5·2 ng/mL (4·0-7·0), and a median PSA density of 0·13 ng/mL/mL (0·09-0·17). There were PI-RADS 2 in 335 (51%) participants and PI-RADS 3 in 325 (49%) participants. Ethnicity data were not collected. 329 (50%) were assigned to the control group with systematic transperineal prostate biopsy, and 331 (50%) were assigned to the experimental group with [Ga]Ga-PSMA-11 PET-CT. The proportion of participants with clinically significant prostate cancer in the experimental group (39 [12%] of 331) was non-inferior to the control (51 [16%] of 329; difference -3·7% [95% CI -8·9 to 1·5%]; p=0·0093). Use of [Ga]Ga-PSMA-11 PET-CT avoided biopsy in 163 (49%) of 331 participants (95% CI 44 to 55%; p <0·0001). After prostate biopsy, participants reported similar proportions of pain (33 [21%] in the experimental group vs 62 [21%] in the control group), haematuria (60 [38%] vs 126 [43%]), and haematospermia (77 [48%] vs 133 [45%]). INTERPRETATION: [Ga]Ga-PSMA-11 PET-CT could have the potential to improve the diagnostic pathway of patients with a high clinical risk but non-suspicious or equivocal prostate MRI. Further research, including health-economic analyses and validation with other PSMA radiopharmaceuticals, are needed to confirm the clinical implementation and generalisability of this approach. FUNDING: Prostate Cancer Foundation, National Health and Medical Research Council, St Vincent's Curran Foundation, and Peter MacCallum Cancer Foundation.
Morgan E, Bardot A, Langselius O
… +44 more, Rutherford MJ, Elkader HA, Bennett D, Brennan A, Bucher O, Butler J, Cameron DA, Canfell K, Chiam K, Chiarelli A, Creighton N, De P, Evans S, Fitzpatrick D, Guren MG, Hannah J, Huws DW, Jackson CGCA, Kønig SM, Kumar E, Larønningen S, Lawler M, Liu Q, McClure C, Mehmood A, Mitchell H, Morrison DS, Murray D, Norwood T, Phillips KAM, Ransom D, Shack L, Smits S, Saint-Jacques N, Marvelde LT, Tran D, Turner D, Ursin G, Vernon S, Walker MJ, Woods RR, Zhang B, Bray F, Soerjomataram I
Lancet Oncol
· 2026 Jun · PMID 42225103
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BACKGROUND: The COVID-19 pandemic had an impact on cancer services globally. There is a crucial need to understand how the incidence and stage of major cancer types were affected internationally. We aimed to assess these...BACKGROUND: The COVID-19 pandemic had an impact on cancer services globally. There is a crucial need to understand how the incidence and stage of major cancer types were affected internationally. We aimed to assess these metrics in seven countries within the International Cancer Benchmarking Partnership. METHODS: This population-based study used data on 2·6 million patients diagnosed with primary cancers of the colon, rectum, lung, prostate, female breast, ovary, and melanoma of the skin, between Jan 1, 2015, and Dec 31, 2020. Data were collected from cancer registries in 18 jurisdictions from seven countries participating in the International Cancer Benchmarking Partnership; Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK. The main outcomes of monthly cases and age-standardised incidence rates by site during the pandemic (April 1 to Dec 31, 2020) were compared with predictions for the same year based on pre-pandemic trends (Jan 1, 2015, to Dec 31, 2019). FINDINGS: Between April 1, and Dec 31, 2020, 55 713 (16%) of 347 666 expected cases were predicted to be missing, with the largest deficits seen for prostate cancer (24%), female breast cancer (18%), and melanoma (18%), and the smallest deficits seen for ovarian (4%) and lung cancer (8%). The largest difference between observed and predicted incidence rates for prostate cancer was seen in the UK (164·9 per 100 000 person-years predicted vs 101·4 per 100 000 person-years observed) and the smallest difference seen in Norway (164·1 vs 168·4). Reductions in incidence were greatest from April 1, to July 31, versus from Aug 1, to Dec 31, in 2020. The percentage deficits between observed and predicted cases were 54% (UK) and 36% (Ireland) for prostate cancer, 40% (UK) and 34% (Ireland) for breast cancer, and 40% (UK) and 35% (Canada) for melanoma. INTERPRETATION: The pandemic's greatest impact was during the first few months of societal lockdowns in 2020 when barriers in access to health care were greatest. Further research is needed to understand whether patients with a missed diagnosis were diagnosed at a later date and if they presented at a later stage. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Higher Education Authority North South Research Programme, Health Data Research UK; Te Aho o Te Kahu, Cancer Control Agency New Zealand; New Zealand Cancer Society; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network.
Baudin E, Durand A, Beron A
… +28 more, Smith D, Déandreis D, Taieb D, Ansquer C, Dierickx L, Deshayes E, Hentic O, Moalla S, Menu Y, Lebtahi R, Assenat E, Touchefeu Y, Guimbaud R, Dahan L, Lamartina L, Cheurfa N, Quak E, Bouhier-Leporrier K, Haissaguerre M, Hindie E, Cao CD, Lombard-Bohas C, Jannin A, Walter T, Ducreux M, Chaib S, Hadoux J, Foulon S
BACKGROUND: To our knowledge, no randomised trial with peptide receptor radionuclide therapy has been done in patients with metastatic pancreatic neuroendocrine tumours. We aimed to evaluate the antitumour activity and s...BACKGROUND: To our knowledge, no randomised trial with peptide receptor radionuclide therapy has been done in patients with metastatic pancreatic neuroendocrine tumours. We aimed to evaluate the antitumour activity and safety of [Lu]Lu-dota-tate in this setting. METHODS: OCLURANDOM is a randomised, open-label, non-comparative, phase 2 trial conducted in ten academic centres in France. Patients aged 18 years and older with pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1) using web-based software to receive intravenous [Lu]Lu-dota-tate (7·4 GBq every 8 weeks up to four cycles) with concomitant amino acid infusion or oral sunitinib (37·5 mg once daily). Amino acid infusion was for at least 4 h starting 30 min before [Lu]Lu-dota-tate infusion and included 16·8 g of arginine and 22 g of lysine in 2 L until May, 2018, and, from that date, a solution of 25 g of arginine and 25 g of lysine in 2 L. Randomisation was stratified according to Ki-67, liver involvement, and previous therapies. The primary endpoint was progression-free survival at 12 months assessed by real-time central review using Response Evaluation Criteria in Solid Tumours version 1.1 in the intention-to-treat population. Cross-over was allowed. Adverse events in the as-treated population were assessed continuously during the active phase of treatment and then every 3 months. Patients and the public were not involved in the design, conduct, reporting, or dissemination plans of this research. This trial was registered with ClinicalTrials.gov, NCT02230176, and is closed to enrolment. FINDINGS: Between Feb 13, 2015, and July 16, 2020, 84 patients were enrolled and randomly assigned to the [Lu]Lu-dota-tate group (n=41) or the sunitinib group (n=43). 44 (52%) patients were women and 40 (48%) were men. Median follow-up was 72·5 months (IQR 61·4-88·4). Progression-free survival rate at 12 months was 33 (80·5% [90% CI 67·5-89·9]) of 41 patients in the [Lu]Lu-dota-tate group versus 18 (41·9% [29·1-55·5]) of 43 patients in the sunitinib group. Grade 3-4 adverse events occurred in 18 (44%) of 41 patients in the [Lu]Lu-dota-tate group and 31 (72%) of 43 patients in the sunitinib group. The most common grade 3-4 adverse events for all treatment groups were neutropenia (two [5%] of 41 in the [Lu]Lu-dota-tate group vs 13 [30%] of 43 in the sunitinib group) and hypertension (four [10%] in the [Lu]Lu-dota-tate group vs eight [19%] in the sunitinib group). Drug-related serious adverse events occurred in six (15%) patients in the [Lu]Lu-dota-tate group (transaminase increase, neutropenia, thrombosis, and fever) and ten (23%) in the sunitinib group (gastrointestinal, general disorders, and sepsis). There was a 10·3-point (95% CI 2·4-18·2) difference in the Global Health Status score between the two groups in favour of [Lu]Lu-dota-tate. Late adverse events (grade 2 or worse) were reported in 24 (60%) patients in the [Lu]Lu-dota-tate group and in three (43%) of seven patients in the sunitinib group. One treatment-related death (acute leukaemia) occurred in the [Lu]Lu-dota-tate group. INTERPRETATION: Using sunitinib as an internal control, our results show clinically significant antitumour efficacy of [Lu]Lu-dota-tate in pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours, and a better quality of life during the treatment phase. Late adverse events were reported in the [Lu]Lu-dota-tate group that might affect the tolerance of subsequent lines of treatment. FUNDING: French Ministry of Health, through the National Institute for Cancer.
BACKGROUND: About 30% of men with localised prostate cancer undergoing radiotherapy with curative intent have disease recurrence associated with progression-related symptoms and substantial toxicity of salvage therapies....BACKGROUND: About 30% of men with localised prostate cancer undergoing radiotherapy with curative intent have disease recurrence associated with progression-related symptoms and substantial toxicity of salvage therapies. Previous studies with aglatimagene besadenovec (CAN-2409, hereafter referred to as aglatimagene) showed synergy with radiation and immune-mediated cytotoxicity in patients with prostate cancer. We aimed to assess whether addition of aglatimagene plus prodrug (valacyclovir) to standard-of-care external beam radiation therapy (EBRT) could improve disease-free survival in this population. METHODS: We conducted a phase 3, randomised, double-blind, placebo-controlled trial at 51 medical centres (26 community and 25 institutional or military) across the USA and Puerto Rico in patients with intermediate or high-risk prostate cancer. Patients aged at least 18 years who were planning to undergo EBRT and with an Eastern Cooperative Oncology Group score of 0-2 were eligible. Patients were randomly assigned (2:1) via central block-randomisation to receive either three courses of intraprostatic aglatimagene (5 × 10 viral particles) plus valacyclovir or placebo plus valacyclovir, with randomisation stratified by risk category and androgen deprivation therapy (ADT) use. Patients received standard-of-care EBRT (78 Gy in 2 Gy fractions) or hypofractionated EBRT (60 Gy in 3 Gy fractions or 70 Gy in 2·5 Gy fractions) with optional ADT. The primary endpoint was disease-free survival, defined as time-from-randomisation to prostate cancer recurrence or death in the intent-to-treat population (all randomly assigned patients). Safety was assessed in all individuals who received at least one injection. The trial is registered at ClinicalTrials.gov, NCT01436968, and long-term follow-up is ongoing. FINDINGS: Between Feb 21, 2012, and Sept 9, 2021, 745 men (591 [79%] White, 121 [16%] Black) were randomly assigned to receive aglatimagene plus valacyclovir (n=496) or placebo plus valacyclovir (n=249). After a median follow-up of 50·3 months (IQR 35·2-63·3), median disease-free survival was not reached (95% CI 121·78 to not reached) in the aglatimagene plus valacyclovir group versus 86·1 (IQR 29·7-143·0) months in the placebo plus valacyclovir group (hazard ratio 0·70, 95% CI 0·52-0·94; p=0·016). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 40 (8%) of 479 patients in the aglatimagene group and 17 (7%)of 232 patients in the placebo group. The most common TEAE of grade 3 or worse was acute kidney injury in both the aglatimagene group (nine [2%] of 479 patients) and the placebo group (four [2%] of 232 patients). Serious adverse events occurred in 28 (6%) of 479 patients in the aglatimagene group and 17 (7%) of 232 in the placebo group. Treatment-related serious adverse events occurred in eight (2%) patients in the aglatimagene group (four acute kidney injury, two pyrexia, and one each influenza-like symptoms and urinary retention) and five (2%) in the placebo group (four acute kidney injury, and one each increased creatinine levels and skin rash; one patient reported two serious adverse events). No treatment-related deaths were reported. INTERPRETATION: Aglatimagene plus valacyclovir was associated with longer disease-free survival than placebo plus valacyclovir when added to standard of radiotherapy for the treatment of localised prostate cancer, offering a meaningful benefit without increasing clinically significant toxicity. FUNDING: Candel Therapeutics and US National Institutes of Health.