The Swedish national guidelines on prostate cancer, part 1: early detection, diagnostics, staging, patient support and primary management of non-metastatic disease

Objective: There is now an unprecedented amount of evidence to consider when revising prostate cancer guidelines. We believe that there is a value in publishing summaries of national clinical guidelines in English for others to read and comment on. Methods: This is part 1 of a summary of the Swedish prostate cancer guidelines that were published in June 2022. It covers the early detection, diagnostics, staging, patient support and management of the non-metastatic disease. Part 2 covers recurrence after local treatment and management of the metastatic disease. Results: The 2022 Swedish guidelines include several new recommendations: rectal iodine-povidone to reduce post-biopsy infections, external beam radiation with focal boost to the tumour, use of a pre-rectal spacer to reduce rectal side effects after external beam radiotherapy in some expert centres, 6 months’ concomitant and adjuvant rather than neoadjuvant and concomitant hormonal treatment together with radiotherapy for unfavourable intermediate and high-risk disease, and adjuvant abiraterone plus prednisolone together with a GnRH agonist for a subgroup of men with very high-risk disease. The Swedish guidelines differ from the European by having more restrictive recommendations regarding genetic testing and pelvic lymph node dissection, the risk group classification, recommending ultra-hypofractionated (7 fractions) external radiotherapy for intermediate and selected high-risk cancers, by not recommending any hormonal treatment together with radiotherapy for favourable intermediate-risk disease, and by recommending bicalutamide monotherapy instead of a GnRH agonist for some patient groups. Conclusions: The 2022 Swedish prostate cancer guidelines include several new recommendations and some that differ from the European guidelines

The Swedish national guidelines on prostate cancer, part 2 : recurrent, metastatic and castration resistant disease

Objective: There is now an unprecedented amount of evidence to consider when revising prostate cancer guidelines. We believe that there is a value in publishing summaries of national clinical guidelines in English for others to read and comment on. Methods: This is part 2 of a summary of the Swedish prostate cancer guidelines that were published in June 2022. This part covers recurrence after local treatment and management of metastatic and castration resistant disease. Part 1 covers early detection, diagnostics, staging, patient support and management of non-metastatic disease. Results: The 2022 Swedish guidelines include several new recommendations. Among these is a recommendation of a period of observation with repeated PSA tests for patients with approximately 10 years’ life expectancy who experience a BCR more than 2–5 years after radical prostatectomy, to allow for estimating the PSA doubling time before deciding whether to give salvage radiotherapy or not. Recent results from the PEACE-1 trial led to the recommendation of triple-treatment with a GnRH agonist, abiraterone plus prednisolone and 6 cycles of docetaxel for patients with high-volume metastatic disease who are fit for chemotherapy. The Swedish guidelines differ from the European ones by having more restrictive recommendations about genetic testing of and high-dose zoledronic acid or denosumab treatment for men with metastatic prostate cancer, and by recommending considering bicalutamide monotherapy for selected patients with low-volume metastatic disease. Conclusions: The 2022 Swedish prostate cancer guidelines include several new recommendations and some that differ from the European guidelines

Socioeconomic inequality in prostate cancer diagnostics, primary treatment, rehabilitation, and mortality in Sweden

We designed a nationwide study to investigate the association between socioeconomic factors (household income and education) and different aspects of prostate cancer care, considering both individual- and neighbourhood-level variables. Data were obtained from Prostate Cancer data Base Sweden (PCBaSe), a research database with data from several national health care registers including clinical characteristics and treatments for nearly all men diagnosed with prostate cancer in Sweden. Four outcomes were analysed: use of pre-biopsy magnetic resonance imaging (MRI) in 2018–2020 (n = 11,843), primary treatment of high-risk non-metastatic disease in 2016–2020 (n = 6633), rehabilitation (≥2 dispensed prescriptions for erectile dysfunction within 1 year from surgery in 2016–2020, n = 6505), and prostate cancer death in 7770 men with high-risk non-metastatic disease diagnosed in 2010–2016. Unadjusted and adjusted odds and hazard ratios (OR/HRs) with 95% confidence intervals (CIs) were calculated. Adjusted odds ratio (ORs) comparing low versus high individual education were 0.74 (95% CI 0.66–0.83) for pre-biopsy MRI, 0.66 (0.54–0.81) for primary treatment, and 0.82 (0.69–0.97) for rehabilitation. HR gradients for prostate cancer death were significant on unadjusted analysis only (low vs. high individual education HR 1.41, 95% CI 1.17–1.70); co-variate adjustments markedly attenuated the gradients (low vs. high individual education HR 1.10, 95% CI 0.90–1.35). Generally, neighbourhood-level analyses showed weaker gradients over the socioeconomic strata, except for pre-biopsy MRI. Socioeconomic factors influenced how men were diagnosed with prostate cancer in Sweden but had less influence on subsequent specialist care. Neighbourhood-level socioeconomic data are more useful for evaluating inequality in diagnostics than in later specialist care

A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome : No Evidence of Benefit, Supported by Epidemiology and In Vitro Data

Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response. Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care. Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders. Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19