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Additional file 1: Supplementary materials.

Background: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS). Materials and Methods: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8–10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis. Results: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0–5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50–0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49–0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse. Conclusion: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.

Background Perirectal spacers may be beneficial to reduce rectal side effects from radiotherapy (RT). Here, we present the impact of a hyaluronic acid (HA) perirectal spacer on rectal dose as well as spacer stability, long-term gastrointestinal (GI) and genitourinary (GU) toxicity and patient-reported outcome (PRO). Methods In this phase II study 81 patients with low- and intermediate-risk prostate cancer received transrectal injections with HA before external beam RT (78 Gy in 39 fractions). The HA spacer was evaluated with MRI four times; before (MR0) and after HA-injection (MR1), at the middle (MR2) and at the end (MR3) of RT. GI and GU toxicity was assessed by physician for up to five years according to the RTOG scale. PROs were collected using the Swedish National Prostate Cancer Registry and Prostate cancer symptom scale questionnaires. Results There was a significant reduction in rectal V70% (54.6 Gy) and V90% (70.2 Gy) between MR0 and MR1, as well as between MR0 to MR2 and MR3. From MR1 to MR2/MR3, HA thickness decreased with 28%/32% and CTV-rectum space with 19%/17% in the middle level. The cumulative late grade ≥ 2 GI toxicity at 5 years was 5% and the proportion of PRO moderate or severe overall bowel problems at 5 years follow-up was 12%. Cumulative late grade ≥ 2 GU toxicity at 5 years was 12% and moderate or severe overall urinary problems at 5 years were 10%. Conclusion We show that the HA spacer reduced rectal dose and long-term toxicity.

Sammendrag Problemstilling: Hvilke faktorer har innvirkning på utvidelse av mammografiscreening, og hvilke tiltak kan bli gjort for å kunne utvide mammografiscreening frem til 74 år? Hensikt: Det er uenigheter i forskningsmiljøet om mammografiscreening bør utvides til en eldre aldersgruppe. Hensikten med oppgaven er å belyse hvilke faktorer som påvirker utvidelse av Mammografiprogrammet, og hvilke tiltak som kan gjennomføres for å muliggjøre mammografiscreening frem til 74 år. Metode: Det ble benyttet litteraturstudie som metode for å besvare problemstillingen. Seks studier dannet grunnlaget for en analysering av hvilke faktorer som påvirker utvidelse av mammografiscreening til en eldre aldersgruppe. Faktorer som blir belyst i denne oppgaven er: mortalitet, overdiagnostisering, falske-positive funn, og kostnadseffektivitet. Resultat: Overdiagnostisering og falske-positive funn blir ansett på som harms, og blir betraktet som de største grunnene for å ikke utvide mammografiscreening. Derimot blir redusert risiko for mortalitet betraktet som benefit. Utvidelse til 74 år reduserte mortalitet, men økte sannsynlighetene for overdiagnostisering og falske-positive funn. Kostnadene for behandling av cancer mammae økte med cancer stadiet, som påvirker både sykehus og pasient. Ved å utvide den øvre aldersgruppen til 74 år, økte kostnadene marginalt grunnet ekstra screeningkostnader, men dette ble balansert av bedre resultater. Konklusjon: Mortalitetsraten sank etter inkludering av eldre kvinner i mammografiscreening. Ved å utvide mammografiscreening vil flere falske-positive funn og tilfeller med overdiagnostisering oppstå, men siden eldre kvinner er mer hormonbetinget og har tidligere undersøkelser for sammenligning, kan det bli antatt at det vil oppstå mindre tilfeller med harms. Kostnadene for å utvide mammografiscreening var lavere enn kostnadene for behandling av cancer mammae i et senere stadium. Regulering etter risikonivå for kvinner og triennal mammografiscreening kan være alternativer for den biennale mammografiscreeningen som blir benyttet i dag. Nøkkelord: cancer mammae, mammografiscreening, utvidelse, harm to benefit-ratio, kostnad Antall ord: 9275 Abstract Thesis: Which factors contribute to expanding mammographic screening, and what measures can be done to be able to extend mammography screening to the age of 74? Purpose: There are disagreements within the research community regarding if mammography screening should be extended to an older age group. The purpose of this thesis is to elucidate the factors influencing the extension of BreastScreen Norway, and identify measures that can be implemented to enable mammography screening up to the age of 74. Method: A literature review was used as the methodological approach to answer the thesis question. Six studies constituted the basis for an analysis of the factors influencing the expansion of mammography screening to an older age group. The factors in this review are defined as: mortality, overdiagnosis, false-negative findings, and cost-effectiveness. Results: Overdiagnosis and false-positive findings are considered as harms, and are regarded as the primary reasons for not expanding mammography screening. However, reduced mortality risk is considered a benefit. Extending mammography screening to the age of 74 resulted in reduced mortality, but increased the chances of overdiagnosis and false-positive findings. The costs of treating cancer mammae increased with cancer stage, affecting both the hospital and patient. By extending the upper age group to 74 years, the costs increased marginally due to extra screening costs, but this was balanced by better outcomes. Conclusion: The mortality rate was reduced after the inclusion of older women in mammography screening. By extending mammography screening, more false-positive findings and cases of overdiagnosis will occur, but since older women are more hormone-dependent and have previous exams for comparison, it can be assumed that there will be fewer cases of harms. The costs of extending mammography screening were lower than the costs of treating cancer mammae at a later stage. Regulating according to women’s risk levels and triennal mammography screening could potentially be alternatives to the current biennal mammography screening that is practiced today. Keywords: cancer mammae, mammography screening, extending, harm to benefit-ratio, cost Number of words: 9275

Sammendrag Problemstilling: Hvilken av undersøkelsene digital mammografi og digital bryst tomosyntese vil gi høyest deteksjon av tumorer i et screeningprogram, og hvilke faktorer kan påvirke deteksjonsraten? Hensikt: Hensikten med denne oppgaven var å se på deteksjonsraten av tumorer ved digital mammografi og digital bryst tomosyntese i et screeningprogram, og å se på hvilke faktorer som kan påvirke deteksjonsraten. Metode: Det er blitt benyttet en kvalitativ litteraturstudie for å besvare denne oppgaven. Ved hjelp av PICO skjema har det blitt funnet søkeord som har blitt tatt i bruk til å finne artikler i ulike databaser. Videre har vi hentet inn data som har blitt analysert og tolket for å kunne finne ut om digital bryst tomosyntese har en høyere deteksjonsrate enn digital mammografi. Resultat: Vi har oppsummert resultatene på deteksjonsrate ved digital mammografi og digital bryst tomosyntese fra fem ulike artikler. Det er flere faktorer som kan påvirke deteksjonsraten og faktorene vi har fokusert på i denne oppgaven er alder, krefttyper, sensitivitet og spesifisitet, tilbakekalling og førstegangs screening. Resultatene blir presentert i form av tekst og tabeller. Konklusjon: Vi konkluderer med at det er sannsynlig at digital bryst tomosyntese vil gi en høyere deteksjon av tumorer enn digital mammografi i et screeningprogram. Det er varierende i hvor stor grad faktorene påvirker deteksjonsraten. Hva slags type alder, kreft, sensitiviteten og førstegangs screenede er faktorer som påvirker deteksjonsraten. Når det kommer til spesifisitet og tilbakekalling er det vanskelig å komme med en sikker konklusjon da det ikke er nok data på dette. Det vil derfor være gunstig å fortsette å forske på tema. Nøkkelord: Digital mammografi, digital bryst tomosyntese, screening, deteksjonsrate, innvirkende faktorer Abstract Topic/research question: Which one of the examinations digital mammography and digital breast tomosynthesis will give the highest detection of tumors in a screening program, and which factors can affect the detection rate? Purpose: The purpose of this study was to look at the detection rate of tumors in digital mammography and digital breast tomosynthesis in a screening program, and to look at which factors that can affect the detection rate. Method: We have used a quantitative literature review to answer these factors. By using a PICO form we found keywords that have been used to find articles in different databases. Further we collected and analyzed data to find out if digital breast tomosynthesis has a higher detection rate than digital mammography. Results: We have compared the detection rate results between digital mammography and digital breast tomosynthesis from five different articles. There are several factors that can affect the detection rate and the factors we have focused on in this study is age, types of cancers, sensitivity and specificity, recall rate and first time screening. The results are presented in text and tables. Conclusion: We have concluded that it is likely that digital breast tomosynthesis will provide a higher detection of tumors than digital mammography in a screening program. The extent to which the factors affect the detection rate varies. Age, what type of cancer, sensitivity and first time screening are factors that affect the detection rate. When it comes to specificity and recall rate it is difficult to come with a conclusion because there is not enough data on this. It will therefore be beneficial to continue to research this topic. Keywords: Digital mammography, digital breast tomosynthesis, screening, detection rate, influential factors