Le cancer de la prostate est une maladie très hétérogène dont le développement est principalement médié par l'action du récepteur aux androgènes. Ceci a donc résulté en une émergence de thérapies ciblant spécifiquement la voie du récepteur aux androgènes afin de traiter la maladie. Toutefois, tous les patients traités avec ces stratégies thérapeutiques développeront une résistance à celle-ci par des mécanismes dépendants et indépendants du récepteur aux androgènes. Comme la réponse clinique peut seulement être évaluée trois mois après le début de la thérapie, il est primordial de développer un test permettant de prédire précocement la réponse aux traitements. Ceci permettrait d'orienter, le plus rapidement possible, les patients réfractaires vers des thérapies alternatives. L'objectif principal de cette thèse était donc de développer des outils moléculaires afin d'étudier la réponse thérapeutique et l'impact des différents mécanismes de résistance sur celle-ci. Mes travaux présentés dans le chapitre 1 ont démontré qu'il était possible de suivre dynamiquement par imagerie à bioluminescence la réponse aux traitements de cellules cancéreuses prostatiques en immobilisant les cellules isolées grâce à un biofilm de matrice extracellulaire. Afin de suivre la réponse aux anti-androgènes spécifiquement dans les cellules cancéreuses prostatiques, un premier biosenseur basé sur l'activité de deux promoteurs spécifiques a été développé dans le chapitre 2. Celui-ci intègre l'activité du promoteur PCA3, qui est spécifique au cancer de la prostate, et du promoteur PSEBC, qui est sensible aux androgènes, afin de générer un signal luminescent quantitatif et représentatif de la réponse androgénique. Grâce à ce système, la sensibilité de cellules cancéreuses prostatiques isolée de patients naïfs et résistants aux anti-androgènes a pu être corrélée avec la réponse clinique des patients. L'applicabilité de ce biosenseur est toutefois limitée aux cellules exprimant un récepteur aux androgènes transcriptionnellement actif. Un deuxième système exploitant les capacités de la Cre recombinase à décoder l'activité des promoteurs PCA3 et PSEBC en deux signaux bioluminescents spectralement distincts a donc été développé dans le chapitre 3. Ce deuxième système combine tous les avantages et capacités du premier, tout en permettant la détection de cellule n'ayant pas d'activité androgénique. Celui-ci permet donc de visualiser des mécanismes de résistance complexes qui peuvent être indépendants ou dépendants du récepteur aux androgènes et qui collaborent pour échapper aux effets inhibiteurs des anti-androgènes. Les outils développés peuvent cibler et détecter avec précision les cellules épithéliales de cancer de la prostate ainsi que leur réponse aux thérapies. Les travaux de cette thèse ont ainsi ouvert la voie à de nouvelles techniques et connaissances sur des méthodes de diagnostic et de pronostic pour le cancer de la prostate. Ultimement, cela permettra d'améliorer le choix des traitements disponibles afin d'augmenter la qualité de vie des patients. / Prostate cancer is a very heterogeneous disease and its growth is driven mainly by the androgen receptor transcriptional activity. This has led to the development of androgen deprivation therapy as the main treatment of this disease to prevent its progression. However, almost all patients receiving these therapies will develop resistance through the acquisition of androgen receptor dependent and independent mechanisms. The challenge of prostate cancer management is largely due to drug-refractory sub-populations with in heterogeneous tumors. Only few biomarkers have been validated for clinical use and none of them address complex anti-androgens response heterogeneity. The main objective of this thesis was to develop bioluminescence imaging systems to detect and monitor prostate cancer cells therapeutic response. In chapter 1, we have developed an extracellular matrix biofilm coating method to dynamically follow by bioluminescence imaging heterogenous treatment response of prostate cancer cells. In chapter 2, a first biosensor based on the activity of two specific promoters was developed to monitor antiandrogens response specifically in prostate cancer cells. This system integrates a transcriptional amplification system and the activities of the PCA3 and PSEBC gene promoters as a single output driving the firefly luciferase gene reporter. The PCA3 promoter provides the specificity to PCa cells, while the PSEBC promoter measures AR transcriptional activity. When tested on different cohorts of patients from primary PCa to mCRPC, our method could discriminate the overall response of a patient to antiandrogens. However, the applicability of this biosensor is limited to cells expressing a transcriptionally active androgen receptor. A second system exploiting the capacities of Cre recombinase and decoding PCA3 and PSEBC promoter activity in two spectrally distinct bioluminescent signals was therefore developed in chapter 3. This second system combines all the advantages and capacities of the first system, but also allows the detection of prostate cancer cells with no androgenic activity. This method visualizes complex androgen receptor independent and dependent resistance mechanisms and their interactions together to escape from antiandrogen inhibitory effects. The tools developed in this thesis can specifically target and detect prostate cancer cells and their response to therapies. Thus, they have the potential to play an important role in patients therapeutic management and therefore improve their overall survival.

The purpose of this study was to examine the relationships between stigma, quality of life (QoL), and relationships satisfaction for prostate cancer (PCa) survivors and their intimate and/or romantic partners. The investigator tested a theoretical model that stigma (as measured by the Social Impact Scale [SIS; Fife & Wright, 2000]) influenced QoL (as measured by the Functional Assessment of Cancer Therapy – Prostate [FACT-P; Esper et al., 1997] and the Functional Assessment of Cancer Therapy – General Population [FACT-GP; Cella et al., 1993]) and relationship satisfaction (as measured by the Couples Satisfaction Index [CSI; Funk & Rogge, 2007]) for both PCa survivors and their partners (N = 72 couples). The investigator hypothesized that stigma would have a negative influence on both QoL and relationship satisfaction. Further, exploratory research questions pertained to the influence of race on stigma, QoL, and relationship satisfaction, as well as examining difference in experiences of stigma based on demographic variables (e.g., age and income). The results of the structural equation model analyses identified that stigma negatively influenced QoL (R2 = .84, p < .05) and relationship satisfaction (R2 = .19, p < .05) for both PCa survivors and their partners. Race did not have statistically significant (p > .05) relationships with stigma, QoL, or relationship satisfaction and stigma was not found to be statistically different (p > .05) based on demographic variables. Implications of the results of the study include (a) practical implications for PCa survivors and their partners; (b) strategies for effective individual, group, and couples-based counseling; (c) need for counselor educators to prepare counselors to work with medically ill populations and cancer survivors; (d) PCa stigma instrument development; and (e) the necessity to examine research with couples in a dyadic fashion.

The glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin (PRSS8) is expressed at the apical membrane surface of epithelial cells and acts as a suppressor of tumor invasion when re-expressed in highly invasive human prostate and breast cancer cell lines. To better understand the molecular mechanisms underlying the anti-invasion phenotype associated with prostasin re-expression in prostate cancer cells, we expressed wild-type human prostasin or a serine active-site mutant prostasin in the PC-3 human prostate carcinoma cells. Molecular changes were measured at the mRNA and the protein levels. The expression of several invasion-promoting molecules is regulated by prostasin re-expression, mediated by a protein-level down-regulation of the epidermal growth factor receptor (EGFR). As a result, the cellular response to EGF was reduced as shown by the down-regulation of EGF-stimulated Erk1/2 phosphorylation. The expression of Slug, urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and granulocyte-macrophage colony stimulating factor (GM-CSF) was also down-regulated by prostasin re-expression in the PC-3 cells. Co-expression of prostasin and its activating protease matriptase with EGFR in FT-293 cells induces an apparent proteolytic cleavage of the EGFR in the extracellular domain at two specific sites, generating two N-terminally truncated EGFR fragments, named EGFR135 and EGFR110. The EGFR110 is constitutively tyrosine-phosphorylated, and in its presence the phosphorylation of downstream signaling molecules including Erk1/2 and Akt is increased under serum-free conditions. Neither EGFR135 nor EGFR110 is responsive to EGF stimulation. Deletions of the EGFR extracellular domain (ECD) were generated to map the matriptase-prostasin cleavage sites. Two candidate sites were localized to regions AA1-273 and AA273-410. These data support a mechanism of action for the matriptase-prostasin epithelial extracellular serine protease activation cascade by proteolytically modulating the EGF-EGFR signaling. Prostasin gene expression is down-regulated in high-grade and hormone-refractory prostate cancers. We investigated the mechanisms by which androgens regulate prostasin expression in the prostate and prostate cancer. We treated the LNCaP human prostate cancer cells with dihydrotestosterone (DHT) and measured the mRNA expression of prostasin and potential transcription regulators of prostasin predicted by interrogation of the prostasin gene promoter sequence. Prostasin mRNA expression in the LNCaP cells was not responsive to DHT treatment. DHT marginally up-regulated mRNA expression of SREBP-1c, SREBP-2, and SNAIL, but not SREBP-1a, while dramatically increased SLUG mRNA expression, in a dose-dependent manner. Co-transfection of a prostasin promoter-reporter and SREBP cDNA in HEK-293 cells resulted in stimulation of the promoter activity at ~2 fold by SREBP-1c, and up to 6 fold by SREBP-2; while co-transfection with SNAIL or SLUG cDNA resulted in repression of the promoter activity to 43% or 59%, respectively. Co-transfection of the SLUG cDNA negated SREBP-2 s stimulation of the prostasin promoter in a dose-dependent manner. Transfection of an SREBP-2 cDNA in HEK-293 and DU-145 cells resulted in up-regulation of the endogenously expressed prostasin while transfection of a SLUG cDNA in the LNCaP cells repressed prostasin expression. Multiple SREBP-2 binding sites, known as sterol regulatory elements (SRE s), were identified at positions -897, -538, +8, +71, and +98 (named SRE-897, SRE-538, SRE+8, SRE+71, and SRE+98) in the human prostasin gene promoter. Mutagenesis of the five SRE s was carried out to evaluate their roles in SREBP-2 up-regulation of prostasin. SRE+98, a novel functional sterol regulatory element was found to be the major site for the stimulatory response of prostasin gene expression to SREBP-2. CONCLUSIONS: Prostasin regulates the expression of several invasion-promoting molecules in prostate cancer cells by down-modulating the EGF-EGFR signaling pathway. Active prostasin induces proteolytic cleavage in the EGFR ECD at two specific sites. One of the N-terminally truncated EGFR, the EGFR110 is auto-phosphorylated along with increased phosphorylation of downstream signaling molecules. The effect of the androgen DHT on prostasin expression in prostate cells is mediated via SREBP s, which stimulate the promoter, and Slug, which represses the promoter. Slug is up-regulated by DHT and EGF, providing a molecular mechanism by which epithelial cell-specific genes are silenced during prostate cancer development and progression.

LIM kinase 1 (LIMK1) is a unique dual specificity serine/threonine kinase containing two N-terminal LIM domains in tandem, a PDZ domain and a C-terminal catalytic domain. LIMK1 is involved in modulation of actin cytoskeleton through inactivating phosphorylation of the ADF (actin depolymerization factor) family protein cofilin. Recent studies have shown that LIMK1 is upregulated in breast and prostate cancer cells and tissues, promotes metastasis in animals and induces acquisition of an invasive phenotype when ectopically expressed in benign prostate epithelial (BPH) cells. Furthermore, overexpression of LIMK1 was associated with altered sub cellular localization of the membrane type 1 matrix metalloprotease (MT1-MMP). Matrix metalloproteases (MMPs) are a family of zinc dependant proteolytic enzymes that hydrolyze extra cellular matrix and cell surface molecules. A number of MMPs including MMP-2, MMP-9 and their activator MT1-MMP are over expressed in a variety of cancers including prostate cancer. The abundant expression of these enzymes contributes to changes in the tumor microenvironment, which facilitate degradation of the surrounding collagen matrix and migration of cells through the matrix defects. In this study, we show that MMPs are involved in LIMK1 induced invasion of otherwise non-invasive BPH cells. We also show that (a) the kinase activity of LIMK is not essential for the invasive behavior of the cells and (b) the absence of LIM domains significantly retards cell invasion. We have established transfected sub lines of BPH cells stably expressing 1) constitutively active LIMK1 (BPHLCA), 2) kinase dead LIMK1 (BPHLKD) and 3) only the kinase domain of LIMK1 (BPHLK) for our study. In vitro invasion assays revealed that LIMK1 induced invasion was inhibited by the MMP specific inhibitor, GM6001, and that cells expressing kinase-dead LIMK1 were equally invasive. Furthermore, BPH cells expressing LIMK1 mutants expressed higher amounts of MMP-2 and MMP-9. Substrate zymography revealed increased concentration of secreted MMP-2 and MMP-9 in the media of BPHLCA and BPHLK cells respectively compared to BPHV (vector control) cells. Quantitative RT-PCR also showed a ~10 fold increase in the steady state concentration of MMP-2 in BPHLCA cells compared to the control BPHLV cells. Expression of active LIMK1 stimulated cell-surface expression of MT1-MMP in BPHLCA cells as determined by flow cytometry. A modest increase in expression of MT1-MMP was noted in BPHLKD cells compared to BPHLK and BPHV cells. Immunoflourescence analysis indicated differential localization of MT1-MMP and LIMK1 in BPH cells expressing different mutants of LIMK1. Co-localization of LIMK1 and MT1-MMP in the plasma membrane and in the perinuclear region was also evident in these cells. Furthermore, here we provide evidence that suggests a functional role for phosphorylated (activated) LIMK1/2 (p-LIMK1/2) during mitosis through its association with γ-tubulin. Immunoflourescence analysis showed distinct co-localization of γ -tubulin and p-LIMK1/2 in the centrosomes during mitosis from early prophase to the beginning of telophase. No association was seen in the interphase or in late telophase. Phospho-LIMK1/2 was co-precipitated in immunoprecipitates of γ -tubulin using an anti- γ -tubulin antibody suggesting a physical association between these proteins in a complex. This finding reveals a novel role of LIMK1 in the mitotic process. In summary, our data suggests that MMPs are involved in LIMK1 induced invasion of prostate epithelial cells, and that this effect is mediated through altered expression and activation of specific MMPs. Furthermore, LIMK1 induced invasion is dependant on the presence of LIM domains more than the kinase activity. Finally, we show that phosphorylated LIMK1 and LIMK2 are involved in the mitotic process in a stage specific manner through its association with the centrosomal protein γ -tubulin. Because LIMK1 promotes invasion in vitro, regulates expression of MMPs, and is involved in mitotic processes, it is an attractive drug target for prostate cancer therapy.

The inevitable progression of advanced prostate cancer to castration resistance, and ultimately to lethal metastatic disease, depends on primary or acquired resistance to conventional androgen-deprivation therapy (ADT) and accumulated resistance mechanisms to evade androgen receptor (AR) suppression. Whereas the canonical androgen/AR signaling axis maintains prostate cell growth, differentiation and survival, in prostate cancer cells, AR adaptations that arise in response to ADT are not singular, but diverse, and include gene amplification, mutation and even complete loss of receptor expression. Collectively, each of these AR adaptations contributes to a complex, heterogenous, ADT-resistant tumor that culminates in prostate tumor cells transitioning from epithelial to mesenchymal states (EMT) and the development of metastatic castration-resistant prostate cancer (mCRPC). Here, we examined prostate cancer cell lines that model common CRPC subtypes, each with different AR composition, and focused on novel regulators of tumor progression, the Bromodomain and ExtraTerminal (BET – BRD2, BRD3 and BRD4) family of proteins, to test the hypothesis that each BET family member regulates EMT and underlying characteristics such as cell motility and invasiveness. We systematically manipulated the BET proteins and found that BRD4 regulates cell migration and invasion across all models of CRPC, regardless of aggressiveness and AR status, whereas BRD2 and BRD3 only regulate cell migration and invasion in less aggressive models that retain AR expression or signaling. We determined that BRD4’s contribution to this process occurs through the transcriptional regulation of AHNAK, SNAI1 and SNAI2, which are EMT genes linked to promotion of metastasis in a diverse set of cancers. Furthermore, treatment of CRPC cell lines with low doses of MZ1, a small-molecule, BRD4-selective degrader, inhibits EMT and metastatic potential. Overall, these results reveal a novel, BRD4-regulated EMT gene signature that may be targetable to treat metastatic castration-resistant prostate cancer.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13517号 / 論医博第2267号 / 新制||医||1061(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 遊佐 宏介, 教授 戸井 雅和, 教授 小川 誠司 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Bakgrund: Prostatacancer är den näst vanligaste cancersjukdomen hos män. Sexuell dysfunktion är en vanlig komplikation efter prostatacancerbehandling som drabbar den sexuella hälsan. Flertalet män har frågor angående sexuell hälsa och sjuksköterskan bör därmed agera utifrån ett personcentrerat förhållningssätt. Syfte: Att belysa den sexuella hälsan bland män efter behandling av prostatacancer. Metod: Allmän litteraturstudie tillämpades för kandidatuppsatsen. Tio vetenskapliga artiklar användes i studien. Artiklarna granskades flera gånger för att sedan jämföras och analyseras genom innehållsanalys. Resultat: De framkom tre kategorier och åtta underkategorier. Den första kategorin som identifierades var ”Sexuell dysfunktion och efterföljande konsekvenser”. Den andra var ”Mannens intima relationer förändrades”. Den sista kategorin som uppkom var ”Mannens behov av stöd och information”. Sexuell dysfunktion kan resultera i att män upplever en förändrad självbild och påverkat psykosocialt mående. Mannens intima relationer kan förändras. Män kan därför uppleva behov av stöd och information från sjuksköterskan. Konklusion: Den förändrade sexuella hälsan hos mannen kan ge komplexa efterföljder som kan påverka mannens psykosociala mående och relationer. Vidare forskning om mäns sexuella hälsa kan behövas för att sjuksköterskan ska kunna ge tillräcklig information och stöd efter prostatacancerbehandling. / Background: Prostate cancer is the second most common cancer disease among men. Sexual dysfunction is a common post treatment complication that affects sexual health. The majority of men have questions about sexual health and nurses should act based on person-centred approach. Purpose: To enlighten the sexual health among men post prostate cancer treatment. Method: A general literature review was applied to the bachelor´s thesis. Ten scientific articles were used during the study. The articles were reviewed several times and compared and analysed through content analysis. Results: Three categories and eight subcategories emerged. The first identified category was “Sexual Dysfunction and following consequences”. The second was “The man’s changed intimate relationships”. The last category was “The man’s need for support and information”. Sexual dysfunction can result in that men experience a change in self-image and affected psychosocial well-being. The man’s intimate relationship can change. Men may therefore need support and information from nurses. Conclusion: A change in men’s sexual health can have complex consequences that affects the man’s psychosocial well-being and relationships. Further research about men’s sexual health may be needed for the nurse to be able to provide sufficient information and support post prostate cancer treatment.

Bakgrund: Prostatacancer är den vanligaste cancerformen som drabbar män i Sverige. Prostatakörteln är lokaliserad strax under urinblåsan och vid prostatacancer växer en tumör i prostatakörteln. Inkontinens, erektil dysfunktion och värmevallningar är vanligt förekommande biverkningar från behandlingen av prostatacancern. Syfte: Syftet med litteraturstudien var att beskriva mäns upplevelser av att leva med prostatacancer efter påbörjad behandling. Metod: Studien genomfördes som en allmän litteraturstudie och från två olika databaser framkom nio resultatartiklar. Resultatartiklarna granskades, bearbetades och sammanställdes till fem teman. Resultat: De teman som framkom var: brist på information, upplevelse av stöd, känslomässigt lidande, sexuell dysfunktion och behandlingspåverkan. Resultatet visade att män med prostatacancer upplevde brist på information från vårdpersonal samt att stöd från familj, vänner och vårdpersonal var en viktig del i hanteringen av prostatacancern. Männen upplevde både fysiskt samt psykiskt lidande. Konklusion: Män med prostatacancer är i behov av adekvat information och stöd. Sjuksköterskan bör även öka sin kunskap om mäns upplevelser av att leva med prostatacancer för att ha mer insikt vid tillämpning av personcentrerad omvårdnad. / Background: Prostate cancer is the most common form of cancer that afflicts men in Sweden. The prostate gland is located below the bladder and in case of prostate cancer a tumor grows inside the prostate gland. Incontinence, erectile dysfunction and hot flashes are common side effects from prostate cancer treatment. Aim: The aim of the literature study was to describe men's experiences of living with prostate cancer after initiated cancer treatment. Method: The study was implemented as a general literature study and nine result articles emerged from two different databases. The resulting articles were reviewed, processed and compiled into five themes. Result: Five main themes were identified: lack of information, experience of support, emotional suffering, sexual dysfunction and treatment impact. It appeared from the results that men with prostate cancer experienced lack of information from healthcare providers and that support from family, friends and healthcare providers was an important part of managing prostate cancer. The men experienced both physical and psychological suffering. Conclusion: Men with prostate cancer are in need of adequate information and support. Nurses should also increase their knowledge of men’s experiences of living with prostate cancer in order to have more insight when applying a person-centered care.

Liquid biopsy and next-generation sequencing of cell-free DNA (cfDNA) in cancer patients’ plasma offer a minimally-invasive solution to detect tumor cell genomic information to aid real-time clinical decision-making. Reliability and sensitivity in the detection of genomic alterations is crucial for patient management and it is particularly relevant in the context of targeted therapies. However, biological and technical factors, such as low cfDNA tumor fraction and sequencing errors, affect the correct interpretation of genomic data limiting the utility of non-invasive cfDNA-based tumor profiling. To address these issues, we designed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation of patients’ tumor. The framework also implements ABEMUS, an ad-hoc computational procedure we specifically designed for cfDNA samples to accurately detect somatic point mutations that could emerge under treatment pressure and as drug resistance mechanism. When applied on serial plasma samples from three patients receiving PARP inhibition harboring DNA repair gene aberrations, PCF_SELECT demonstrated high sensitivity in detecting BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be incongruent with protein losses. As a step towards a more sensitive detection of tumor features in circulation of cancer patients, we next hypothesized that recent WGS-based approaches exploiting cfDNA fragments characteristics could be extrapolated for targeted sequencing data and that gene-region specific measures could improve detection metrics. Preliminary results suggest an increased sensitivity compared to copy-number-based methods supporting the integration at no extra cost in our targeted assay. Overall, this work is relevant to the context of precision oncology. It provides an innovative platform for the management of cancer patients, delivering detailed patient-specific molecular information which could be applied to guide treatment and improve clinical outcomes.

Bakgrund: Radikal prostatektomi är en onkologisk botande behandlingsmetod mot lokaliserad prostatacancer. Komplikationer till ingreppet är bland annat sexuell dysfunktion vilket påverkar patienterna negativt. Syfte: Syftet var att belysa patienters upplevelser av sexuell dysfunktion efter radikal prostatektomi. Metod: Studien genomfördes som en allmän litteraturstudie med induktiv ansats där 11 resultatartiklar ur databaserna PubMed, CINAHL och PsycINFO inkluderades. För att besvara syftet på studien bearbetades artiklarnas innehåll och sammanställdes i flera steg. Resultat:Sexuell dysfunktion var något nästan alla patienter upplevde. Den sexuella dysfunktionen orsakade negativ självkänsla och upplevelse av minskad maskulinitet. Patienter upplevde att den sexuella dysfunktionen blev värre i samband med brist på information om komplikationer postoperativt. Patienter kunde i viss utsträckning få sexuell återhämtning med hjälp av medicinering mot erektil dysfunktion. En god partnerrelation var ett viktigt emotionellt stöd postoperativt. Sexuell dysfunktion påverkade relationer både positivt och negativt. Konklusion: Patienterna påverkades negativt av sexuell dysfunktion. Information om komplikationerna var viktigt för att öka återhämtning och minska lidande. Studien var värdefull för att sjuksköterskor ska ha möjligheten att bättre vårda patienter som genomgått en radikal prostatektomi. / Background: Radical prostatectomy is an oncological curative treatment method for localized prostate cancer. Complications of the procedure include sexual dysfunction, which negatively affects patients. Objective:The aim was to illuminate patients' experiences of sexual dysfunction after radical prostatectomy. Method: The study was conducted as a literature review with an inductive approach, including 11 research articles from the databases PubMed, CINAHL, and PsycINFO. To answer the purpose of the study, the content of the articles was processed and compiled in several steps. Results: Almost all patients experienced sexual dysfunction which caused them to experience negative self-esteem and self- perceived masculinity. Patients described that the sexual dysfunction worsened in connection with the lack of information about postoperative complications. Patients could to some extent achieve sexual recovery with medication for erectile dysfunction. A good partner relationship was an important emotional support postoperatively. Sexual dysfunction affected relationshipsboth positively and negatively. Conclusion: Patients was negatively affected by sexual dysfunction. Information about complications is crucial to enhance recovery and reduce suffering. The study was valuable for nurses to provide better care for patients who has underwent radical prostatectomy.