Real-life Data on First- and Second-Line Treatment of Metastatic Castration-Resistant Prostate Cancer With Abiraterone, Enzalutamide and Cabazitaxel - A multicentric Study From Portugal.

INTRODUCTION AND OBJECTIVES: New drugs for metastatic castrate resistant prostate cancer (mCRPC) were approved, first in the pos-docetaxel and then in the pre-docetaxel setting. We aim to assess the real daily practice benefit of abiraterone (Abi), enzalutamide (Enz) and cabazitaxel (Cab) in patients with mCRPC, compare it with RCT results and compare Abi vs Enz. MATERIALS AND METHODS: We retrospectively collected the data of all consecutive mCRPC patients treated with Abi, Enz or Cab in the six major oncological hospitals in the north of Portugal until December 2020. RESULTS: A total of 470 treatments pre-docetaxel (163 Abi and 307 Enz) and 373 pos-docetaxel (160 Abi, 148 Enz and 59 Cab) were included, with median follow-up time of 35 months. Mean age was 73.1, 84.4% had ECOG status < 2, ISUP grade was ≥ 4 in 59% and 28.0% had oligometastatic disease. In first line, for Abi and for Enz respectively, the proportion of patients with PSA reduction > 50% was 64.4% and 80.4% (P < .001), the mean duration of treatment (DT) was 10 and 14 months (P = .037) and the median overall survival (OS) was 25 months and 30 months (P = .17). In second line the results for Abi, Enz and Cab were respectively: proportion of patients with PSA reduction > 50% was 40.4%, 57.4% and 24.6% (p for Abi vs Enz=0.004); DT was 7, 8, and 3 months (p for Abi vs Enz = 0.27); OS was 17, 22 and 10 months (p for Abi vs. Enz = 0,07). CONCLUSION: These drugs have good efficacy in real-world evidence, similar to those reported in randomized clinical trials, with the expected exception of lower OS due to the inclusion of a broader sample of patients. Our results add to the evidence that Enz might have better efficacy in this setting compared with Abi.

Prognostic impact of variant histology in bladder cancer: Would early and aggressive treatment shift the paradigm?

INTRODUCTION: Bladder cancer (BC) is an increasingly frequent malignancy worldwide. Several variant histologies (VH) have been described in BC with a distinct clinical behavior. OBJECTIVES: This study aims to assess the prognostic impact of VH in BC, comparing its outcomes to pure urothelial carcinoma PUC in both non-muscle invasive (NMIBC) and muscle-invasive (MIBC) settings. METHODS: We included patients with primary BC, comparing those with VH with those with PUC, with an age and sex-matched proportion of 1:3, considering stage at diagnosis, recurrence-free, progression-free, and overall survival (OS). A total of 616 patients were included in the study, (460 UC and 151 VH). RESULTS: After first TURBT, MIBC was present in 99 (64.1%) of patients with VH, and 95 (20.6%) with UC (p<0.001). Concerning NMIBC, we observed higher rates of progression to MIBC amid patients with VH (p=0.009). Nodal involvement (p=0.020) and metastatic disease (p<0.001) were significantly higher within the VH group. A higher OS was observed among patients with NMIBC of PUC (p<0.001). There were no statistically significant differences of metastasis-free survival and OS between VH and UC groups within the MIBC setting. CONCLUSION: We confirmed that VH presents a more aggressive clinical course compared to PUC. An earlier radical treatment within the NMIBC setting could increase the oncological outcomes of the VH patients.

Association between sociodemographic and clinical features, health behaviors, and health literacy of patients with prostate cancer and prostate cancer prognostic stage.

Patient characteristics may influence access and acceptance of Prostate Specific Antigen test, and therefore, the timing of prostate cancer (PCa) diagnosis. A group of 361 patients from a cohort (n = 451) diagnosed with PCa in 2018-2020 at the Portuguese Institute of Oncology of Porto was evaluated before treatment, using a structured interview, the Medical Term Recognition Test, and the EORTC Quality of Life Questionnaire QLQ-PR25. PCa prognostic stages (I, II, III, IV) were attributed according to the American Joint Committee on Cancer eighth edition. Multinomial logistic regression was used to compute the odds ratio and 95% confidence interval (OR [95% CI]), considering PCa stage II, the most frequent, as reference. Older age (OR = 4.21 [2.24-7.93]), living outside the Porto Metropolitan Area while having low income (OR = 6.25 [1.53-25.62]), and erectile dysfunction (OR = 2.22 [0.99-4.99]) were associated with stage III, while urination during the night (OR = 3.02 [1.42-6.41]) was associated with stage IV. Urine leakage was less frequent in stage III (OR = 0.23 [0.08-0.68]), and living with a partner (OR = 0.41 [0.19-0.88]) and family history of cancer (OR = 0.25 [0.07-0.86]) in stage IV. Health literacy was not associated with PCa stage but lower education was less frequent in stage I (OR = 0.27 [0.11-0.69]). Patient sociodemographic and clinical characteristics should be considered as targets to improve PCa early detection and prognosis.

Prostate cancer treatment in Portugal: a nationwide analysis.

Different treatment options exist for localized prostate cancer. Treatments performed in high-volume hospitals are associated with better results. Our objective was to describe time trends in prostate cancer treatments in Portugal and case volume per hospital. We used the national database of diagnosis-related group of the Portuguese Central Administration of the Health System to describe the number of radical prostatectomy (RP), brachytherapy (BT) and external radiotherapy (eRT) treatments performed in all National Health System hospitals. There was a rapid increase in the annual number of RP until 2006 and then a deceleration; BT treatments augmented significantly until 2011. The utilization of eRT also increased, surpassing RP after 2010. From the 46 hospitals performing RP, only eight had a case-volume > 50 treatments/year, and from the nine hospitals performing BT, only four accomplished > 15 treatments/year. In the 11 hospitals with eRT, nine performed > 50/year. Regarding RP, there was negative correlation between the hospital volume and length of stay (r = - 0.303; p = 0.041). In the Portuguese National Health Service there was a steep increase in the number of prostate cancer treatments, and there is an ample margin for concentration of RP and BT treatments, for improvement of the hospitals case volume.

Anxiety and Depression in Patients with Prostate Cancer, at Cancer Diagnosis and after a One-Year Follow-Up.

Prostate cancer (PCa) is the most prevalent among men, and psychological symptoms may affect many patients. This study aims to describe the prevalence of probable anxiety and depression before PCa treatments and after one year and to identify sociodemographic and clinical factors associated with these outcomes. Between February 2018 and March 2020, 292 patients recently diagnosed with PCa were recruited at the Instituto Português de Oncologia-Porto. The Hospital Anxiety and Depression Scale (HADS) was used to define probable anxiety and depression (cutoff = 11). The prevalence of probable anxiety remained stable from baseline to one year (7.8% vs. 8.5%, p = 0.866) while there was an increase in probable depression (3.1% vs. 6.8%, p = 0.012). After one year, probable depression persisted in 55.6% of patients with probable depression at baseline and 47.8% of those with probable anxiety at the first assessment had normal anxiety scores. At baseline, anxiety was more frequent among dwellers in rural areas (adjusted odds ratio-aOR, 95%CI: 2.80, 0.91-8.58) and less frequent in patients with body mass index 25-29.9 kg/m2 (aOR, 95%CI: 0.33, 0.12-0.91) compared to 18.5-24.9 Kg/m2, while those living alone had higher odds of depression (aOR, 95%CI: 6.35, 1.43-28.30). The frequency of anxiety and depression fluctuated during the course of treatment. Monitoring these symptoms would identify the most affected patients, contributing for a better use of mental health services.

Prevalence of Cognitive Impairment before Prostate Cancer Treatment.

Cognitive impairment is common among patients with different types of cancer, even before cancer treatment, but no data were reported among patients with prostate cancer (PCa), who may be at high risk due to advanced age. This study aims to estimate the prevalence of cognitive impairment before PCa treatment. Between February 2018 and April 2021, the NEON-PC cohort recruited 605 patients with PCa proposed for treatment at the Portuguese Institute of Oncology of Porto. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. Participants with a MoCA < 1.5 standard deviations (SD) of age- and education-specific normative values were considered to have probable cognitive impairment (PCI) and were referred for a comprehensive neuropsychological assessment. Data from the population-based cohort EPIPorto (n = 351 men aged ≥40 years, evaluated in 2013−2015) were used for comparison. The prevalence of PCI was 17.4% in EPIPorto and 14.7% in NEON-PC (age- and education-adjusted odds ratio: 0.82, 95%CI: 0.58,1.18). Neuropsychological assessment was performed in 63 patients with PCa: 54.0% had cognitive impairment. These results suggest that the impact of PCa on cognitive performance could be negligible in the short term, contrary to what other studies have reported regarding other types of cancer.

Updating and Integrating Core Outcome Sets for Localised, Locally Advanced, Metastatic, and Nonmetastatic Castration-resistant Prostate Cancer: An Update from the PIONEER Consortium.

CONTEXT: Harmonisation of outcome reporting and definitions for clinical trials and routine patient records can enable health care systems to provide more efficient outcome-driven and patient-centred interventions. We report on the work of the PIONEER Consortium in this context for prostate cancer (PCa). OBJECTIVE: To update and integrate existing core outcome sets (COS) for PCa for the different stages of the disease, assess their applicability, and develop standardised definitions of prioritised outcomes. EVIDENCE ACQUISITION: We followed a four-stage process involving: (1) systematic reviews; (2) qualitative interviews; (3) expert group meetings to agree standardised terminologies; and (4) recommendations for the most appropriate definitions of clinician-reported outcomes. EVIDENCE SYNTHESIS: Following four systematic reviews, a multinational interview study, and expert group consensus meetings, we defined the most clinically suitable definitions for (1) COS for localised and locally advanced PCa and (2) COS for metastatic and nonmetastatic castration-resistant PCa. No new outcomes were identified in our COS for localised and locally advanced PCa. For our COS for metastatic and nonmetastatic castration-resistant PCa, nine new core outcomes were identified. CONCLUSIONS: These are the first COS for PCa for which the definitions of prioritised outcomes have been surveyed in a systematic, transparent, and replicable way. This is also the first time that outcome definitions across all prostate cancer COS have been agreed on by a multidisciplinary expert group and recommended for use in research and clinical practice. To limit heterogeneity across research, these COS should be recommended for future effectiveness trials, systematic reviews, guidelines and clinical practice of localised and metastatic PCa. PATIENT SUMMARY: Patient outcomes after treatment for prostate cancer (PCa) are difficult to compare because of variability. To allow better use of data from patients with PCa, the PIONEER Consortium has standardised and recommended outcomes (and their definitions) that should be collected as a minimum in all future studies.

Renal Cell Carcinoma with Venous Thrombus: Should Surgery Be Offered When Metastasis Is Present at Diagnosis?

INTRODUCTION: Renal cell carcinoma (RCC) reveals a tendency towards venous invasion in its advanced stages, making clinical management challenging. Survival may be improved following surgery, but is less clear if it applies to patients with metastatic disease at diagnosis. MATERIALS AND METHODS: Review of clinical files of patients submitted to surgery for RCC at our institution. RESULTS: Twenty-one patients underwent radical nephrectomy and thrombectomy from 2000 to 2017, with a median follow-up of 25 months. Eighteen (85.7%) men and 3 (14.3%) women, with median age of 63 at the time of diagnosis, were included. The thrombus was in the renal vein in 10 (47.6%) patients and had extension to inferior vena cava (IVC) in 11 (52.4%). The level of involvement in IVC was grade II in 4 (19%) cases, grade III in 4 (19%) cases and grade IV in 3 (14.4%) cases. Surgery was successful in all but 1 patient. Ten patients died during the follow-up (47.6%), resulting in a 5-year overall survival of 34.8%. When considering the metastatic population at diagnosis, the overall survival at 5 years was 45.7%. CONCLUSION: Radical nephrectomy with removal of the venous thrombus remains the preferential treatment for patients with RCC with venous thrombus, even if they have metastatic disease at diagnosis.

Sex differences in the association between a previous cancer diagnosis and the use of medication.

We aimed to quantify the association between a previous cancer diagnosis and medication use, depicting possible sex differences. We analysed data from a representative sample of the Portuguese adult population (n=32 610), which was collected through face-to-face interviews, using a structured questionnaire. The effect of a previous diagnosis of cancer was quantified through prevalence ratios (PR), adjusted for age, education and region of residence. Cancer survivors (CS) reported higher use of prescribed medication, with greater adjusted PR among men (1.25 vs. 1.13, P for interaction=0.001). Compared with the general population, male CS reported higher use of drugs for sleep problems, allergies and antibiotics, whereas female CS reported greater consumption of drugs for depression, anxiety, sleep problems and pain. This study contributes towards understanding sex disparities in the impact of cancer survival on medication use.

Incidence of second primary cancers in North Portugal-a population-based study.

PURPOSE: Longitudinal studies are needed to characterise the burden of second primary malignancies among cancer survivors. Therefore, we quantified the incidence rate and cumulative incidence of second primary cancers (SPC) and standardised incidence ratios (SIR) in a population-based cohort of subjects diagnosed with a first primary cancer (FPC). METHODS: We evaluated a cohort of cancer patients from the Portuguese North Region Cancer Registry (RORENO), with the first diagnosis in 2000-2003 (n = 39451), to estimate the incidence rate and cumulative incidence of SPC and standardised incidence ratios (SIR), for different periods of follow-up, up to 5 years; SPC were defined according to the International Association of Cancer Registries and the International Agency for Research on Cancer guidelines. RESULTS: The incidence rate of SPC was more than 5-fold higher in the first 2 months of follow-up than in the period between 2 months and 5 years (metachronous SPC), across which the incidence rates were relatively stable. Cancer survivors had an overall higher incidence rate of cancer than the general population (SIR = 1.31 (95 % confidence interval (CI), 1.25-1.38)), although that difference faded when only metachronous SPC were considered (SIR = 1.02 (95 % CI, 0.96-1.08)). Cancer incidence rates were higher among female lung FPC survivors and lower in prostate FPC cancer survivors than in the general population. The 5-year cumulative risk of developing a metachronous SPC was 3.0 % and reached nearly 5.0 % among patients with FPC associated with lower risk of death. CONCLUSIONS: Cancer survivors had higher incident rates of cancer that the general population, especially due to diagnoses in the first months following the FPC. Nevertheless, after this period SPC remain frequent events among cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: SPC constitute an important dimension of the burden of cancer survivorship, and this needs to be taken into account when defining strategies for surveillance, prevention and counselling.

Health status, use of healthcare, and socio-economic implications of cancer survivorship in Portugal: results from the Fourth National Health Survey.

PURPOSE: Understanding the morbidity and socio-economic implications of cancer survivorship is essential for a comprehensive management of oncological diseases. We compared cancer survivors (CS) with the general population regarding health status, use of healthcare resources and socio-economic condition. METHODS: We analyzed data from a representative sample of the Portuguese population aged ≥15 years (n = 35,229). We defined three groups of CS, according to the time since diagnosis and the latest cancer treatment: CS 1 diagnosis within 12 months of interview; CS 2 diagnosis more than 12 months before and treatment in the previous 12 months; CS 3 diagnosis and treatment more than 12 months before. These were compared with the general population, adjusting for differences in sex, age, and place of residence. RESULTS: The prevalence of CS was 2.2% (CS 1: 0.2%; CS 2: 0.9%, CS 3: 1.1%). Self-perceived health status was worse among CS and short-time incapacity more frequent among CS 1 and CS 2. Health expenses were higher in the early stages of survivorship. Lower household income and financial difficulties were more frequent in CS 1 and CS 3 men, respectively. CONCLUSION: This study confirmed the higher consumption of healthcare resources and worse financial situation among CS. IMPLICATIONS FOR CANCER SURVIVORS: Our study provides valuable information for understanding the global impact of cancer survivorship.

Evaluation of the frequency of and survival from second primary cancers in North Portugal: a population-based study.

A marked increase in cancer survival and in the frequency of second primary cancers (SPCs) has been observed in the latest decades, propelling the investigation of their burden at a population level. We aimed to quantify the proportion of SPCs among the incident cases in North Portugal and to describe their survival. We identified all SPCs (excluding skin nonmelanoma) registered by the North Region Cancer Registry (RORENO) from 2000 to 2003 according to the International Association of Cancer Registries and the International Agency for Research on Cancer guidelines. We classified tumors diagnosed more than 2 months after a first primary cancer (FPC) as metachronous. The observed survival was computed using vital status in December 2010. A total of 1607 SPCs (3.8% of all cancers) were registered (77.9% metachronous). The most frequent metachronous SPC topographies and the corresponding most frequent FPCs were of the colon (12.2%; FPC: prostate, breast, and stomach), lung (10.5%; FPC: bladder, stomach, and colon), and stomach (9.7%; FPC: prostate, breast, and bladder). The overall 5-year survival of individuals with metachronous SPCs was 47.4%; within the subgroups with higher (63.1%) and lower survival (31.1%), there were no significant differences across groups of FPCs with expectably different survival. The proportion of SPCs was that anticipated for a registry with approximately one decade of activity. The most common cancers in the general population were also frequent metachronous SPCs, whereas the most frequent FPCs were high incidence and survival cancers. The survival of metachronous SPCs did not vary with the survival expected for the FPCs.

Health-related behaviours in the EpiPorto study: cancer survivors versus participants with no cancer history.

Cancer survivors are at an increased risk of a second primary cancer, partly due to unhealthy behaviours. In a cohort of adults (recruitment: 1999-2003; follow-up - linkage with population-based cancer registry: up to 2009) we compared the baseline exposure to smoking, alcohol and dietary intake and physical activity between: cancer survivors (CS) - cancer diagnosis before baseline (n=53); no cancer (NC) participants - without cancer diagnosis at baseline or during follow-up (n=2261); latent cancer (LC) participants - without cancer diagnosis at baseline but diagnosed during follow-up (n=139). Age-, sex- and education-adjusted prevalences and means were computed, as applicable. The prevalence of current smoking was nearly 20% among CS and NC (approximately four cigarettes per day) and 30% in LC (seven cigarettes per day). LC had the highest average alcohol intake (25.5 g/day) and NC the lowest (17.0 g/day). The proportion of participants reporting sports practice was higher for CS (50%) than for NC or LC (approximately 33%). CS and NC had higher fruit/vegetable consumption than LC (4.2 and 4.4 vs. 3.8 servings per day). In a composite index on health behaviours (including smoking, physical activity and alcohol and fruit/vegetable intake) the highest and lowest scores were 1.74 for NC and 1.52 for LC respectively, whereas CS scored 1.63. The exposure to each risk factor appeared comparable in CS and NC, whereas LC tended to have unhealthier behaviours. This may be partially explained by the acquisition of healthier habits by CS after diagnosis, but there still remains scope for improvement, as revealed by the low scores observed for the joint exposure to the main risk factors.

TP53 codon 72 polymorphism in susceptibility, overall survival, and adjuvant therapy response of gliomas.

TP53 is a key tumor suppressor gene that encodes a transcriptional factor involved in several cellular mechanisms, including growth arrest, DNA repair, and induction of apoptosis. In addition to TP53 gene mutations, a common polymorphism, Arg72Pro, has been involved in the carcinogenesis process. The Pro72 variant has been associated with a slower induction of apoptosis and may influence the risk of cancer development. The role of Arg72Pro polymorphism in glioma susceptibility is poorly characterized. With the objective of analyzing the role of the TP53 Arg72Pro polymorphism in glioma risk, overall survival, and patient therapy response in a Portuguese population, we conducted a retrospective case-control study, including 171 patients with gliomas and 526 cancer-free individuals. The Arg72Pro genotype was assessed by the polymerase chain reaction-restriction fragment length polymorphism technique. No statistically significant differences were observed in the genotypic and allelic frequencies between glioma and control groups, and no statistically significant differences were observed with stratification of gliomas into distinct histological subtypes: astrocytic (n = 115), glioblastoma (n = 75), and oligodendroglial (n = 54) tumors. No significant association was observed between TP53 Arg72Pro and patient overall survival, but Kaplan-Meier analysis of glioma patients harboring the Pro72 allele showed a significantly longer survival with adjuvant therapy. In this first assessment of the role of TP53 Arg72Pro polymorphism in a large series of Portuguese glioma tumors, no association was observed with glioma susceptibility or overall survival, except for patients submitted to adjuvant therapy.