Oligometastatic Disease in Prostate Cancer: Advances in Diagnosis and Treatment

Prostate cancer (PC) is the second most common cancer in men and the fifth leading cause of death in men worldwide in 2012 [1]. Oligometastatic disease is defined as the presence of five or fewer metastatic or recurrent lesions that could be treated by local therapy to achieve long‐term survival or cure [2]. Androgen deprivation therapy is currently the accepted treatment of metastatic PC. However, the identification of oligometastatic disease in PC with the improvements in diagnostic imaging has lead to early treatment of these isolated metastases showing some benefit [3]. In this chapter, we aim to discuss the newer modalities used in the identification of oligometastatic disease in PC and the advances in treatment

The role of localised prostate cancer treatment in renal transplant patients: a systematic review

Objective To systematically review and critically appraise all treatment options for localised prostate cancer in renal transplant candidates and recipients. Method A systematic review was conducted adhering to PRISMA guidelines. Searches were performed in the Cochrane Library, Embase, Medline, the Transplant Library and Trip database for studies published up to September 2022. Risk of bias was assessed with the Cochrane Risk of Bias in Non-Randomised Studies of Interventions for non-randomised studies tool. Results A total of 60 studies were identified describing 525 patients. The majority of studies were either retrospective non-randomised comparative or case series/reports of poor quality. The vast majority of studies were focussed on prostate cancer after renal transplantation. Overall, 410 (78%) patients underwent surgery, 93 (18%) patients underwent radiation therapy or brachytherapy, one patient underwent focal therapy (high-intensity frequency ultrasound) and 21 patients were placed on active surveillance. The mean age was 61 years old, the mean PSA level at diagnosis was 9.6 ng/mL and the mean follow-up time was 31 months. The majority of patients had low-risk disease with 261 patients having Gleason 6 prostate cancer (50%), followed by 220 Gleason 7 patients (42%). All prostate cancer mortality cases were in high-risk prostate cancer (≥Gleason 8). The cancer-specific survival results were similar between surgery and radiotherapy at 1 and 3 years. Conclusion Localised prostate cancer treatment in renal transplant patients should be risk stratified. Surgery and radiation treatment for localised prostate cancer in renal transplant patients appear equally efficacious. Given the limitations of this study, future research should concentrate on developing a multicentre RCT with long-term registry follow-up

Kidney Tumor Detection using Attention based U-Net

The advancement of deep learning techniques has provoked the potential of using Medical Image Analysis (MIA) for disease detection and prediction in numerous ways. This has been mostly useful in identifying tumours and abnormalities in many organs of the human body. Particularly in kidney diseases, the treatment options such as surgery have largely benefitted by the ability to detect tumours in early stages, thereby shifting towards more efficient methods including conservative nephron procedures. Therefore, to enable the early detection of kidney tumours, we propose a convolutional neural network based U-Net architecture which is able to detect tumours using an attention mechanism. The proposed architecture was evaluated using KiTS19 Challenge dataset that includes a collection of multi-phase CT imaging, segmentation masks, and comprehensive clinical outcomes for 300 patients who underwent nephrectomy for kidney tumours. The outcomes demonstrate the ability of the proposed architecture to distinguish images with tumours in the kidney and support early tumour detection

Incidence of Bladder Cancer in Sri Lanka: Analysis of the Cancer Registry Data and Review of the Incidence of Bladder Cancer in the South Asian Population

PurposeTo investigate the incidence of bladder cancer (BC) in Sri Lanka and to compare risk factors and outcomes with those of other South Asian nations and South Asian migrants to the United Kingdom (UK) and the United States (US).Materials and MethodsThe incidence of BC in Sri Lanka was examined by using two separate cancer registry databases over a 5-year period. Smoking rates were compiled by using a population-based survey from 2001 to 2009 and the relative risk was calculated by using published data.ResultsA total of 637 new cases of BC were diagnosed over the 5-year period. Sri Lankan BC incidence increased from 1985 but remained low (1.36 and 0.3 per 100,000 in males and females) and was similar to the incidence in other South Asian countries. The incidence was lower, however, than in migrant populations in the US and the UK. In densely populated districts of Sri Lanka, these rates almost doubled. Urothelial carcinoma accounted for 72%. The prevalence of male smokers in Sri Lanka was 39%, whereas Pakistan had higher smoking rates with a 6-fold increase in BC.ConclusionsSri Lankan BC incidence was low, similar to other South Asian countries (apart from Pakistan), but the actual incidence is likely higher than the cancer registry rates. Smoking is likely to be the main risk factor for BC. Possible under-reporting in rural areas could account for the low rates of BC in Sri Lanka. Any genetic or environmental protective effects of BC in South Asians seem to be lost on migration to the UK or the US and with higher levels of smoking, as seen in Pakistan

Survival outcomes of younger men (< 55 years) undergoing radical prostatectomy

Background: The aim of the paper is to investigate the outcomes of patients younger than 55 years in Victoria, Australia undergoing radical prostatectomy (RP) for prostate cancer. Materials and methods: Data on all men undergoing RP in Victoria between January 1, 2004 and December 31, 2014 were obtained from the Victorian Cancer Registry. Tumor characteristics including Gleason grade, stage of disease (based on final pathology specimen), and cause of death were also obtained. Statistical analysis was performed using Chi-square test, Cox proportional hazards method, and Kaplan-Meier analysis. Results: A total of 14,686 men underwent RP during the defined period. Of these men 109 were aged 35–44 years and 1,998 were aged 45–54 years. Men aged 35–44 years and 45–54 years were compared against men aged 55–74 years. The majority of men between the ages of 35 years and 44 years, and 45 years and 54 years had higher rates of Gleason ≤ 7 disease compared with men aged between 55 years and 74 years (92.7% vs. 86.8% vs. 79.3%; P < 0.01) and ≤ T2 disease (82.6% vs. 75.6% vs. 49.9%; P < 0.01) but similar median prostate-specific antigen values. On a multivariate analysis adjusting for Gleason score, T stage, and prostate-specific antigen, men aged 45–54 years and 55–64 years had 67% and 46% increase in overall survival, respectively, compared to men aged 65–74 years; but these differences were not seen in the 35–44 year age group. There were no differences in prostate cancer specific deaths between the groups. The 5- and 10-year overall survival outcomes were both higher for men aged 45–54 years compared to mean aged 55–74 years (97.9% vs. 95.9% and 94.9% vs. 85.3). Conclusion: Men aged 45–54 years undergoing RP had better overall survival compared to men aged 55–74 years, but these effects were not seen in men aged 35–44 years. There were no differences in prostate cancer specific survival in these groups

The role of hypoxia inducible factor 1 alpha (HIF1α) in prostate cancer

© 2016 Dr. Weranja Kalana Bodhisiri RanasingheProstate cancer (PC) is one of the most prevalent cancers in men. Although many PCs are indolent, a significant proportion will metastasize and develop resistance to therapy. Contemporary screening tests lack the finesse to accurately differentiate aggressive PCs from indolent tumours, potentially leading to over-diagnosis and over-treatment. While cellular hypoxia often plays an integral role in carcinogenesis and tumour progression, this connection has been difficult to demonstrate in PC. However, a downstream marker of hypoxia, Hypoxia inducible factor 1α (HIF1α), which is a transcription factor that protects cells against noxious stimuli, is frequently over expressed in PC. Therefore, the role of HIF1α in PC was investigated in this thesis. The Castrate resistant PC (CRPC)-like human PC cell lines PC3 and DU145 were found to over-express HIF1α protein compared to an androgen-sensitive cell line LNCaP under normoxic conditions. Using HIF1α 5’UTR-luciferase constructs in PC3 cells, further experiments revealed that increased translation of HIF1α mRNA regulated by a 70bp GC-rich, secondary structure in the 5’UTR of the HIF1α promoter may be responsible for normoxic HIF1α overexpression. Cell proliferation assays revealed that PC3 cells over-expressing HIF1α were more resistant to destruction by cytotoxic agents (H2O2 and 5-fluorouracil) than androgen-dependent LNCaP cells. Reduction of HIF1α expression in PC3 cells using RNA interference decreased both the resistance towards cytotoxic agents and cell migration. Conversely, in the androgen-dependent LNCaP cells overexpression of HIF1α increased the resistance to cytotoxic agents. One hundred prostate tumours were then immune-stained for HIF1α and outcomes measured. On multivariate analysis HIF1α was an independent risk factor for progression to metastatic PC (Hazard ratio (HR) 9.8, p = 0.017) and development of CRPC (HR 10.0, p = 0.021) in patients on androgen-deprivation therapy (ADT). Notably the tumours that did not express HIF1α did not metastasise or develop CRPC. Next, the effects of non-specific HIF1α inhibitors (digoxin, metformin and angiotensin-2 receptor blockers) were investigated in ninety-eight patients who had continuous ADT as first line therapy and developed CRPC. The median CRPC-free survival was longer in men using HIF1α inhibitors compared to those not on inhibitors (6.7 yrs vs. 2.7yrs, p=0.01) and there was a 71% reduction in the risk of developing CRPC (p=0.02) and an 81% reduction in the risk of developing metastases (p=0.02) after adjustment for Gleason score, age and PSA. Finally, the effects of metformin were investigated in 2055 men treated for PC with external beam radiotherapy. Surprisingly, metformin did not result in any improvement in time to biochemical failure, time to metastases or overall survival in men undergoing radiotherapy, but there was an 1.5 fold increase in PC-specific deaths (p<0.05) in men on metformin who received ADT when adjusted for cancer risk and co-morbidities. In conclusion, the results presented in this thesis indicate that HIF1α is a promising marker in PC, which may be used for early identification of cancers that potentially will progress to metastases and develop resistance to ADT. HIF1α is likely to contribute to metastasis and chemo-resistance of CRPC, targeted reduction of HIF1α may improve outcomes of aggressive PC

The decision-making role of the patient in localised prostate cancer treatment

Our objective was to review the current literature on patient participation and decision-making in the treatment selection process for localised prostate cancer, and to evaluate capacity for improvement. Methods: 42 articles from our literature search were deemed eligible and relevant for review. We reviewed studies on all facets of the treatment decision-making process with most number of articles (16) on treatment preferences. Results: The majority of the patients prefer an active or collaborative role in decision-making. Patients are seeking information from a myriad of sources but the recommendation from their treating physician is often the most influential on the final decision. Radical prostatectomy is more likely to be selected in patients who view a cure for cancer as being of the utmost importance and radiation therapy is preferred in patients who are concerned about treatment side effects. Conclusion: Currently no ideal tool exists to assist patients in making informed treatment decisions that also takes into account patients’ values and preferences. We encourage collaborative partnership in a multidisciplinary setting to optimise this process and individualised risk-based decision-making tools may provide a better pathway to assist patients reach decisions

The decision-making role of the patient in localised prostate cancer treatment

Our objective was to review the current literature on patient participation and decision-making in the treatment selection process for localised prostate cancer, and to evaluate capacity for improvement. Methods: 42 articles from our literature search were deemed eligible and relevant for review. We reviewed studies on all facets of the treatment decision-making process with most number of articles (16) on treatment preferences. Results: The majority of the patients prefer an active or collaborative role in decision-making. Patients are seeking information from a myriad of sources but the recommendation from their treating physician is often the most influential on the final decision. Radical prostatectomy is more likely to be selected in patients who view a cure for cancer as being of the utmost importance and radiation therapy is preferred in patients who are concerned about treatment side effects. Conclusion: Currently no ideal tool exists to assist patients in making informed treatment decisions that also takes into account patients’ values and preferences. We encourage collaborative partnership in a multidisciplinary setting to optimise this process and individualised risk-based decision-making tools may provide a better pathway to assist patients reach decisions