During my clinical placements, I began to notice that some patients did not fit neatly into the scenarios we learned about in lectures. One patient in particular had a raised PSA and several comorbidities, including obesity. What stood out was not just the discussion about prostate cancer risk, but how much his weight seemed to influence the decisions being made; whether imaging would be accurate, how safe surgery would be, and what treatment options were realistic.
Until then, I had mainly thought about obesity as a risk factor that increases the likelihood of developing certain cancers, including renal cell carcinoma (RCC) and prostate cancer (PCa). However, seeing patients in clinic made me realise that its implications are much broader. It appeared to affect not just whether a disease develops, but how it is investigated and managed in practice.
This prompted me to reflect on how well our current approaches to care take this into account. Many of the guidelines and pathways we learn are based on an “average” patient, but in reality, a significant number of patients do not fit that profile. As a result, I began to wonder whether this might impact how effectively we diagnose and treat urological cancers in patients with obesity.
In this article, I aim to explore how obesity might influence different stages of the cancer pathway, from detection through to treatment. More broadly, it reflects a shift in how I am starting to think about medicine; not just in terms of diseases, but in terms of the patients we treat and the practical challenges that come with their care.
Pathophysiology
To understand how obesity may influence the clinical management of urological cancers, it is useful to first consider the underlying biology. RCC and PCa are commonly used examples, although the relationship with obesity is not completely straightforward.
For example, a large study in The Lancet showed that increasing BMI is associated with a higher risk of renal cancer, with about a 4–5% increase in risk for every 1-point rise in BMI [1]. In contrast, the relationship with PCa is more complex. The same study reported an overall inverse association between BMI and prostate cancer risk, likely reflecting a pooled analysis across all disease stages [1]. However, emerging evidence suggests that obesity may be more strongly associated with advanced prostate cancer rather than localised disease [2]. Overall, the literature appears to support a meaningful association between obesity and urological cancers, although the exact nature of this relationship varies by tumour type and stage.
Two main biological mechanisms are often discussed: chronic low-grade inflammation and changes in insulin and IGF-1 signalling.
Chronic inflammation
Obesity is characterised by a chronic, low-grade inflammatory state. Excess adipose tissue leads to elevated levels of inflammatory cytokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), both of which have been linked to the development of RCC and PCa [3,4].
Several studies discuss immune cells called myeloid-derived suppressor cells (MDSCs), which seem to play a role in suppressing the body’s anti-tumour response. MDSCs are known to accumulate in inflammatory states and have thus been proposed as a mechanism by which obesity may promote oncologic risk. In some experimental models, these cells release cytokines that reduce T cell activity and may promote tumour growth [5]. In prostate cancer specifically, MDSCs have been shown to produce interleukin-23 (IL-23), which might reactivate androgen receptor signalling and contribute to treatment resistance [4,6]. There is also some evidence of similar pathways in RCC, particularly involving chemokines like CCL2 [7,8].
Although these findings suggest that obesity-induced inflammation may promote tumour development and immune evasion, much of this evidence is derived from preclinical or early translational studies. Therefore, its direct clinical relevance remains to be fully established and warrants caution about how directly this applies to patients.
Hyperinsulinaemia and IGF-1
Another mechanism involves metabolic changes seen in obesity, particularly increased insulin levels and higher circulating IGF-1. These have been linked to cancer progression, especially in more advanced prostate cancer. While early prostate cancer is usually androgen-dependent, it appears that residual androgen-independent cells can continue to grow through alternative pathways, including IGF-1 signalling [2,3]. Although this pathway is complex, its downstream effect on cell adhesion and migration may promote tumour growth and spread by affecting cell adhesion and migration [2].
The obesity paradox
One of the more intriguing aspects of this topic is the so-called “obesity paradox.” Despite obesity being linked with increased cancer risk, several studies suggest that patients with higher BMI may actually have better survival in RCC and advanced prostate cancer [9–11]. The reasons for this remain unclear. Proposed explanations include differences in tumour biology, such as altered metabolic and fatty acid gene expression in tumours arising in obesogenic environments, as well as earlier detection due to increased healthcare contact or screening patterns [9,10]. It is also possible that BMI itself is an imperfect measure of metabolic health, which may confound these observations.
Overall, this makes the relationship between obesity and cancer feel quite complex. Rather than having a single effect, obesity seems to influence different parts of the cancer pathway in different ways. As a medical student, this has made me realise how important it is to look beyond simple associations and think more carefully about how these factors actually affect patients in practice.
What the current system might be missing
When considering how obesity affects outcomes in urological cancers, detection is a critical starting point. If cancers are not identified early, then differences in management and outcomes may already be influenced from the start of diagnosis.
PSA screening
One issue I came across is the relationship between BMI and prostate-specific antigen (PSA) levels. There is evidence that PSA levels tend to be lower in patients with higher BMI, possibly due to a haemodilution effect from increased plasma volume [12]. This could mean that PSA is less sensitive in detecting prostate cancer in patients with obesity and may partly explain lower biopsy rates in this group [13].
Although PSA is not used in isolation, it still plays an important role in deciding who goes on to have further investigations such as imaging or biopsy. Current screening approaches in the UK and Ireland take into account factors such as age, lower urinary tract symptoms, ethnicity and family history – but BMI is not included [14,15].
This raises important questions about how this may affect patients. For example, if a man with obesity has a PSA that falls below the usual threshold, could his risk be underestimated? It raises the question of whether standard PSA thresholds are appropriate for all patients, or whether adjustments based on BMI might improve detection.
Imaging challenges
Obesity can also make imaging more difficult. Increased tissue thickness and fat attenuation can reduce image quality, potentially affecting how accurately tumours are assessed. In renal cancer, for example, CT scans may be less reliable in estimating tumour size in patients with higher BMI [16]. This could have practical implications, particularly in cases where decisions depend on tumour size, such as choosing between surveillance and intervention. It may also mean that clinicians need to rely more on other imaging modalities, such as MRI, which are more costly and not always as readily available.
Surgical treatment: higher risk?
When I started thinking about how obesity affects surgical management, it became clear that many of the challenges are very practical. In patients with obesity, operations can be technically more difficult, particularly due to issues with access and positioning. Excess adipose tissue, especially in the pelvis, can make it harder to visualise structures and may prolong operative time [17,18].
This seems to be seen across a range of procedures, including robotic prostatectomy and open nephrectomy [19,20]. Longer operating times are often linked with higher risks of complications and slower recovery, which may also increase overall healthcare costs [17].
Notably, despite these recognised challenges, standard workflows do not always appear to change significantly. Surgeons clearly adapt in practice, but these adaptations don’t seem to be formally built into planning systems. Operating lists, for example, may not always account for longer case durations or more complex setup in patients with obesity. Access to specialised equipment can also vary between centres and technical adjustments – such as port placement – often depend on individual surgeon experience rather than standardised approaches [19,21].
Obesity adds important complexity to anaesthetic management in urologic surgery, which may be underappreciated from a surgical perspective. Intubation can be more difficult, and increased abdominal mass can impair ventilation by displacing the diaphragm and increasing intrathoracic pressures. This becomes even more relevant in procedures that require Trendelenburg positioning and pneumoperitoneum, which are common in urological surgery. These factors can impair microcirculatory perfusion and strain cardiopulmonary function, potentially compromising pulmonary gas exchange and cardiac output [22,23].
Putting this together, it seems that obesity adds multiple layers of complexity – not just surgically, but across the whole perioperative pathway. As a student, this made me question whether our current systems are fully designed to account for this. Given the increasing prevelance of obesity among urologic cancer patients in modern populations, is it enough to rely on individual clinician adaptation, or should these challenges be more formally built into how we plan and deliver surgical care [24]?
What can the future look like?
Thinking about all of this, it seems likely that as urological cancer care evolves, our clinical systems will also need to adapt to reflect the growing prevalence of obesity. If a large proportion of patients fall outside the “average” profile assumed in many guidelines, approaches to screening, imaging and surgical planning need to evolve alongside this.
From what I have read, there are several areas where potential approaches could be considered. For example, adjusting PSA thresholds in patients with higher BMI might help address the issue of haemodilution. Imaging pathways may need to become more flexible, particularly where technical limitations affect diagnostic accuracy. In surgery, more structured preoperative planning could help anticipate some of the additional challenges that arise in patients with obesity.
Representation in research is another important issue. If patients with obesity are underrepresented in clinical trials, then the evidence base we rely on may not fully reflect the populations we see in practice. Improving this could help ensure that future guidelines are more applicable to real-world patients.
At the same time, the emergence of newer anti-obesity medications, such as Semaglutide, Tirzepatide, and Retatrutide, may begin to change the landscape. These treatments have shown significant weight loss effects and are becoming more widely used in clinical practice [25–27]. It raises an interesting question as to whether some of the challenges discussed in this article might become less prominent over time if obesity becomes more manageable at a population level.
However, it seems unlikely that obesity will disappear completely in the near future. Factors such as access to treatment, long-term adherence, cost, and variation in response mean that many patients will continue to present with obesity [28]. For now, it remains important that clinical systems are designed to accommodate these patients, rather than assuming the problem will resolve itself.
As I continue through my medical training, I’ve started to think about medicine not just in terms of diseases, but in terms of the systems that deliver care. Writing this has highlighted how factors like obesity don’t just influence risk, they shape how care is delivered and experienced. It also makes me wonder where relatively small changes in these systems could lead to meaningful improvements for patients.
TAKE HOME MESSAGES
-
Obesity influences the entire urological cancer pathway, from risk and detection through to treatment and outcomes.
-
PSA-based screening may underestimate cancer risk in patients with obesity, and current approaches do not routinely account for this.
-
Diagnostic imaging can be less accurate in patients with higher BMI, which may affect staging and clinical decision-making.
-
Surgical and anaesthetic complexity is increased in patients with obesity, yet these challenges are not always fully reflected in standard workflows.
References
1. Bhaskaran K, Douglas I, Forbes H, et al. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults. Lancet 2014;384(9945):755–65.
2. Siech C, Rutz J, Maxeiner S, et al. Insulin-like Growth Factor-1 Influences Prostate Cancer Cell Growth and Invasion through an Integrin α3, α5, αV, and β1 Dependent Mechanism. Cancers (Basel) 2022;14(2):363.
3. Papavasileiou G, Tsilingiris D, Spyrou N, et al. Obesity and main urologic cancers: Current systematic evidence, novel biological mechanisms, perspectives and challenges. Semin Cancer Biol 2023;91:70–98.
4. de Bono JS, Guo C, Gurel B, et al. Prostate carcinogenesis: inflammatory storms. Nat Rev Cancer 2020;20(8):455–69.
5. Ostrand-Rosenberg S. Myeloid derived-suppressor cells: their role in cancer and obesity. Curr Opin Immunol 2018;51:68–75.
6. Calcinotto A, Spataro C, Zagato E, et al. IL-23 secreted by myeloid cells drives castration-resistant prostate cancer. Nature 2018;559(7714):363–9.
7. Hale M, Itani F, Buchta CM, et al. Obesity Triggers Enhanced MDSC Accumulation in Murine Renal Tumors via Elevated Local Production of CCL2. PLoS One 2015;10(3):e0118784.
8. Lukesová S, Kopecký O, Vroblová V, et al. Determination of angiogenic factors in serum by protein array in patients with renal cell carcinoma. Folia Biol (Praha) 2008;54(4):134–40.
9. Hakimi AA, Furberg H, Zabor EC, et al. An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. J Natl Cancer Inst 2013;105(24):1862–70.
10. Kim LH, Doan P, He Y, et al. A Systematic Review and Meta-Analysis of the Significance of Body Mass Index on Kidney Cancer Outcomes. J Urol 2021;205(2):346–55.
11. Martini A, Shah QN, Waingankar N, et al. The obesity paradox in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 2022;25(3):472–8.
12. Choi H, Park J, Cho B, et al. The illusion of prostate‐specific antigen decline in patients with metabolic syndrome and insulin resistance. BJU Int 2011;108(11):1756–61.
13. Parekh N, Lin Y, Dipaola RS, et al. Obesity and prostate cancer detection: insights from three national surveys. Am J Med 2010;123(9):829–35.
14. National Cancer Control Programme. HSE National Clinical Guideline: Diagnosis And Staging Of Patients With Prostate Cancer (National Clinical Guideline). HSE National Clinical Guideline 2025.
https://www2.healthservice.hse.ie/organisation/
national-pppgs/national-clinical-guideline-diagnosis
-and-staging-of-patients-with-prostate-cancer/
15. National Institute for Health and Care Excellence. Prostate cancer: diagnosis and management. NICE 2021.
https://www.nice.org.uk/guidance/ng131
16. Son Y, Quiring ME, Dalton RM, et al. Renal mass imaging modalities: does body mass index (BMI) matter? Int Urol Nephrol 2024;56(8):2483–7.
17. Bensalah K, Raman JD, Bagrodia A, et al. Does obesity impact the costs of partial and radical nephrectomy? J Urol 2008;179(5):1714–8.
18. Khater N, Morris AG, Vanvalkenburg DM, et al. Clinical Considerations and Outcomes of Robotic Urologic Surgery in Obese Patients. Turk J Anaesthesiol Reanim 2024;52(2):39–48.
19. Wiltz AL, Shikanov S, Eggener SE, et al. Robotic radical prostatectomy in overweight and obese patients: oncological and validated-functional outcomes. Urology 2009;73(2):316–22.
20. Sperling CD, Xia L, Berger IB, et al. Obesity and 30-Day Outcomes Following Minimally Invasive Nephrectomy. Urology 2018;121:104–11.
21. Huynh LM, Ahlering TE. Robot-Assisted Radical Prostatectomy: A Step-by-Step Guide. J Endourol 2018;32(S1):S28–32.
22. Tharp WG, Murphy S, Breidenstein MW, et al. Body Habitus and Dynamic Surgical Conditions Independently Impair Pulmonary Mechanics during Robotic-assisted Laparoscopic Surgery. Anesthesiology 2020;133(4):750–63.
23. Atkinson TM, Giraud GD, Togioka BM, et al. Cardiovascular and Ventilatory Consequences of Laparoscopic Surgery. Circulation 2017;135(7):700–10.
24. Deol ES, Lehner KS, Fadel AE, et al. Impact of obesity on prostatectomy outcomes: Insights from a large prospectively maintained cohort. Urol Oncol 2025;43(5):334.e7–334.e15.
25. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021;384(11):989–1002.
26. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387(3):205–16.
27. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity – A Phase 2 Trial. N Engl J Med 2023;389(6):514–26.
28. Scragg J, Koutoukidis DA, Dirksen C, et al. The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity. Med 2025;6(9):100805.
[All links last accessed April 2026]
Declaration of competing interests: None declared.
