Navigating the labyrinth: A comprehensive approach to managing renal masses in young patients

Over the past two to three decades, there has been a dramatic shift in the epidemiology of renal cell carcinoma (RCC), with a rising incidence of asymptomatic incidental renal tumors and cysts detected at earlier clinical stages. This change in the presentation of RCC has been largely attributed to the advent and widespread availability of abdominal imaging, leading RCC to become the seventh most common among men and tenth among women. Not only are the majority of new RCC cases small renal masses (SRM, stage T1a), but they also tend to be found among older and more comorbid patients, which is the population most likely to undergo abdominal imaging. Naturally, this epidemiologic evolution has led to an abundance of studies and medical society guidelines focused on SRM in patients with a relatively limited life expectancy, resulting in the adoption of therapeutic strategies such as thermal ablation and active surveillance [1,2,3].

Another consequence of the rising detection of RCC has been the relatively dramatic increase in the incidence of RCC in young adults (<40 years old) from 0.4/100,000 person-years in 2000 to 0.8/100,000 person-years in 2016 [4]. While young patients constitute a minority of new cases of RCC, this small but enlarging demographic represents a unique challenge in management. Unlike asymptomatic SRM in an elderly population for which strategies have prioritized on minimizing risks and surgical trauma, the long-life expectancy of these young patients with SRM necessitates a uniquely different approach for management with a focus on optimizing quality of life and minimizing future morbidity.

The lack of literature focused on young adults exacerbates this challenge. Retrospective studies indicate that young adults are generally diagnosed at an early stage and exhibit superior cancer-specific survival rates. Nonetheless, a survival disparity between black and white RCC patients, particularly among younger patients and those with smaller tumors, and these racial disparities were largely explained by more prevalent comorbidities and social deprivation among blacks. This evidence was supported by a later publication that found that average cancer-specific survival rates were highest for non-Hispanic Whites and lowest for non-Hispanic African Americans in young adults.

While Metcalf et al. [5] argue that active surveillance is a viable initial strategy for younger patients—with no instances of metastatic risk during surveillance or recurrence post-delayed intervention—their study is confined to a median follow-up of just 4.9 years. Considering that the life expectancy of young patients is significantly longer, this poses a critical question: If the course of the disease will inevitably lead to surgical intervention, why initiate a period of active surveillance? Is active surveillance even a feasible option given that it implies potentially decades of imaging?

There are compelling arguments for why immediate surgery or short-term delayed surgery may offer advantages over long-term active surveillance. Subjecting young patients to active surveillance for a potentially malignant renal mass could have serious mental health consequences, such as increased anxiety and depression, affecting their overall quality of life. The psychological burden of living with a slow-growing tumor over a long-life expectancy should not be underestimated. Active surveillance as a long-term strategy can be emotionally taxing, perhaps more than undergoing definitive treatment. A systematic review has shown that active surveillance for SRMs, even when biopsy-proven as malignant, negatively impacts quality of life and psychological well-being [6].

While rapid growth of SRM often precedes metastatic progression—a change that can be quickly detected via regular imaging [7], it is equally valid that tumor growth rate remains an inconsistent indicator for distinguishing between benign and malignant behaviors. Both can demonstrate similar growth patterns or stay stable for extended periods. Thus, although clinicians may assure young patients of minimal metastatic risk, such assurances do little to alleviate the considerable burden of uncertainty these patients must carry.

Surgical approaches have evolved to become less invasive, significantly revolutionizing the landscape of renal interventions. Particularly for younger patients, minimally invasive surgical techniques present a lower risk of complications, making it an increasingly favorable treatment option. The gold standard for treating SRM remains partial nephrectomy. In most instances, percutaneous biopsy offers little utility, as it generally doesn't alter the treatment decision.

Active surveillance subject patients to repeated cross-sectional imaging and necessitates multiple follow-up visits, both of which have implications. These include exposing patients to avoidable radiation and imposing a significant financial burden on the healthcare system. Furthermore, the use of iodinated contrast media poses a risk for adverse reactions and renal function impairment.

Another point of discussion is the viability of thermal ablation as an alternative management for SRM in young patients. While methods such as radiofrequency and cryoablation are safe and less-than-surgery-invasive alternatives to treat SRM and, thus, favorable for certain patients who might not be suitable for surgical intervention, they might not be the best strategy for young patients for some reasons. First, by not removing the mass, thermal ablation parallels the disadvantages of active surveillance, including the negative psychological impact and the requirement for persistent long-term imaging follow-up. Second, the quality of pathological specimens obtained from a complete surgical resection provides the most comprehensive information about the nature of the SRM compared to a biopsy that could be nondiagnostic, indeterminate, or misestimate the tumor grade or other pathological features [8]. Further, the tissue obtained from the resection is valuable for genetic analysis for personalized oncology. Lastly, while the immediate oncological outcomes of thermal ablation might be comparable to surgery, the long-term oncological control remains unclear [9]. Given the relative novelty of these techniques, there is a need for long-term data to learn about the long-term oncological results of thermal ablation and compare them to the already-known excellent oncological outcomes offered by partial nephrectomy.

Partial nephrectomy is the only approach that offers a definitive treatment in all cases. Considering the previous discussion, we could argue that there is virtually no overtreatment for SRM in young patients. The benefits of removing a SRM in a young patient outweigh the risks of the surgery, regardless of the pathology result. The best alternative would probably be between an immediate resection and active surveillance and could be defined as a delayed treatment. Short-term delayed treatment could be used strategically as an opportunity for younger patients. This period could serve as a ‘teachable moment’, allowing physicians to adopt a holistic and multidisciplinary approach to health optimization. Within this window, patients who are generally more motivated can receive guidance on tackling various health-related issues—from smoking cessation and weight management to improved nutrition—before proceeding with surgical intervention. This preoperative phase thus presents an opportunity not only to prepare the patient for surgery but also to impact their overall health and quality of life positively.

It is paramount to suspect a genetic alteration in any patient with early onset of presentation, multifocal lesions, or a family history of RCC and refer them to genetic counseling and germline mutation testing. Five to 8% of RCCs are hereditary, and some studies have shown that young adults below the age of 46 may harbor 70% of all kidney cancers associated with hereditary diseases [10], and approximately 80% of all tumors found in young adults are malignant, and the rest comprise tumors of a benign origin. While universal screening for renal masses using ultrasound has not proven to be cost-effective on a population-wide scale, targeted screening for family members of young patients diagnosed with renal masses may warrant consideration. Screening could be a reasonable strategy in this narrow subpopulation. However, further research is essential to ascertain the efficacy of systematic screening in family members of young patients with renal masses.

In conclusion, managing SRMs in young adults requires an approach different from the conventional protocols often designed for older populations. The evidence suggests that while active surveillance may offer some advantages, it could place young patients under considerable psychological stress, making immediate or short-term delayed surgery a compelling alternative. Minimally invasive surgery has become a safe option with few complications, particularly for younger patients that provide a definitive treatment as opposed to repeated imaging and follow-ups that, in contrast, expose patients to unnecessary radiation and the healthcare system to a significant financial burden. Further, a brief delayed treatment offers a unique opportunity for comprehensive health optimization and should be considered part of a holistic treatment approach. Balancing clinical evidence with individual patient needs, concerns, and prospects remains challenging.