(UroToday.com) The 2025 European Association of Urology (EAU) Annual Congress held in Madrid, Spain was host to plenary session on organ-sparing paradigms in kidney and bladder cancer. Drs. Phillip Pierorazio, Nina Harke, Shankar Siva, and Dmitry Enikeev discussed various treatment approaches for the management of a 3 cm small renal mass.
Dr. Sara Vellamo Tornberg began with a case presentation of a 75-year-old male, BMI 26 kg/m2, with a good performance status, and the following past medical history:
- Moderate aortic valve stenosis
- Coronary artery disease (stent placed in 2004)
- Atrial fibrillation on warfarin
- GFR: 55 ml/min
- pT3N1M0 hypopharyngeal epidermoid carcinoma in 2018, treated with chemoradiation (no evidence of disease recurrence)
He was found to have a solid 3 cm right lower pole exophytic lesion (RENAL nephrometry score: 6p). This lesion was biopsied and found to be ccRCC, grade 2–3.
What are the treatment options for this patient?
- Active surveillance
- Operative treatment
- Radiotherapy
- Ablation therapy
Dr. Phillip Pierorazio argued in favor of active surveillance in this setting. He noted that there are several important considerations when weighing treatment options for patients with small renal masses:
- Patient and family preferences
- Ability to tolerate surgery
- Renal function
- Patient life expectancy
- Tumor biology
Starting off with the biologic rationale for active surveillance for small renal masses, he highlighted that no tumor <3 cm ‘has ever metastasized’. As seen in the bar graph and table below, the 3-year probability of metastasis was 0% for lesions <3 cm in size, based on the Mayo Clinic series.1 This risk increases to:
- 3-5 cm lesions: ~2%
- 5-7 cm lesions: 6-7%
- ≥7 cm: ~20%
Dr. Pierorazio noted that these lesions tend to be ‘genetically cold’ with a limited number of mutations that underlies their indolent nature, with cT1a clear cell lesions ‘born’ decades before a small renal mass presents itself.
It is important that we consider competing risks of mortality from other causes, when considering treatment for small renal masses. Psutka et al. have previously demonstrated that patients with small renal masses who opt for active surveillance are significantly more likely to die of other causes, as illustrated in the bottom right graph:2
Long-term outcomes data from the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry has demonstrated that patients undergoing active surveillance are unlikely to die of their renal cell carcinoma.
These small renal masses appear to have slow growth patterns, with a median growth rate of 0.11 cm/year median growth rate.
Overall, 70% of patients with small renal masses remain free of intervention at 10 years, with patients harboring small renal masses >3 cm significantly more likely undergo an intervention, compared to those with smaller lesions.
In addition to tumor size, other factors that influence the odds of delayed intervention include tumor growth rates >0.5 cm/year and patient preference (e.g., increasing anxiety over time).
While patient preference/anxiety is an important factor driving delayed intervention, Dr. Pierorazio noted that the mental/emotional quality of life improves over time for all patients with small renal masses opting for active surveillance.
What are some important clinical considerations for small renal masses? For non-growing small renal masses (i.e., stable size), the rate of metastatic development is 0%.
The average annual rate of small renal masses tumor growth varies by the underlying histology. Finelli et al. have demonstrated that clear cell lesions frow faster than papillary type 1 lesions (0.25 and 0.02 cm/year on average).3
It is important to note that although growth rate predicts delayed intervention, it does not predict oncologic outcomes. In other words, faster growing small renal masses are not necessarily associated with worse outcomes, compared to slower growing lesions.
Dr. Pierorazio concluded his presentation with the following summary slide on size triggers for enrollment of patients on active surveillance protocols versus immediate/delayed intervention.
Next, Dr. Nina Harke advocated for surgical intervention in this setting, particularly for partial nephrectomy, as opposed to a radical nephrectomy. She noted that the current EAU guidelines recommend offering partial nephrectomy to patients with T1 tumors and those with T2 tumors with solitary kidneys and/or chronic kidney disease, if technically feasible. A radical nephrectomy should be offered to patients with T2 tumors not amenable to a partial nephrectomy. The AUA similarly provides guidance on this matter noting that a radical nephrectomy is preferred if all of the following criteria are met:
- High tumor complexity and partial nephrectomy would be challenging, even in experienced hands
- No pre-existing CKD
- Normal contralateral kidney and new baseline eGFR would be likely >45 ml/min
Does this rationale apply to elderly patients as well? Data from the RESURGE project of partial versus radical nephrectomy in very elderly patients has demonstrated that partial nephrectomy, compared to a radical nephrectomy, is associated with higher complication rates, namely intra-operative transfusions (16 versus 9) and post-operative complications (34 versus 27) with no significant difference in overall mortality rates. However, patients undergoing a partial nephrectomy had lower rates of de novo CKD (HR: 0.28, p<0.01) and worsening of eGFR to <45 ml/min (HR: 0.53, p<0.01) or <30 ml/min (HR: 0.42, p<0.01).4
What about an open versus robotic approach to a partial nephrectomy in frail patients? Patients undergoing a robotic partial nephrectomy had lower overall and major complication rates, less blood transfusions, shorter hospital length of stay, and lower cardiac and pulmonary complication rates.
The ‘trifecta’ goal with partial nephrectomies is to achieve a warm ischemia time <25 minutes, obtain negative surgical margins, and avoid any complications. In a matched analysis of 880 patients, the ‘trifecta’ rate with partial nephrectomies was similar for patients <70 (70.2%) versus ≥70 years (72%). The odds of a ‘trifecta’ were higher for females (OR: 1.24), smaller tumor sizes, and less complex lesions.6
Dr. Harke concluded by re-iterating that surgery is the ideal approach for this patient, specifically a robotic partial nephrectomy.
Next, Dr. Shankar Siva argued the case for stereotactic body radiotherapy (SBRT) for the patients in the case presentation. He noted that this patient has several adverse features that discourage us from offering surgical interventions:
- Surveillance is reasonable – but is the growth rate concerning?
- Elderly (75 years)
- On anticoagulation (warfarin) for aortic valve stenosis
- Prior radiotherapy exposure
- Renal impairment (eGFR: 55 ml/min)
SBRT (or SABR) may be an alternative option in this setting that ‘may tick all the boxes’. SBRT avoids general anesthesia, is technically feasible for perihilar and large tumors, and is a non-invasive approach.
Prospective trials of SBRT are summarized in the table below. Dr. Siva highlighted that the median tumor size of SBRT-treated lesions in these trials ranged from 2.3 to 8.7 cm. The local control rates, particularly for more recent trials, ranged between 90–100%. The mean eGFR loss with SBRT appears to be ~10 ml/min.
A recent systematic review and meta-analysis comparing the efficacy and safety of ablative therapies for the management of primary, localized RCC demonstrated that at 5 years, the local control rate for SBRT (95%) was slightly superior to that of radiofrequency ablation (92%), microwave ablation (86%), and cryoablation (90%). Notably, SBRT-treated lesions (~4 cm) were larger than those treated with other ablative techniques (~3 cm).7
How does the mean decline in eGFR with SBRT compare to that of other modalities? While superior to that observed with radical nephrectomy (-8.6 versus -21.8 ml/min), it is comparable, if not inferior, to that observed with ablation (-5.1 ml/min) and partial nephrectomies (-5.5 ml/min).
Notably SBRT is associated with significantly fewer grade 3–5 adverse events, compared to ablation and partial nephrectomy:
Dr. Siva concluded by noting that if choosing treatment, SBRT may be the best choice due to its non-invasive nature, high efficacy, and low adverse event profile that has been assessed in multiple clinical trials.
Finally, Dr. Dmitry Enikeev advocated for ablation in this setting. He noted that current guidelines, including those of the EAU, AUA, ASCO, and NCCN, all consider partial nephrectomy equivalent to ablation for cT1a lesions.
With the presence of numerous ablation techniques, what is the best approach? Irrespective of the ablation modality, he noted that CT guidance is key given its:
- Safety in solitary kidneys
- Offers fast and precise anatomy assessment
- May be combined with ultrasound at the surgeon’s discretion
- May be substituted with MRI (with similar accuracy)
Ablation techniques have been shown to have similar efficacy outcomes, compared to partial nephrectomy,8 with lower morbidity rates (hospital stay: shorter by 1.76 days; blood loss lower by ~100 ml; lower complication rates: OR=0.62, p=0.004).9
What about thermal ablation versus active surveillance? A systematic review and meta-analysis demonstrated that patients undergoing thermal ablation had superior 3-year cancer-specific survival (RR: 1.55, p=0.02) and 3- and 7-year overall survival rates (RR: 1.85, p=0.03), compared to patients undergoing active surveillance.
What about ablation for cT1b tumors? A similar trend is observed with similar 5-year local recurrence-free survival rates for patients with cT1b tumors undergoing partial nephrectomy (92%) versus ablation (93%; p=0.6).10
Dr. Enikeev concluded as follows:
- For T1a renal masses, ablation is the method of choice in elderly patients or those with comorbidities and is a viable treatment option for all patient groups.
- For T1b renal masses, ablation is a promising treatment modality with a 5-year overall survival comparable to that of partial nephrectomy
Presented by:
- Phillip Pierorazio, MD, Chief of Urology, Penn Presbyterian Hospital, The University of Pennsylvania, Philadelphia, PA
- Nina Harke, MD, FEBU, Clinic for Urology, Hannover Medical School, Hannover, Niedersachsen, Germany
- Shankar Siva, PhD, MBBS, FRANZCR, Radiation Oncologist, Professor of Medicine, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia
- Dmitry Enikeev, MD, Professor of Urology, Vienna Medical University, Vienna, Austria
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the European Association of Urology (EAU) 2025 Annual Meeting, Madrid, Spain, Fri, Mar 21 – Mon, Mar 24, 2025.
References:
- Thompson RH, Hill JR, Babayev Y, et al. Metastatic renal cell carcinoma risk according to tumor size. J Urol. 2009; 182:41–5.
- Psutka SP, Gulati R, Jewett MAS, et al. A Clinical Decision Aid to Support Personalized Treatment Selection for Patients with Clinical T1 Renal Masses: Results from a Multi-institutional Competing-risks Analysis. Eur Urol. 2022; 81(6): 576-85.
- Finelli A, Cheung DC, Al-Matar A, et al. Small Renal Mass Surveillance: Histology-specific Growth Rates in a Biopsy-characterized Cohort. Eur Urol. 2020; 78(3): 460-7.
- Mir MC, Pavan N, Capitanio U, et al. Partial versus radical nephrectomy in very elderly patients: a propensity score analysis of surgical, functional and oncologic outcomes (RESURGE project). World J Urol. 2020; 38(1): 151-8.
- Rosiello G, Palumbo C, Deuker M, et al. Partial nephrectomy in frail patients: Benefits of robot-assisted surgery. Surg Oncol. 2021; 101588.
- Sharma G, Shah M, Ahluwalia P, et al. Perioperative outcomes following robot-assisted partial nephrectomy for complex renal masses: A Vattikuti Collective Quality Initiative database study. Indian J Urol. 2022; 38(4): 288-95.
- Huan RS, Chow R, Benour A, et al. Comparative efficacy and safety of ablative therapies in the management of primary localised renal cell carcinoma: a systematic review and meta-analysis. Lancet Oncol. 2025; 26(3): 387-98.
- Thompson RH, Atwell T, Schmit G, et al. Comparison of partial nephrectomy and percutaneous ablation for cT1 renal masses. Eur Urol. 2015; 67(2): 252-9.
- Gao H, Zhou L, Zhang J, et al. Comparative efficacy of cryoablation versus robot-assisted partial nephrectomy in the treatment of cT1 renal tumors: a systematic review and meta-analysis. BMC Cancer. 2024; 24(1): 1150.
- Andrews JR, Atwell T, Schmit G, et al. Oncologic Outcomes Following Partial Nephrectomy and Percutaneous Ablation for cT1 Renal Masses. Eur Urol. 2019; 76(2): 244-51.