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REVIEW ARTICLE
Year : 2023 | Volume
: 34
| Issue : 3 | Page : 117-123
Small renal masses
Mandana Gholami1, Jihad Kaouk2, Homayoun Zargar3
1 College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, United Arab Emirates
2 Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
3 Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia
Correspondence Address:
Homayoun Zargar
University of Melbourne, Melbourne, Victoria
Australia
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/UROS.UROS_31_23
Small renal masses (SRM) are defined as contrast-enhancing solid masses detected on diagnostic imaging, with a size of less than or equal to 4cm, corresponding to renal cell carcinoma stage T1a. These tumours are mainly benign, with an indolent nature and rare metastatic potential. Given the size and nature of these tumours, there has been a significant evolution and in management modalities of these tumours. These range from conventional radical approaches such as radical nephrectomy, partial nephrectomy, to more conservative approaches such as active surveillance, and some novel emerging management strategies such as various thermal ablation techniques. The treatment decision depends on patient factors such as age and co-morbidity, and tumour factor on radiological imaging, such as tumour size, location, growth rate and biopsy result. In this review, we aim to provide the latest updates on approaching SRM and various management modalities.
Keywords: Partial nephrectomy, radical nephrectomy, renal mass, renal tumors, small renal masses, thermal ablation
Small renal masses (SRM) are defined as contrast-enhancing solid masses detected on abdominopelvic imaging, with a size of ≤4 cm. These tumors corresponds to renal cell carcinoma (RCC) stage T1a.[1] The incidental finding of these masses is growing, potentially owing it to the widespread use of cross-sectional imaging.[2]
Following the extirpation of these tumors, around 20% are found to be benign on histopathological analysis.[3] These benign tumors are mostly identified as oncocytoma, followed by angiomyolipoma and atypical cysts and various other rarely-occurring tumors of different pathologies.[3] Although the remaining 80% are malignant in nature, they are identified at a low grade and in the early clinical stages, opening doors to a variety of treatment options.[4] In addition, up to only about 6% of these tumors have exhibited metastasis at the time of diagnosis.[3] These tumors also exhibit excellent prognostic outcome following surgery, with 98%–100% 3-year metastases-free survival rate.[5]
Various factors guide the decision-making process for the management of SRMs. This includes patient-related factors such as the patient's age and comorbidities, and tumor-related factors such as tumor characteristics on imaging, history of growth, and biopsy results.[1] All the aforementioned factors need to be carefully evaluated, to yield a final safe and patient-centered decision.
Renal Mass BiopsyAlthough renal tumors are primarily detected on various imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound, they do not offer a definitive diagnosis. Moreover, CT scan, which is more often utilized than other imaging modalities, has been reported to provide a suboptimal sensitivity and specificity in diagnosing RCCs.[6] Therefore, renal mass biopsy (RMB) is necessary to assess the histological type of the tumor, as well as to guide treatment decisions of SRMs.[1] RMB can also serve as a significantly valuable tool aiding in decreasing unnecessary surgical intervention for benign tumors.[7]
The American Society of Clinical Oncology (ASCO) guidelines recommends considering a biopsy for every SRM identified and it is deemed necessary for patients undergoing ablation therapies before treatment. However, if a tumor is identified as predominantly cystic mass, SRMs originating in the collecting system, or a clinical suspicion for urothelial cancer, ASCO recommends against a biopsy.[1] According to the American Urological Association (AUA) guidelines, the most important indication for RMB is a mass suspicious of hematologic, metastatic, inflammatory, or infectious nature.[8] AUA advises against RMB for young or healthy patients who are unwilling to accept the uncertainties associated with RMB or older or frail patients who will be managed conservatively regardless of RMB findings.[8]
Moreover, the European Association of Urology (EAU) recommends RMB of solid masses (and not cystic masses) before ablative or systemic therapy, in the absence of previous pathology information.[9]
Active SurveillanceActive surveillance (AS) has emerged as an appealing alternate to radical approaches in SRM management. This surveillance strategy involves following up with patients at certain pre-determined intervals and monitoring tumor characteristics and behavior such as growth rate and/or metastasis using various imaging modalities. With such close supervision, patients could benefit from a potential decrease in over-treatment as well as the morbidity associated with more intense forms of treatment modalities, with an additional benefit of avoiding the financial burden of definitive treatment.[10]
Given the indolent nature of SRMs, along with its low rate of metastatic progression, AS proves as a safe management approach for majority of SRMs, while preserving patient's survival outcomes.[10],[11],[12] In fact, several prospective and retrospective studies assessing tumor-related behavior of patients on AS have reported cancer-specific mortality of as low as nearly 1%, with a similar rate of metastasis, if any.[11],[13],[14]
However, although these results are very promising, they should be interpreted with caution. These studies usually are conducted among a small number of patient population and usually do not have a long enough follow-up duration to confirm its oncological safety. To this date, no randomized trials exist to assess the feasibility, benefits, and superiority of AS.
Almost all major urological guidelines present a standard consensus regarding indications for AS.
Suitable candidates for AS are elderly patients with a life expectancy of equal to or less than 5 years, with significant comorbidities that declare them high-risk for surgery.[1]
Moreover, AUA meticulously delineates additional tumor-related factors for consideration by the treating physician. These factors include predominantly cystic tumors, with the size of <3 cm and <5mm growth per year. In addition, Bosniak 3/4 complex cystic renal mass falls into AS management criteria as well.[8]
Although the indication criteria are relatively consistent across all guidelines, there are slight discrepancies between guidelines with regard to surveillance intervals. ASCO recommends staging chest X-ray and axial abdominal imaging (or ultrasonography) every 3 months in the first year, twice in the second and third years, and yearly thereafter.[8] Moreover, EAU guidelines recommend CT, MRI, or US at 3 and 6 months, then every 6 months up to 3 years, and annually thereafter.[9] This recommendation agrees with the reported slow linear growth rate of approximately 1–5 mm/year of more than 40% of SRMs as well as low metastatic potential of SRMs in the first 3 years of initiation of AS protocols.[11] On the other hand, AUA guidelines follow a more static, yet more frequent approach, with cross-sectional imaging and/or US scan, conducted every 3–6 months.[8]
At any point during the surveillance period, patients can be further escalated to delayed intervention once the progression of the tumor has been noted.[11] Intervention is more commonly observed in the first 3 years of diagnosis, affirming the safety of AS over long term, with an added benefit of potentially reducing overtreatment. Several triggers have been identified by guidelines for progression to intervention. For instance, ASCO specifies that a tumor growth rate of 0.5 cm/year or a tumor exceeding 4 cm in size should be considered for intervention.[1] AUA recommends tumor-related factor triggers such as absolute size growth of >3cm, median growth rate in excess of 5 mm/year, or stage evolution, infiltrative appearance on imaging, or aggressive histology on RMB.[8]
Thermal AblationAs the management strategies for SRMs continue to evolve, the thermal ablation (TA) of SRMs has been gaining increasing attention, particularly due to its noninvasive nature. This method is either as a step up from AS or used as a safe alternative to invasive procedures amongst patients unfit for surgery.
TA encompasses various techniques, namely radiofrequency ablation (RFA), cryoablation (CA), and microwave ablation (MWA). The main guiding principle for all these techniques are either low or high temperatures.[15] Biopsy before any forms of TA is mandatory to confirm histopathological diagnosis as well as to aid in post-ablation follow-up surveillance.[8]
AUA and ASCO recommend this approach for tumors < 3 cm. TA in this patient group may be associated with less morbidity and better subsequent renal function.[1],[8],[16],[17],[18],[19] However, these guidelines do not specify which candidates are particularly suitable for each TA method.
In addition, EAU recommends TA for patients with a genetic predisposition to develop multiple tumors with recurrences after surgery, patients with bilateral tumors or a solitary kidney, and those at high risk of complete loss of renal function following partial nephrectomy (PN). EAU recommends against using this technique for SRMs located at the hilum or near the proximal ureter due to the high chance of injury to these structures. Nonetheless, given all the indications above, EAU does not recommend this procedure overall due to the lack of randomized control trials comparing TA with PN.[9]
The appealing minimally invasive nature of TA should not be overshadowed by the high likelihood of recurrence or persistence post ablation, where a repeat ablation is necessary to achieve equivalent end results to more invasive interventions.[8]
Moreover, several studies comparing outcome trends between TA and PN noted no difference in local recurrence or metastasis rate.[16] However, overall survival and recurrence-free survival seems to be more favorable with PN, possibly because of the older age of patients selected for TA.[20],[21]
Radiofrequency ablation
RFA is a high temperature-based ablative technique, whereby heat induces a primary cellular damage, followed by coagulative necrosis and vaporization. These outcomes are achieved at various temperatures, within seconds to minutes of initiation.[22]
RFA could be performed percutaneously through laparoscopy or under cross-sectional imaging guidance. This choice depends on the location of the tumor, with CT-guided RFA providing better access to posterior tumors and laparoscopy used for accessing tumors located elsewhere, as the laparoscopic instruments allow easier manipulation as well as deliver a 3-dimensional visualization of the anatomy.[22]
Satisfactory outcomes can be achieved within just a single session, and if ablation is successful, it can possibly eliminate the need of follow-up imaging.[23]
Recurrence in this setting is defined as “any discovery of enhancement of new or residual tumor at any point during follow-up with imaging on either CT or MRI anywhere in the originally ablated kidney.”[24] The incidence of recurrence increases with time, particularly if there is evidence of residual tissue because of incomplete ablation.[24],[25] Therefore, utmost care must be taken to meticulously ablate as much of the tumor as possible, while being cautious of not compromising the integrity of the surrounding anatomy.
Due to the minimally-invasive nature of the technique, RFA carries a lower risk of developing major complications. Majority of the reported complications fall into the Clavien–Dindo grade 1 category, with very low rates of major complications (Grade 3 or more) reported. Major complications include iatrogenic ureteric injury which subsequently causes urinary strictures or urine leaks, urinary retention, psoas necrosis, perinephric hematoma, and urosepsis.[24],[26],[27]
Cryoablation
CA technique induces cell death by cycles of freezing and thawing, using argon and helium gas. This method can also be performed percutaneously or laparoscopically, depending on tumor characteristics.[15]
CA offers acceptable recurrence-free survival and overall survival rates. However, the excellent results at the beginning seem to decline substantially over long-term follow-ups which would make it a less desirable option in the long run.[28],[29],[30] When compared to radiofrequency, CA seems to offer lower recurrence rates, but no other superiority of this method is observed with regards to long-term survival rates, its effect on renal function, or technique efficacy rate.[31]
As with RFA, complications observed with CA are mostly minor (Clavien–Dindo Grade 1-2), which can be successfully managed conservatively.[30]
Microwave ablation
MWA is an uprising novel approach within the spectrum of TA. In this instance, ablation is delivered using a 15-G microwave probe, under the guidance of ultrasound or CT-scan, to confirm correct positioning of the probe.[32],[33] With the availability of different microwave probes by different biomedical companies, this technique is highly manufacturer dependent, where they specifically dictate the duration and wattage of the microwave frequency to achieve the desired results.[32]
Compared to the previously mentioned techniques, there is a paucity of information on MWA of SRMs. The few studies present in the academic literature are of debatable strength, with insufficient patient population and short follow-up, where definite conclusions cannot be made regarding its safety, feasibility, and oncological outcomes.
One of the possible superior characteristics of this technique over RFA or CA is its shorter ablative time where higher temperatures are delivered, allowing coverage of larger ablation zones within a shorter period.[32],[34]
Moreover, it has been reported that MWA could potentially cause less complications compared to RFA and CA, where most of the complications are again Clavien–Dindo Grade I, rarely requiring intervention.[32],[33],[34] It is of significance to note that with MWA, operator experience plays a key role in avoiding untoward complications.[32],[35]
Nonetheless, this procedure does not seem to provide additional benefits as no evidence of the superiority of MWA exists with regards to efficacy rate, long-term survival data, complication rates, effect on kidney function or metastatic progression, and more solid data is required to assess these factors.[34]
Although recurrence rates are rarely reported in the small retrospective studies, follow-up with CT imaging is indicated to evaluate for recurrence or metastasis every 3 months for the first year and then annually thereafter.[32],[33],[34],[35]
Partial Nephrectomy/Nephron Sparing ApproachesOver the course of the past few decades, the management of SRM has greatly transitioned from radical nephrectomy (RN) to PN. Despite the emergence of various alternative non-surgical or minimally invasive options, all guidelines still recommend nephron-sparing approaches as standard of care for SRM. Nephron-sparing surgeries (NSS) provide excellent oncological outcomes, specifically favorable cancer-specific survival rate, but to be weighed against its potential surgical complications when compared to non-surgical interventions. The main goal of PN is the preservation of renal function. Therefore, it is postulated that this lower chance of chronic kidney disease (CKD) progression with PN could translate into a lower risk of cardiovascular morbidity and subsequently, overall mortality.[36]
AUA recommends prioritizing PN whenever a tumor is deemed feasible for intervention. In addition, it is recommended for solitary kidneys, bilateral masses, preexisting CKD, familial RCC, or proteinuria. This guideline suggests considering this procedure for young patients, patients with multifocal masses, or patients with comorbidities which could put them at risk of developing CKD.[8]
On the other hand, ASCO guideline recommends PN as a rather elective procedure, given the normal-functioning contralateral kidney.[1]
NSS is performed either open, laparoscopic, or through robot-assisted partial nephrectomies (RPN), which is being implemented extensively. However, the available body of literature provides debatable evidence as to which surgical technique offers the most successful and superior outcomes.
With regard to open PN, the only advantage it seems to offer is its shorter operative time, which when weighed against its cons such as increased blood loss and subsequent need for transfusions, rather seems an undesirable primary choice.[37],[38]
The “trifecta” outcome has been adopted as a gauge for assessing surgical quality in nephrectomies. This measurement tool is defined by three distinct surgical endpoints: achievement of negative surgical margins, absence of complications, and postoperative estimated glomerular filtration rate (eGFR) maintained at 90%.[37],[39]
Although no randomized control trial exists to confidently determine the superiority of the available PN methods, several studies have concluded the benefit of RPN in terms of shorter operative time, lower complications (specifically blood loss and the need for blood transfusion), and less positive margins.[39],[40] However, the perioperative eGFR changes seemed to be equivalent amongst both techniques, with no statistical significance observed.[39],[40] These outcomes have subsequently translated into a more desirable trifecta achievement in favor of RPN of up to seven times even when compared to laparoscopic PN (LPN).[39]
Several studies have endorsed the superiority of RPN over LPN but with conflicting results, where some report lower overall complications with RPN and lower positive margins, but with similar rates of blood loss, operation time, and eGFR changes.[41] On the other hand, a more recent Systematic Review and Meta-analysis (SRMA) which takes into account the R. E. N. A. L score of ≥7, which corresponds to the higher complexity of the tumor, have determined RPN to be valuable in terms of lower rate of conversion to radical surgery, shorter length of stay, less eGFR decline, and lower rate of CKD upstaging, when compared to LPN, especially in tumors with greater complexity.[42]
Radical NephrectomyWith the emergence of a plethora of alternative options, which are safer and associated with less comorbid profile, RN is moving towards obsoletion for the treatment of SRMs. This method is now only reserved for a scrupulous patient population who possess significantly challenging tumor complexity which is not amenable to PN, regardless of surgeon's skills and expertise, or undergoing PN might put them at risk of undesirable morbidity.[1]
In addition, AUA stringently delineates that the patient must not only meet the above criteria but must not have preexisting CKD or proteinuria, a contralateral normal functioning kidney should be present with a new baseline eGFR will likely be >45 mL/min/1.73 m2.[19] If any of these criteria are not fulfilled, the patient is not deemed suitable for RN and should undergo PN instead, provided it is safe for the patient.
The European Organization for Research and Treatment of Cancer (EORTC) trial is the only RCT to this date which aimed to compare surgical and oncological outcomes of RN and PN. The results of this study did not reveal any differences in overall survival between these two approaches.[43] Although small retrospective studies have exhibited favorable renal function status with PN, the results of the EORTC contradict these findings.[44],[45]
Further subanalysis of renal function amongst the selected cohort of patients in this study, revealed that NSS may offer certain level of advantage in decreasing the incidence of moderate renal dysfunction, albeit the results did not seem to differ when progression to renal failure was analyzed, which in turn failed to prove that NSS could provide an enhanced survival outcome.[46]
However, this trial has been criticized for several limitations, including failure to meet accrual goals, which was the reason for the premature termination of the study, and the significant portion of patients lost to follow-up.
Follow-Up Monitoring Post-surgical or Ablative ApproachesBoth AUA and EAU guidelines dictate surveillance strategies based on tumor risk stratification.[8],[9] PT1Nx-0 tumors have been classified by both AUA and EAU as low risk and therefore the proposed surveillance intervals have been delineated as follows:
EAU: CT at 6 months, 18 months, and then at 3 years, followed by once every 2 years after the third year.[9] This proposed schedule is for both ablative and surgical approachesAUA: CT or MRI, at 12 months, and then at 24 months, at the 4th year, and annually thereafter, where after 5 years, informed/shared decision-making will guide the need for imaging, for surgical interventions. For post-TA follow-up, a first imaging at 6 months' post-ablation is required, and thereafter, the above interval can be adopted.[8]It should be noted that these surveillance periods are purely based on expert opinion, which calls for high-quality studies assessing the oncological progression and survival outcomes based on these intervals.
Which Management Strategy?To date, one SRMA has been identified by the authors which compares PN, RN, and TA.[47] One of the most important conclusions derived from the results is the significantly large decrease in eGFR following RN, which subsequently played a major role in the development of CKD.[47]
Considering the invasiveness of surgical interventions compared to TA, PN, and RN interestingly offered better local recurrence-free survival rates and an overall survival superiority. However, as previously mentioned, TA is largely offered to patients with advanced age, who often have several comorbidities which in turn affects their morbidity and mortality outcomes.
Patients undergoing PN exhibited increased risk of developing urological complications such as renal abscess, ureteral injury and strictures, and urine leak, as well as higher incidence of blood loss. On the contrary, patients undergoing RN displayed increased evidence of acute kidney injury and other non-urological complications.[47]
Patient-related and tumor-related factors are vital in determining overall morbidity and mortality profiles following treatment. [Figure 1] exhibits a quick overview of management strategies for SRMs. Each management strategy could potentially offer different outcomes for each individual with respect to overall perioperative complications, preservation of renal function, and overall survival rates. Therefore, before making a decision about which treatment to offer to the patient, all variables that would benefit or would put the patient at risk of harmful events should be carefully evaluated.
Data Availability Statement
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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