Nefrectomía parcial versus nefrectomía radical para masas renales localizadas clínicas
Resumen
Antecedentes
La nefrectomía parcial y la nefrectomía radical son las opciones relevantes de tratamiento quirúrgico para el carcinoma localizado de células renales. Sin embargo, aún continúa el debate con respecto a los efectos de estos enfoques quirúrgicos y es importante identificar y resumir los estudios de alta calidad para realizar recomendaciones en cuanto al tratamiento quirúrgico.
Objetivos
Evaluar los efectos de la nefrectomía parcial comparada con la nefrectomía radical para el carcinoma de células renales clínicamente localizado.
Métodos de búsqueda
Se hicieron búsquedas en CENTRAL, MEDLINE, PubMed, Embase, Web of Science, BIOSIS, LILACS, Scopus, en dos registros de ensayos y en resúmenes de los tres principales congresos hasta el 24 febrero 2017, junto con las listas de referencias; y se estableció contacto con expertos en el tema seleccionados.
Criterios de selección
Se incluyó un ensayo controlado aleatorio que comparaba la nefrectomía parcial y radical en participantes con masas renales pequeñas.
Obtención y análisis de los datos
Un autor de la revisión examinó todos los títulos y resúmenes; solamente las citas que eran claramente irrelevantes se excluyeron en esta etapa. A continuación, dos autores de la revisión evaluaron de forma independiente los informes de texto completo, identificaron los estudios relevantes, evaluaron la elegibilidad de los estudios para su inclusión, evaluaron la calidad de los ensayos y extrajeron los datos. Dos autores de la revisión independientes realizaron la actualización de la búsqueda bibliográfica. Se utilizó Review Manager 5 para la síntesis y análisis de los datos.
Resultados principales
Se identificó un ensayo controlado aleatorio con 541 participantes que comparaba la nefrectomía parcial con la nefrectomía radical. La mediana del seguimiento fue de 9,3 años.
Basado en evidencia de baja calidad, se encontró que el tiempo hasta la muerte por cualquier causa disminuyó al utilizar la nefrectomía parcial (CRI 1,50; IC del 95%: 1,03 a 2,18). Lo anterior corresponde a 79 muertes más (5 más a 173 más) por 1000. También basado en evidencia de baja calidad, no se encontró ninguna diferencia en los eventos adversos graves (CR 2,04; IC del 95%: 0,19 a 22,34). Los resultados son compatibles con 4 muertes más relacionadas con la intervención quirúrgica (3 menos a 78 más) por 1000.
Basado en evidencia de baja calidad, no se encontró ninguna diferencia en el tiempo hasta la recurrencia (CRI 1,37; IC del 95%: 0,58 a 3,24). Lo anterior corresponde a 12 recurrencias más (14 menos a 70 más) por 1000. Debido a la naturaleza del informe, no fue posible analizar las tasas generales para los eventos adversos inmediatos y a largo plazo. No se halló evidencia sobre la hemodiálisis ni la calidad de vida.
Las razones de la disminución de la calidad se relacionaron con las limitaciones de los estudios (falta de cegamiento, cruzamiento), la imprecisión y la imposibilidad para generalizar la evidencia (se encontró que en último término una proporción apreciable de pacientes no presentaba un tumor maligno). Basado en el hallazgo de un único ensayo, no fue posible realizar análisis de subgrupos ni de sensibilidad.
Conclusiones de los autores
La nefrectomía parcial puede asociarse con una disminución del tiempo hasta la muerte por cualquier causa. Con respecto a la mortalidad relacionada con la intervención quirúrgica, la supervivencia específica del cáncer y el tiempo hasta la recidiva, la nefrectomía parcial parece dar lugar a poca a ninguna diferencia.
PICO
Resumen en términos sencillos
Nefrectomía parcial para el tratamiento de los carcinomas renales clínicamente localizados
Pregunta de la revisión
Se examinó la evidencia para comparar los efectos de la eliminación sólo del tumor (nefrectomía parcial) versus la eliminación de todo el riñón (nefrectomía radical) en los individuos con cáncer que presentan un tumor renal pequeño que no se ha propagado a otras partes del cuerpo.
Antecedentes
Los tumores renales pequeños a menudo se descubren en estudios de imagenología (como tomografías computarizadas) pedidos por otras razones. Algunos de estos tumores representan cáncer que puede propagarse a otras partes del cuerpo, causar problemas como hemorragias o dolor e incluso dar lugar a la muerte. La mejor manera de tratar estos tumores es la cirugía para extirpar el tumor. La misma puede realizarse sólo eliminando el tumor (y algo del tejido circundante) o eliminando el tumor y el riñón entero. No se conoce cuál es el mejor procedimiento.
Características de los estudios
Se realizaron búsquedas en la literatura médica hasta el 24 febrero 2017. Se incluyó un estudio con 541 participantes que había asignado al azar a participantes con tumores localizados del riñón considerados cancerosos. En promedio, el seguimiento de los participantes se realizó durante 9,3 años.
Resultados clave
Los participantes que fueron sometidos sólo a la eliminación del tumor parecieron tener una mayor probabilidad de morir por cualquier causa que los participantes en los que se eliminó el tumor y el riñón entero. Pareció haber poca a ninguna diferencia en el tiempo hasta la recidiva del tumor o en el riesgo de complicaciones graves que resultaron en la muerte. No se encontró evidencia sobre cómo se compararon los grupos al considerar la necesidad de hemodiálisis ni cómo se comparó la calidad de vida.
Calidad de la evidencia
La calidad de la evidencia fue baja. Este hecho significa que existe una confianza limitada en los resultados y que el efecto verdadero de la nefrectomía parcial puede ser significativamente diferente.
Authors' conclusions
Summary of findings
| Partial nephrectomy compared to radical nephrectomy for clinical localized renal masses | |||||
| Bibliography: Kunath F, Schmidt S, Krabbe L, Miernik A, Cleves A, Walther M, Kroeger N. Partial nephrectomy versus radical nephrectomy for clinical localized renal masses. Cochrane Database of Systematic Reviews 2017, Issue 3. | |||||
| Outcomes | № of participants | Quality of the evidence | Relative effect | Anticipated absolute effects* (95% CI) | |
| Risk with radical nephrectomy | Risk difference with Partial nephrectomy | ||||
| Time‐to‐death of any cause (anticipated absolute effects refer to all‐cause mortality; median follow‐up duration: 9.3 years) | 541 | ⊕⊕⊝⊝ | HR 1.50 | Study population | |
| 183 per 1.000 | 79 more per 1.000 | ||||
| Serious adverse events (Surgery‐related mortality) | 541 | ⊕⊕⊝⊝ | RR 2.04 | Study population | |
| 4 per 1.000 | 4 more per 1.000 | ||||
| Time‐to‐recurrence (anticipated absolute effects refer to recurrence; median follow‐up duration: 9.3 years) | 541 | ⊕⊕⊝⊝ | HR 1.37 | Study population | |
| 33 per 1.000 | 12 more per 1.000 | ||||
| Permanent haemodialysis ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ |
| Quality of Life ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | |||||
| GRADE Working Group grades of evidence | |||||
| 1 CI consistent with both minimal or large effect size/ small risk or large risk increase (imprecision) 2 Downgraded for lack of blinding (performance bias) 3 Downgraded for lack of blinding (performance and detection bias) 4 Large proportion of subjects did not have malignant tumours (15%; indirectness) | |||||
Background
Description of the condition
Renal cell carcinoma is projected to be associated with 63,990 newly diagnosed kidney cancer cases and 14,400 cancer‐related deaths in 2017 in the United States (Siegel 2017). Due to the increased availability and utilisation of computed tomography (CT) and magnetic resonance imaging (MRI), more renal masses are being detected, and a stage‐migration has occurred during recent years (Cohen 2005; Gill 2010). Incidentally discovered renal masses currently comprise 48% to 66% of tumours, compared with only 3% to 13% in the 1970s (Volpe 2004). While open radical nephrectomy has been the gold standard for any renal tumour surgery in the past, partial nephrectomy is now increasingly employed for renal tumour surgery for clinically localised renal masses.
Description of the intervention
Partial nephrectomy has a long history in kidney surgery. The first documented partial nephrectomy was performed by Vincent Czerny for angiosarcoma in 1887 (Herr 2005). Only a few partial nephrectomies were performed for renal tumours in the following decades. Partial nephrectomy was seen as simply unnecessary when a normal contralateral kidney was present (Herr 2005). Pathological studies by Bell demonstrated that tumours less than 5 cm metastasised in only 7% of cases (Bell 1938). Additionally, Vermooten suggested that tumours could be removed with a safety margin of only 1 cm without an increased risk of recurrence (Herr 2005; Vermooten 1950). However, since small renal tumours can metastasize, most urologists argued that radical nephrectomy should be performed in all cases. Consequently, partial nephrectomy had been mostly reserved for those patients with an imperative indication like a solitary kidney, poor renal function or bilateral tumours. Since the 1970s, urologists began to question this surgical dogma (Herr 2005).
The technique of radical nephrectomy was systematically described by Robson in 1963 (Robson 1963). It was also Robson and colleagues who first described the outcomes of a series of 88 patients treated with radical nephrectomy between 1949 and 1964 (Robson 1969). The most common surgical approaches for radical nephrectomy were thoracoabdominal (transpleural) or, in cases of lower pole tumours, transperitoneal incisions. According to Robson and colleagues, anatomical structures requiring removal are the perinephric fat, overlying peritoneum, and adrenal gland. It was also recommended to routinely perform lymph node dissection of the para‐aortic lymph nodes from the bifurcation of the aorta to the crus of the diaphragm. During recent years, the original technique has been modified. Additional clinical aspects influencing the original approach have been extensively evaluated. For example, it has been shown that the likelihood of adrenal metastases is very low in the absence of pre‐operative radiological signs of adrenal involvement (Kuczyk 2002). Furthermore, even in clinically suspected lymph node metastases, true pathological node positivity is only present in around 20% of these cases, and is far lower in individuals without clinical signs of lymph node involvement (Blom 2009). Routine adrenalectomy, as well as lymphadenectomy, is not recommended as a routine part of partial or radical nephrectomy in the absence of a radiological suspicion of adrenal or nodal involvement (Ljungberg 2015).
The indications for partial nephrectomy have been expanded over the years. Indications have changed from individuals with imperative indications (e.g. solitary kidney, bilateral tumours or high renal insufficiency risk) to all individuals with renal masses less than 4 cm in diameter. Today, guidelines recommend partial nephrectomy whenever technically feasible, independent of tumour size (Campbell 2009; Ljungberg 2015). The rates of partial nephrectomy have increased in past decades, comprising about 30% of all renal surgeries for clinically localised renal masses in 2005 (Bianchi 2013). However, open surgical approaches are still far more common than laparoscopic or robotic‐assisted techniques, although broad adoption of robotic‐assisted surgery has added to the increased utilisation of minimally invasive techniques (Bianchi 2013; Ghani 2014).
Adverse effects of the intervention
Surgical treatments are never without risks and adverse events. For radical nephrectomy, these immediate surgical complications are mainly vascular (severe haemorrhage in 1.2%); however, since the adoption of laparoscopic surgery, blood loss has significantly decreased (Hemal 2007). Splenic injury is seen in less than 1% of patients. Partial nephrectomy is prone to a slightly different spectrum of adverse events. The total rate of adverse events can be as high as 20% to 25% in individuals undergoing partial nephrectomy (Gill 2007; Simhan 2011). The most common adverse events include haemorrhage in 1.2% to 4.5%, urinary fistula in up to 17% and acute renal failure in up to 25% of patients (Ljungberg 2015). Transfusion rates are not routinely reported but can be as high as 50%, while the transfusion rates decline with more experience in partial nephrectomy (Duque 1998).
The adverse events are important due to special considerations in the treated population. Although partial nephrectomy with its inherent complications might be beneficial for a young person who is at risk of additional medical co‐morbidities as well as potential tumour growth in the contralateral kidney, the population of the frail and elderly pose a challenge to the treating surgeon in terms of decision making between the different available techniques. This is of utmost importance because tumours amenable to partial nephrectomy might also be candidate tumours for active surveillance due to the low possibility for significant growth and invasive potential.
How the intervention might work
Renal surgery is a curative treatment option for most individuals with localised renal cell carcinoma. Radical nephrectomy is a safe standard procedure and has demonstrated reliable oncological control. Thus, new surgical approaches have to offer similar cancer‐specific survival rates. On the other hand, surgeons need to consider that the majority of individuals with localised renal cell carcinoma will survive their cancer and therefore every effort has to be made to minimise treatment‐related morbidity. Thus, improved surgical approaches have to induce lower co‐morbidity rates than radical nephrectomy. The most important radical nephrectomy‐related co‐morbidity is renal insufficiency. Partial nephrectomy preserves the part of the kidney uninvolved by the tumour at the time of surgical treatment. Therefore, partial nephrectomy might be associated with lower proportions of surgically induced chronic kidney disease (Kim 2012; MacLennan 2012). Less frequent chronic kidney disease rates may result in better all‐cause outcomes for individuals with localised renal cell carcinoma.
Why it is important to do this review
Partial nephrectomy is a commonly used surgical approach for the growing number of clinically localised renal masses (Tobert 2014). This clinical practice is based on the results of retrospective studies that have strongly suggested the superiority of partial nephrectomy over radical nephrectomy in terms of time‐to‐death of any cause, development of renal insufficiency and even cancer‐specific survival (Tobert 2014). Retrospective studies have shown that tertiary centres primarily use partial nephrectomy routinely (Patel 2012). In light of a perceived under‐utilisation of partial nephrectomy, urological societies have called for the use of partial nephrectomy rather than radical nephrectomy for clinically localised renal masses (Campbell 2009; Ljungberg 2015). The European Association of Urology guidelines state that partial nephrectomy "is recommended in patients with clinical T1a tumours and should be favoured above radical nephrectomy in clinical T1b tumours whenever technically feasible" (Grade A and B recommendations) (Ljungberg 2015). Systematic reviews included not only randomised controlled trials but also several retrospective observational studies (Kim 2012; MacLennan 2012; Gu 2016; Mir 2016; Mir 2016a). The quality of retrospective studies is often strongly impaired by selection bias. However, renal cell carcinoma treatment recommendations of the world's largest urological associations are based on the findings of these retrospective studies (Campbell 2009; Ljungberg 2015). Therefore, it is important to identify and summarise high‐quality studies to make surgical treatment recommendations. Additionally, it is of the utmost importance to summarise the available high‐quality evidence, as well as the gaps in our knowledge, to give clinicians the opportunity to account for the missing information in daily clinical decision making.
Objectives
To assess the effects of partial nephrectomy compared with radical nephrectomy for clinically localised renal cell carcinoma.
Methods
Criteria for considering studies for this review
Types of studies
We considered parallel‐group randomised controlled trials for inclusion and excluded cluster‐randomised trials as well as cross‐over trials as they are not applicable to this disease setting and the type of interventions of interest. We considered studies for inclusion irrespective of their publication status or language of publication.
Types of participants
We considered studies for inclusion that included participants with unilateral localised renal cell carcinoma. We defined localised renal cell carcinoma for the purpose of this review as clinical stage I or stage II, as defined by the 2009 tumour node metastasis (TNM) classification system (Sobin 2010). We made no exclusions based on age or ethnicity. For studies that also included participants with advanced stages of renal cell carcinoma, we initially planned assessing the data only of the subgroup of participants with localised renal cell carcinoma.
Diagnostic criteria for localised renal cell carcinoma
We considered studies for inclusion that included participants with histologically proven renal cell carcinoma. According to the TNM classification, stage I and stage II tumours are defined as:
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Stage I
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T1 (tumor ≤ 7 cm in the greatest dimension, limited to the kidney). T1 is further divided into T1a (≤ 4 cm) and T1b (> 4 cm but ≤ 7 cm).
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N0 (No regional lymph node metastasis).
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M0 (No distant metastasis).
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Stage II
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T2 (tumor > 7 cm in the greatest dimension, limited to the kidney). T2 is additionally divided into T2a (> 7 cm but ≤ 10 cm) and T2b (> 10 cm).
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N0 (No regional lymph node metastasis).
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M0 (No distant metastasis).
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Types of interventions
We investigated the following experimental intervention versus comparator intervention.
Experimental intervention
Partial nephrectomy, defined as surgical extirpation of the renal mass with or without a rim of normal renal parenchyma leaving healthy tissue in place of the ipsilateral renal unit. We planned inclusion of open, laparoscopic and robotic surgical interventions.
Comparator intervention
Radical nephrectomy, defined as surgical extirpation of the whole renal unit including the tumour. We planned the inclusion of open, laparoscopic and robotic surgical interventions.
Comparison
Partial nephrectomy versus radical nephrectomy.
Minimum duration of intervention
We considered studies for inclusion with a minimum follow‐up of 6 months.
Minimum duration of follow‐up
We considered studies for inclusion with a minimum duration of follow‐up of one day after partial or radical nephrectomy.
Extended follow‐up periods (also called open‐label extension studies), defined as a follow‐up of participants once the original trial was terminated as specified in the power calculation for this trial, are frequently of observational nature. We planned inclusion of open‐label extension studies only for evaluation of adverse events.
Specific exclusion criteria
Studies comparing partial nephrectomy with solely ablation therapies for localised renal cell carcinoma, such as radio frequency ablation or cryotherapy, were not considered for inclusion in this review.
Types of outcome measures
We did not exclude studies from the review solely because no outcomes of interest were reported. In cases where none of our primary or secondary outcomes were reported, we planned on excluding the trial but providing some information in an additional table. If we were unable to retrieve the necessary information to analyse time‐to‐event outcomes, we planned to assess the number of events per total for dichotomised outcomes at certain time points.
Primary outcomes
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Time‐to‐death of any cause
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Serious adverse events
Secondary outcomes
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Cancer‐specific survival
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Time‐to‐recurrence
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Immediate post‐operative adverse events
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Long‐term adverse events
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Quality of life
Method and timing of outcome measurement
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Time‐to‐death of any cause, measured at any time after participants were randomised to intervention/comparator groups. The rationale behind selection of time‐to‐death of any cause as a primary outcome measure is to compare both interventions regarding this endpoint, as it is the most important endpoint for participants.
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Serious adverse events. We initially planned that adverse events were considered to be serious when they required hospitalization, were life‐threatening, or fatal, or were reported as such by the authors of the original publication. However, none of them were reported in the included randomised controlled trial and we defined therefore surgery‐related mortality as a serious adverse event.
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Cancer‐specific survival, measured as the date of randomisation to the date of death due to renal cell carcinoma. The rationale behind the endpoint of cancer‐specific survival is to explore the level of oncological control between both interventions.
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Time‐to‐recurrence, measured as the date of randomisation to the date of first clinically detected disease recurrence. The rationale behind the endpoint of time‐to‐recurrence is to explore the level of local oncological control between both interventions, as, with limited follow‐up, time‐to‐recurrence can be used as a surrogate endpoint for cancer‐specific survival.
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Immediate post‐operative adverse events, measured as the date of operation up to 30 days post surgery. We initially planned inclusion of the following adverse events: need for temporary haemodialysis, urinary tract infection, urinary leakage after partial nephrectomy, hemorrhage as well as need for re‐operation or transfusion. The rationale for these outcome measures is the comparison of immediate adverse events which can then be balanced with the rate of oncological control as well as survival between both interventions. However, we included in the evaluation of this review the following reported immediate post‐operative adverse events: spleen damage, pleural damage, perioperative bleeding, urinary fistula, and reoperation due to side‐effects (due to bleeding, urinary fistula, bowel obstruction, pleuropneumonia).
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Long‐term adverse events, measured as 31 days post surgery and after. We initially planned inclusion of the following adverse events: cardiovascular events, hypertension, need for permanent haemodialysis, development of chronic kidney disease (CKD). The rationale for these outcome measures is the comparison of long‐term adverse events which can then be balanced with the rate of oncological control as well as survival between both interventions. However, we included in the evaluation of this review the following reported long‐term adverse events: cardiovascular‐ related mortality, liver‐related mortality, renal‐related mortality, infection‐related mortality, chronic pulmonary disease‐related mortality.
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Quality of life; evaluated by a validated instrument. However, we did not identify a randomised controlled trial assessing quality of life outcomes.
Main outcomes for 'Summary of findings' table
We present a 'Summary of findings' table reporting the following outcomes listed according to priority:
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Time‐to‐death of any cause
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Serious adverse events
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Time‐to‐recurrence
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Permanent need for haemodialysis
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Quality of life
Search methods for identification of studies
We conducted a combination of electronic and manual searches with no restrictions on the language of publication or publication status. See Appendix 1 for full search strategies of each database.
Electronic searches
We searched the following electronic databases:
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Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1) in the Cochrane Library (searched 24 February 2017)
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MEDLINE Ovid SP (In‐Process & Other Non‐Indexed Citations) (1946 to 24 February 2017)
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PubMed (provided by the US National Library of Medicine; epubs from 2013, last searched 24 February 2017)
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Embase OvidSP (1947 to 24 February 2017)
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Web of Science with Conference Citation Proceedings (Thomson Reuters Web of Knowledge; from 1945 to 24 February 2017)
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BIOSIS (from 1985 to 24 February 2017)
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LILACS (from 1986 to 24 February 2017)
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Scopus (from 1960 to 24 February 2017)
We searched the following trials registers.
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World Health Organization International Clinical Trials Registry Platform Search Portal (WHO ICTRP Search Portal; www.who.int/ictrp/en/; no restricted time period, last searched 24 February 2017)
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ClinicalTrials.gov (no restricted time period, last searched 24 February 2017)
We searched the electronically‐available abstracts of the following major national and international urology cancer meetings:
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American Society of Clinical Oncology Annual Meeting (ASCO; jco.ascopubs.org; from 2004, last searched February 28, 2017)
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Annual Meeting of the European Association of Urology (EAU; www.uroweb.org; from 2004, last searched February 28, 2017
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American Urological Association Annual Meeting (AUA; www.jurology.com/; from 2008, last searched February 28, 2017)
We applied a MEDLINE (via Ovid SP) email alert service to identify newly published trials using the same search strategy as described for MEDLINE (for details on search strategies, see Appendix 1). Should we identify new trials for inclusion, we will evaluate these, incorporate the findings into our review and will update this Cochrane Review.
Searching other resources
We screened the reference lists of publications identified as potentially relevant to this review for additional studies. In addition, we contacted leading experts in the field of renal cell carcinoma treatment to request information on unpublished studies (for details see Appendix 2).
Data collection and analysis
Selection of studies
We identified duplicate studies by checking potentially‐relevant studies for author names, locations and settings, details of interventions, numbers of participants, baseline data, study date, and duration of the study using Endnote. We used Covidence for selection of studies, e.g. for the process of selection of included and excluded studies (www.Covidence.org). One review author (FK) screened for relevance all titles and abstracts of records identified by the search. At this stage we excluded only records that were clearly irrelevant (e.g. animal/in vitro research and testing, studies including solely participants with benign tumours). Next, two review authors (FK, SS) independently scanned the abstract, title, or both, of every remaining record to determine which trials we should assess further. Two review authors (FK, SS) independently investigated all potentially‐relevant records as full text, mapped records to studies, and classified studies as included studies, excluded studies, studies awaiting classification, or ongoing studies in accordance with the criteria for each provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b). We resolved any disagreements regarding study eligibility through discussion and consensus or by recourse to a third review author (NK). We documented reasons for exclusion of studies that may have reasonably been expected to be included in the review in a 'Characteristics of excluded studies' table. We include an adapted PRISMA flow diagram showing the process of study selection (Liberati 2009).
Data extraction and management
Two review authors (FK, SS) independently extracted key participant and intervention characteristics using a data extraction form based on the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b). Disagreement was resolved by consensus or, if required, by consultation with a third review author (NK).
We initially planned to provide information, including trial identifier, about potentially relevant ongoing studies in the table 'Characteristics of ongoing studies'. However, we did not identify ongoing randomised controlled trials.
We identified the protocol for the included study (Van Poppel 2007); and compared the reported primary, secondary and other outcomes with data in publications (see 'Characteristics of included studies' table).
We extracted the following information (see 'Characteristics of included studies' table).
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Study design
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Study dates
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Study settings and country
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Participant inclusion and exclusion criteria
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Participant details, baseline demographics (age, gender, co‐morbidities, performance status), tumour characteristics (TNM classification, tumour size, positive surgical margins, renal cell carcinoma subtype, presence of malignancy)
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Number of participants by study and by study arm
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Details of relevant experimental and comparator interventions
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Definitions of relevant outcomes, and method and timing of outcome measurement as well as any relevant subgroups
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Study funding sources
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Declarations of interest by primary investigators
Dealing with duplicate and companion publications
For duplicate publications, companion documents or multiple reports of a primary trial, we maximised the information yield by collating all available data and used the most complete data set aggregated across all known publications (see 'Included studies'). We listed multiple reports of the primary trial as secondary references under the study ID of the included trial.
Data from clinical trial registers
We extracted the data of the included study that were published in clinical trial registers (see 'Characteristics of included studies'). However, we identified no other completed or ongoing registered randomised controlled trials.
Assessment of risk of bias in included studies
Two review authors (FK, SS) independently assessed the risk of bias of each included study using Cochrane's 'Risk of bias' assessment tool (Higgins 2011c). Disagreement was resolved by consensus or through discussion with a third review author (NK). We assessed the following domains.
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Random sequence generation (selection bias due to inadequate generation of a randomised sequence)
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Allocation concealment (selection bias due to inadequate concealment of allocation prior to assignment)
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Blinding of participants and personnel (performance bias due to knowledge of the allocated interventions by participants and personnel during the trial)
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Blinding of outcome assessment (detection bias due to knowledge of the allocated interventions by outcome assessment)
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Incomplete outcome data (attrition bias due to amount, nature or handling of incomplete outcome data)
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Selective reporting (reporting bias due to selective outcome reporting)
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Other sources of bias (bias due to problems not covered elsewhere)
We judged 'Risk of bias' domains as 'low risk', 'high risk' or 'unclear risk' and evaluated individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011c).
The judgements (low, unclear or high risk) were justified in order to maintain transparency, and we indicated the source of information for the 'Risk of bias' judgement by providing a quotation from the study text in the 'Risk of bias' table. We additionally provided a 'Risk of bias' summary figure to illustrate these findings.
The following risk of bias domains were assessed at trial level: random sequence generation, allocation concealment, selective reporting, other sources of bias.
The following risk of bias domains were assessed at outcome level: blinding of participants and study personnel, blinding of outcome assessment, incomplete outcome data.
We defined the following endpoints as subjective outcomes.
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Cancer‐specific survival
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Serious adverse events
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Immediate post‐operative adverse events
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Long‐term adverse events
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Quality of life
We define the following endpoints as objective outcomes.
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Time‐to‐death of any cause
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Time‐to‐recurrence
Measures of treatment effect
We included only one randomised controlled trial and therefore meta‐analyses was not possible. The extracted data were presented using Review Manager 5 (Review Manager 2014). We expressed time‐to‐event outcomes (e.g. time‐to‐death of any cause, cancer‐specific survival, time‐to‐recurrence) as hazard ratios (HR) with 95% confidence intervals (CIs). Results of binary outcomes (e.g. adverse events) were expressed as risk ratios (RRs) with 95% CIs. We identified no study reporting continuous outcomes (e.g. quality of life).
Unit of analysis issues
We included only one parallel‐grouped randomised controlled trial with one intervention and one control group (Van Poppel 2007). Therefore, the unit of analysis was the individual randomised participant. There was a single measurement for each outcome from each participant collected and analysed.
Dealing with missing data
Wherever possible, data were analysed using the intention‐to‐treat (ITT) approach. We carefully evaluated important numerical data such as screened, randomly assigned participants as well as intention‐to‐treat, and per‐protocol populations. We investigated attrition rates (e.g. drop‐outs, losses to follow‐up, withdrawals) and critically appraised issues of missing data. We did not impute missing data.
Assessment of heterogeneity
We included only one randomised controlled trial (Van Poppel 2007). Meta‐analyses with evaluation of heterogeneity were not possible.
Assessment of reporting biases
We included only one randomised controlled trial and did not perform a funnel plot analysis (Van Poppel 2007). We obtained study protocols to assess the possible bias of selective outcome reporting.
Data synthesis
We included only one randomised controlled trial and did not perform a meta‐analysis (Van Poppel 2007). We used Review Manager 5 for creating forest plots (Review Manager 2014). We performed statistical analyses according to the statistical guidelines described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). For dichotomous outcomes, we used the Mantel‐Haenszel method; and for time‐to‐event outcomes, we used the generic inverse variance method. The included study did not report data for continuous outcomes.
Subgroup analysis and investigation of heterogeneity
We initially planned to perform subgroup analyses for the evaluation 'Stage Ia versus Stage Ib renal cell carcinoma' classified by the 2009 TNM classification system (Sobin 2010). However, we included only one randomised controlled trial and could therefore not perform subgroup analyses.
Sensitivity analysis
We initially planned to perform sensitivity analyses in order to explore the influence of the following factors (when applicable) on effect sizes: restricting the analysis by taking into account different follow‐up periods as well as restricting the analysis by taking into account risk of bias, by excluding studies at 'high risk' or 'unclear risk'. However, we included only one randomised controlled trial and could not perform these sensitivity analyses.
'Summary of findings' table
We present the overall quality of the evidence for each outcome specified under 'Types of outcome measures: Summary of finding' according to the GRADE approach, which takes into account issues related not only to internal validity (risk of bias, inconsistency, imprecision, publication bias) but also to external validity, such as directness of results (GRADEpro GDT; Guyatt 2008). Two review authors (FK, SS) independently rated the quality of evidence for each outcome using the 'GRADE Guideline Development Tool' (GRADEpro GDT). In case of disagreement, we consulted the rest of the group and made a judgement based on consensus.
We present a summary of the evidence in a 'Summary of findings' table. It provides key information about the best estimate of the magnitude of the effect, in relative terms and as absolute differences, for each relevant comparison of alternative management strategies, numbers of participants and trials addressing each important outcome and rating of overall confidence in effect estimates for each outcome (Guyatt 2011; Schünemann 2011). We created the 'Summary of findings' table based on the methods described in the Cochrane Handbook for Systematic Reviews of Interventions by means of Review Manager's (RevMan) table editor (Review Manager 2014). We justified all decisions to downgrade the quality of trials using footnotes, and we made comments to aid the reader's understanding of the Cochrane Review where necessary.
Results
Description of studies
For a detailed description of trials, see the 'Characteristics of included studies' and 'Characteristics of excluded studies' sections.
Results of the search
For detailed information on the results of the search, see Figure 1. A total of three articles on only one study were included in this systematic review (Van Poppel 2007). We did not identify any ongoing studies.
Study flow diagram (last searched 28/02/2017)
Included studies
For details on the included studies, see 'Characteristics of included studies' table.
Source of data
All references to the included study were available as full‐text publications in English language (Van Poppel 2007).
Comparisons
The included study compared partial nephrectomy with radical nephrectomy (Van Poppel 2007).
Overview of trial populations
In the included study 541 participants were randomised to either partial nephrectomy (n = 268) or radical nephrectomy (n = 273) (Van Poppel 2007). The trial included subjects with solitary renal masses suspected to be renal cell carcinoma.
Trial design
The included study was a parallel grouped randomised controlled clinical trial with non‐inferiority design (Van Poppel 2007).
Settings
The included multicenter study was conducted at 45 institutions in 17 countries worldwide (Van Poppel 2007).
Participants
Participants with a solitary T1 orT2 N0 M0 renal tumour, suspicious for renal adenocarcinoma with a World Health Organization (WHO) performance status of 2 or less were included. The median age of participants was 62.0 (23.0 to 84.0) years and ranged from younger than 61 years (44.4%), through 61 to 70 years (34.7%) to older than 70 years (20.9%). Collectively, 65.8% of the participants were identified as male and 32.9% as female. The distribution of ethnic groups and of low‐ and middle‐income countries was not reported (Van Poppel 2007). The tumour should not exceed 5 cm in diameter. Participants "with a solitary kidney, von Hippel‐Lindau disease, multifocal disease, T3–T4 tumours, clinical presence of distant or lymphatic metastases, a WHO performance status >2, and participants with another carcinoma, except for adequately treated non‐melanoma skin cancer" were excluded from the study (Van Poppel 2007).
Of the included participants, 85% had malignant tumours. Small renal masses comprised clear‐cell renal cell carcinoma (67.8%), chromophilic renal cell carcinoma (11.5%), chromophobe renal cell carcinoma (3.7%), tumours with sarcomatoid differentiation (0.7%), tumour of the collecting duct (0.4%), leiomyosarcoma (0.2%), lung metastasis (0.2%) as well as angiomyolipoma (3.3%), oncocytoma (6.5%), cysts (1.3%), cystic nephroma (0.2%), leiomyoma (0.2%) and metanephric adenoma (0.4%). Additionally, histological examination was missing in 3% of cases (Van Poppel 2007).
Participants with satellite or secondary lesions found by lymphadenectomy were not excluded (radical nephrectomy n = 14/290; partial nephrectomy n = 4/242; Van Poppel 2007).
Diagnosis
The included participants received physical examination, laboratory evaluation (erythrocyte sedimentation rate, haemoglobin, serum creatinine, alkaline phosphatase), intravenous urography if either microscopic or gross haematuria was present, ultrasonography of the kidney and the liver, chest x‐ray, and a computed tomography scan of both kidneys. The pathologic tumour stage was determined according to the TNM classification system proposed by the Union Internationale Contre le Cancer (UICC; 1978)" (Van Poppel 2007).
Interventions
Radical nephrectomy "consisted of removal of the entire kidney with the adrenal and perinephric fat within the intact Gerota fascia. Limited lymphadenectomy could be done separately or en bloc and included the lymphatic tissue in the renal hilus (usually included in the radical nephrectomy specimen anyway) and the nodes around the vena cava at the level of the renal veins on the right side and on the aorta at the level of the artery on the left side" (Van Poppel 2007).
"The tumour removal was done by excavation (no enucleation), wedge resection, or partial nephrectomy after rigorous inspection of the entire renal capsula together with limited lymphadenectomy. Hilar clamping was not routinely done [...] When there was any doubt about the margin status, a frozen section analysis of the resection margins was performed. In the case of a positive resection margin, satellite or secondary lesions, radical nephrectomy was done" (Van Poppel 2007).
Overall, different surgical approaches were included whereby the most frequently applied surgical method for radical nephrectomy was laparotomy (53.6%); and for partial nephrectomy, flank incision (69.9%) (Van Poppel 2007).
Outcomes
The primary end point was time‐to‐death of any cause. Secondary end points were cancer‐specific survival, time‐to‐recurrence and adverse events.
Excluded studies
We excluded 137 articles after evaluation of the full publication. The main reason for exclusion was a non‐randomised study design. For further details on reasons for study exclusions see 'Characteristics of excluded studies' table.
Risk of bias in included studies
For details on the risk of bias of the included trial see 'Characteristics of included studies' table. For an overview of review authors' judgements about each risk of bias item see Figure 2 and summary of findings Table for the main comparison.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Allocation
Random sequence generation
We assume that randomisation was performed adequately at the EORTC Data Centre. However, information was not reported and therefore we judged the risk of bias to be unclear.
Allocation concealment
There was a central allocation and we judged the risk of bias to be low.
Blinding
Blinding of participants and personnel
The included study was an open randomised trial and did not involve blinding of the participants and/or personnel. For detail on our assessment of this risk of bias domain that we assessed at outcome level for objective and subjective outcomes, see 'Characteristics of included studies' section.
Blinding of outcome assessment
The included study did not involve blinding of the outcome assessment (or blinding was not reported). We judged that outcome assessment for objective outcomes are not likely to be influenced by lack of blinding (low risk of bias). However, we judged that subjective outcomes may have been influenced by lack of blinding, leading to high risk of bias (Characteristics of included studies).
Incomplete outcome data
Time‐to‐death of any cause, time‐to‐recurrence, cancer‐specific survival, serious adverse events and long‐term adverse events were analysed by intention‐to‐treat and all randomized participants were included in the analyses for these outcomes. We judged the risk of bias to be low.
Evaluation of immediate post‐operative adverse events was an ‘as‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation leading to high risk of bias. We were unable to obtain the necessary data to re‐analyze as per intention‐to‐treat.
Selective reporting
There is low risk of reporting bias because the study protocol is available and we were able to confirm that the published reports include all expected outcomes.
Other potential sources of bias
The 541 participants were randomized to either partial nephrectomy (n = 268) or radical nephrectomy (n = 273) but a large proportion of participants crossed over from the intervention to the control group and vice versa. Of the 268 participants randomized to partial nephrectomy, 39 received radical nephrectomy. Of the 273 participants randomized to radical nephrectomy, 16 received partial nephrectomy.
Effects of interventions
1. Partial nephrectomy versus radical nephrectomy
Primary outcomes
1.1 Time‐to‐death of any cause
Partial nephrectomy was associated with a reduced time‐to‐death of any cause (HR 1.50, 95% CI 1.03 to 2.18; 541 participants; Analysis 1.1), which corresponded to 79 more deaths per 1000 (95% CI 5 more to 173 more per 1000) after a median follow‐up duration of 9.3 years. The quality of evidence was rated as low due to study limitations and imprecision (summary of findings Table for the main comparison).
1.2 Serious adverse events (Surgery‐related mortality)
Deviating from the published protocol (Krabbe 2016), we redefined surgery‐related mortality as a serious adverse event because no adverse event was reported that was named serious by the authors, yet surgery related mortality appeared important and closely related. Only three subjects in this trial died due to surgery, two in the partial nephrectomy arm and one in the radical nephrectomy arm. The RR of surgery related mortality was 2.04 (95 % CI 0.19 to 22.34; 541 participants; Analysis 1.2). This corresponded to four more events per 1000 participants (95% CI 3 fewer to 78 more). The quality of the evidence for this outcome was low (summary of findings Table for the main comparison). We downgraded for study limitations and imprecision (summary of findings Table for the main comparison).
Secondary outcomes
1.3 Cancer‐specific survival
Cancer‐specific survival was similar between groups with a HR of 2.06 (95 % CI 0.62 to 6.84; 541 participants; Analysis 1.3).
1.4 Time‐to‐recurrence (local recurrence/lymph node metastases, distant metastases)
Time‐to‐recurrence was similar between groups with a HR of 1.37 (95% CI 0.58 to 3.24; 541 participants; Analysis 1.4). The quality of the evidence for this outcome was low (summary of findings Table for the main comparison).
1.5 Immediate post‐operative adverse events
1.5.1 Spleen damage
There was no difference between partial or radical nephrectomy for spleen damage (RR 1.99, 95% CI 0.18 to 21.84; 529 participants; Analysis 1.5).
1.5.2 Pleural damage
There was no difference between partial or radical nephrectomy for pleural damage (RR 1.12, 95% CI 0.67 to 1.86; 529 participants; Analysis 1.6).
1.5.3 Perioperative bleeding
The risk for perioperative bleeding was increased for partial nephrectomy if compared with radical nephrectomy (RR 1.94, 95% CI 1.38 to 2.73; 529 participants; Analysis 1.7).
1.5.4 Urinary fistula
The risk for urinary fistula was increased with partial nephrectomy if compared to radical nephrectomy (RR 20.92, 95% CI 1.23 to 355.20; 529 participants; Analysis 1.8).
1.5.5 Reoperation due to side‐effects (due to bleeding, urinary fistula, bowel obstruction, pleuropneumonia)
There was no difference between partial or radical nephrectomy for reoperation due to side effects (RR 1.83, 95% CI 0.69 to 4.87; 529 participants; Analysis 1.9).
1.5.6 Urinary tract infection
We did not find evidence for this outcome.
1.5.7 Temporary haemodialysis
We did not find evidence for this outcome.
1.6 Quality of life
We did not find evidence for this outcome.
1.7 Long‐term adverse events
1.7.1 Cardiovascular‐related mortality
There was no difference between partial or radical nephrectomy for cardiovascular‐related mortality (RR 1.27, 95% CI 0.72 to 2.24; 541 participants; Analysis 1.10).
1.7.2 Liver‐related mortality
There was no difference between partial or radical nephrectomy for liver‐related mortality (RR 9.17, 95% CI 0.50 to 169.45; 541 participants; Analysis 1.11).
1.7.3 Renal‐related mortality
There was no difference between partial or radical nephrectomy for renal‐related mortality (RR 2.04, 95% CI 0.62 to 6.69; 541 participants; Analysis 1.12).
1.7.4 Infection‐related mortality
There was no difference between partial or radical nephrectomy for infection‐related mortality (RR 0.68, 95% CI 0.11 to 4.03; 541 participants; Analysis 1.13).
1.7.5 Chronic pulmonary disease‐related mortality
There was no difference between partial or radical nephrectomy for chronic pulmonary disease‐related mortality (RR 1.53, 95% CI 0.26 to 9.07; 541 participants; Analysis 1.14).
1.7.6 Cardiovascular events
We did not find evidence for this outcome.
1.77 Hypertension
We did not find evidence for this outcome.
1.78 Permanent haemodialysis
We did not find evidence for this outcome.
1.79 Development of chronic kidney disease (CKD)
We did not find evidence for this outcome.
Subgroup analyses
We did not perform subgroups analyses because we only found a single trial. Additionally, the identified study did not present information in such a way as to permit additional analyses.
Sensitivity analyses
We performed none of the predefined sensitivity analyses due to the limited number of trials (n = 1).
Assessment of reporting bias
We did not draw funnel plots due to the limited number of trials (n = 1).
Ongoing trials
We found no ongoing randomised controlled trials.
Discussion
Summary of main results
Based on a single randomised controlled trial, we found that partial nephrectomy was associated with a reduced time‐to‐death of any cause, whereas serious adverse event rates, cancer‐specific survival and time‐to‐recurrence were similar between the two groups. However, the quality of evidence for each of these outcomes was low, indicating that our confidence in this effect estimate is limited; the true effect may be substantially different from the results of our analysis. We did not find evidence for the outcomes of permanent haemodialysis or quality of life.
Overall completeness and applicability of evidence
We found a single randomised controlled trial that addressed our focused clinical question. In contrast to our predefined patient population of interest (patients with localised renal cell carcinoma), this trial enrolled patients with clinically suspected renal cell carcinoma leading to a patient population with 15% benign tumours and participants with secondary lesions found by lymphadenopathy. However, this may correspond to a patient population of clinical routine.
The central limitation of this review is its focus on randomised controlled trials only, which is consistent with past Cochrane methods. Given that we only found low quality evidence for all reported outcomes, it is possible that well‐designed observational studies, in particular those using advanced statistical methods to address potential confounding, such as propensity weighting or instrumental variable analysis to address potential confounding, might have yielded higher quality evidence to help inform this question. In the absence of additional future randomised controlled trials, which appear unlikely, future updates of this review may formally incorporate evidence from prospective comparative observational studies (Schunemann 2013).
Quality of the evidence
We rated the quality of evidence as low for all outcomes (summary of findings Table for the main comparison). Consistent issues that impacted all outcomes were lack of blinding, raising concerns about performance and detection bias; and cross‐over, posing a risk of selection bias; and imprecision. In summary, the included study has methodological limitations leading to downgrading of the quality of evidence (Van Poppel 2007) (summary of findings Table for the main comparison).
Potential biases in the review process
We searched multiple databases, including clinical trial registers, and contacted selected experts regarding the therapy of small renal masses. We believe that it is not likely that we have overlooked further relevant published or unpublished randomised controlled trials. However, it might be conceivable that we could have potentially missed additional trials in a language other than English that were not registered and were perhaps done relatively long ago.
Agreements and disagreements with other studies or reviews
The focus of this systematic review on randomised controlled trials is consistent with Cochrane methods for obtaining the best available evidence. The inclusion of only randomised controlled trials may be susceptible to bias due to the inclusion of highly selected participants and a small sample size leading to potential underestimation of rare but serious adverse events (Chou 2010). There are also other systematic reviews available evaluating the effect of partial and radical nephrectomy including retro‐ and prospective comparative observational studies (Kim 2012; MacLennan 2012; Gu 2016; Mir 2016; Mir 2016a; Tobert 2014). None of the existing systematic reviews evaluated the quality of evidence according to GRADE although they frequently highlighted the methodological limitations of existing studies. Non‐randomised studies often contain more participants with a long follow‐up showing an increased external validity (Gartlehner 2008) and are particularly suitable for the evaluation of serious and/or rare adverse events. However, results of systematic reviews of non‐randomised studies should be interpreted carefully because of the risk of selection bias and confounding. A matched cohort study using the Surveillance, Epidemiology, and End Results (SEER)‐Medicare dataset demonstrated that partial nephrectomy improved overall survival compared with non‐cancer controls. The authors concluded that apparent survival advantage conferred by partial nephrectomy is likely the result of selection bias involving unmeasured confounders (Shuch 2013). This was also a conclusion of Taubert et al. (Tobert 2014). There is evidence that in non‐randomised studies partial nephrectomy was more frequently used in younger patients, in patients who had fewer co‐morbidities, smaller tumour size, less aggressive pathology, lower Charlson scores, lower American Society of Anesthesiologists (ASA) score, less symptoms at presentation, better renal function and better quality of life scores compared with radical nephrectomy (Arnold 2013; Baillargeon Gagné 2010; Kaushik 2013; Kopp 2013; Lane 2010; Mano 2015; Matin 2002; Milonas 2013; Poulakis 2003; Simmons 2009; Takagi 2015; Vourganti 2011; Weight 2009; Woldrich 2012; Yasuda 2013; Zorn 2007).
The included study presented no information for our predefined outcome of permanent haemodialysis although it did include some information regarding postoperative renal function based on serum creatinine values. We did not include these results because this was not a predefined outcome of our review given its surrogate nature. In this trial after a median follow‐up of 6.7 years, the risk of experiencing reduced renal function (estimated glomerular filtration rate (eGFR) < 60) was reduced with partial nephrectomy when compared with radical nephrectomy (RR 0.65, 95% CI 0.54 to 0.79; 514 participants; Van Poppel 2007). While the preservation of renal function appears desirable in all patients, it is uncertain how important this is in patients with a normally functioning contralateral kidney and a normal renal function at baseline. For example, it has been suggested that radical nephrectomy may be the preferred approach in older patients given that any renal function benefit is only realized over an extended period of time (An 2017).
Quality of life is an important outcome that was not assessed in this trial. A retrospective study has suggested that quality of life differences may already exist at baseline among patient in patients undergoing partial and radical nephrectomy in clinical practice (Arnold 2013), therefore emphasizing the risk of selection bias in observational studies which needs to be controlled for.
Relevant for evaluation of partial nephrectomy is the rate of local and distant disease recurrence. The included study presented no difference between partial or radical nephrectomy regarding time‐to‐recurrence. This result is consistent with the findings of other available evidence (Gu 2016). Several non‐randomised studies presented data supporting that there may be no difference between the different surgical approaches in localised (T1a‐b) (Antonelli 2008; Antonelli 2012; Barbalias 1999; Blute 2006; Indudhara 1997; Kim 2010; Koo 2016; Li 2009a; Mano 2015; Mariusdottir 2013; McKiernan 2002; Minervini 2012; Mitchell 2006; Roos 2011a; Simmons 2009) and even in participants with more advanced stages (T3a N0 M0) of renal cell carcinoma (Polo 2012; Simmons 2009). Predictive factors for a decreased time‐to‐recurrence after 5 years from surgery may be lymphovascular invasion, Fuhrmann grade 3/4, tumour stage >T1, positive surgical margin, symptoms at presentation, macroscopic necrosis, and sarcomatoid differentiation (Abel 2010; Brookman May 2013; Brookman May 2013a; Koo 2016; Polo 2012).
Study flow diagram (last searched 28/02/2017)
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 1 Time‐to‐death of any cause.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 2 Serious adverse events (Surgery‐related mortality).
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 3 Cancer‐specific survival.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 4 Time‐to‐recurrence.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 5 Spleen damage.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 6 Pleural damage.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 7 Perioperative bleeding.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 8 Urinary fistula.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 9 Reoperation due to side‐effects (due to bleeding, urinary fistula, bowel obstruction, pleuropneumonia).
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 10 Cardiovascular‐related mortality.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 11 Liver‐related mortality.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 12 Renal‐related mortality.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 13 Infection‐related mortality.
Comparison 1 Partial nephrectomy vs. radical nephrectomy (intention‐to‐treat), Outcome 14 Chronic pulmonary disease‐related mortality.
| Partial nephrectomy compared to radical nephrectomy for clinical localized renal masses | |||||
| Bibliography: Kunath F, Schmidt S, Krabbe L, Miernik A, Cleves A, Walther M, Kroeger N. Partial nephrectomy versus radical nephrectomy for clinical localized renal masses. Cochrane Database of Systematic Reviews 2017, Issue 3. | |||||
| Outcomes | № of participants | Quality of the evidence | Relative effect | Anticipated absolute effects* (95% CI) | |
| Risk with radical nephrectomy | Risk difference with Partial nephrectomy | ||||
| Time‐to‐death of any cause (anticipated absolute effects refer to all‐cause mortality; median follow‐up duration: 9.3 years) | 541 | ⊕⊕⊝⊝ | HR 1.50 | Study population | |
| 183 per 1.000 | 79 more per 1.000 | ||||
| Serious adverse events (Surgery‐related mortality) | 541 | ⊕⊕⊝⊝ | RR 2.04 | Study population | |
| 4 per 1.000 | 4 more per 1.000 | ||||
| Time‐to‐recurrence (anticipated absolute effects refer to recurrence; median follow‐up duration: 9.3 years) | 541 | ⊕⊕⊝⊝ | HR 1.37 | Study population | |
| 33 per 1.000 | 12 more per 1.000 | ||||
| Permanent haemodialysis ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ |
| Quality of Life ‐ not measured | ‐ | ‐ | ‐ | ‐ | ‐ |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | |||||
| GRADE Working Group grades of evidence | |||||
| 1 CI consistent with both minimal or large effect size/ small risk or large risk increase (imprecision) 2 Downgraded for lack of blinding (performance bias) 3 Downgraded for lack of blinding (performance and detection bias) 4 Large proportion of subjects did not have malignant tumours (15%; indirectness) | |||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Time‐to‐death of any cause Show forest plot | 1 | 541 | Hazard Ratio (Random, 95% CI) | 1.50 [1.03, 2.18] |
| 2 Serious adverse events (Surgery‐related mortality) Show forest plot | 1 | 541 | Risk Ratio (M‐H, Random, 95% CI) | 2.04 [0.19, 22.34] |
| 3 Cancer‐specific survival Show forest plot | 1 | 541 | Hazard Ratio (Random, 95% CI) | 2.06 [0.62, 6.84] |
| 4 Time‐to‐recurrence Show forest plot | 1 | 541 | Hazard Ratio (Random, 95% CI) | 1.37 [0.58, 3.24] |
| 5 Spleen damage Show forest plot | 1 | 529 | Risk Ratio (M‐H, Random, 95% CI) | 1.99 [0.18, 21.84] |
| 6 Pleural damage Show forest plot | 1 | 529 | Risk Ratio (M‐H, Random, 95% CI) | 1.12 [0.67, 1.86] |
| 7 Perioperative bleeding Show forest plot | 1 | 529 | Risk Ratio (M‐H, Random, 95% CI) | 1.94 [1.38, 2.73] |
| 8 Urinary fistula Show forest plot | 1 | 529 | Risk Ratio (M‐H, Random, 95% CI) | 20.92 [1.23, 355.20] |
| 9 Reoperation due to side‐effects (due to bleeding, urinary fistula, bowel obstruction, pleuropneumonia) Show forest plot | 1 | 529 | Risk Ratio (M‐H, Random, 95% CI) | 1.83 [0.69, 4.87] |
| 10 Cardiovascular‐related mortality Show forest plot | 1 | 541 | Risk Ratio (M‐H, Random, 95% CI) | 1.27 [0.72, 2.24] |
| 11 Liver‐related mortality Show forest plot | 1 | 541 | Risk Ratio (M‐H, Random, 95% CI) | 9.17 [0.50, 169.45] |
| 12 Renal‐related mortality Show forest plot | 1 | 541 | Risk Ratio (M‐H, Random, 95% CI) | 2.04 [0.62, 6.69] |
| 13 Infection‐related mortality Show forest plot | 1 | 541 | Risk Ratio (M‐H, Random, 95% CI) | 0.68 [0.11, 4.03] |
| 14 Chronic pulmonary disease‐related mortality Show forest plot | 1 | 541 | Risk Ratio (M‐H, Random, 95% CI) | 1.53 [0.26, 9.07] |
