Abstract: We examined 1069 publications, scrutinized 42 full-text publications or records, and included five RCTs. Altogether, 244 participants entered the five trials; 127 participants were randomised to retroperitoneal adrenalectomy and 117 participants to transperitoneal adrenalectomy. Two trials had a follow-up of nine months, and three trials a follow-up of 31 to 70 months. Most participants were women, and the average age was around 40 years. Three trials reported all-cause mortality; in two trials, there were no deaths, and in one trial with six years of follow-up, four participants died in the LRPA group and one participant in the LTPA group (164 participants; low-certainty evidence). The trials did not report all-cause morbidity. Therefore, we analysed early and late morbidity, and included specific adverse events under these outcome measures. The results were inconclusive between LRPA and LTPA for early morbidity (usually reported within 30 to 60 days after surgery; RR 0.56, 95% CI 0.27 to 1.16; P = 0.12; 5 trials, 244 participants; very low-certainty evidence). Nine out of 127 participants (7.1%) in the LRPA group, compared with 16 out of 117 participants (13.7%) in the LTPA group experienced an adverse event. Participants in the LRPA group may have a lower risk of developing late morbidity (reported as latest available follow-up; RR 0.12, 95% CI 0.01 to 0.92; P = 0.04; 3 trials, 146 participants; very low-quality evidence). None of the 78 participants in the LRPA group, compared with 7 of the 68 participants (10.3%) in the LTPA group experienced an adverse event. None of the trials reported health-related quality of life. The results were inconclusive for socioeconomic effects, assessed as time to return to normal activities and length of hospital stay, between the intervention and comparator groups (very low-certainty evidence). Participants who had LRPA may have had an earlier start on oral fluid or food intake (MD -8.6 hr, 95% CI -13.5 to -3.7; P = 0.0006; 2 trials, 89 participants), and ambulation (MD -5.4 hr, 95% CI -6.8 to -4.0 hr; P < 0.0001; 2 trials, 89 participants) than those in the LTPA groups. Postoperative and operative parameters (duration of surgery, operative blood loss, conversion to open surgery) showed inconclusive results between the intervention and comparator groups. The body of evidence on laparoscopic retroperitoneal adrenalectomy compared with laparoscopic transperitoneal adrenalectomy is limited. Late morbidity might be reduced following laparoscopic retroperitoneal adrenalectomy, but we are uncertain about this effect because of very low-quality evidence. The effects on other key outcomes, such as all-cause mortality, early morbidity, socioeconomic effects, and operative and postoperative parameters are uncertain. LRPA might show a shorter time to oral fluid or food intake and time to ambulation, but we are uncertain whether this finding can be replicated. New long-term RCTs investigating additional data, such as health-related quality of life, surgeons' level of experience, treatment volume of surgical centres, and details on techniques used are needed.

Plain-language summary: We found five randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups) with 244 participants. A total of 127 participants were randomised to retroperitoneal adrenalectomy and 117 participants to transperitoneal adrenalectomy. Two studies had an observation period after surgery of nine months. Three studies observed their participants for 31 to 70 months. Most participants were women, and the average age was around 40 years. This evidence is up to date as of April 2018. In the short-term period after surgery, no deaths were reported for either adrenalectomy technique. One study with a six-year observation period, reported that out of 164 participants, four participants from the retroperitoneal adrenalectomy group died, and one participant from the transperitoneal adrenalectomy group died. We compared early poor health (morbidity), reported after 30 to 60 days, and late morbidity, reported at the longest observation time after surgery. Early morbidity was comparable between the two techniques, but late morbidity might be lower following retroperitoneal adrenalectomy (none out of 78 participants) than following transperitoneal adrenalectomy (7 out of 68 participants). No study reported on health-related quality of life. Time to return to normal activities, length of hospital stay, duration of surgery, operative blood loss, and a change to open surgery were comparable between the two techniques. Time to oral fluid or food intake and time getting out of bed and engaging in light activity seemed a couple of hours shorter following retroperitoneal adrenalectomy (on average 8.6 hours) compared to transperitoneal adrenalectomy (on average 5.4 hours). We are uncertain which adrenalectomy technique is best, mainly because of the small number of studies, small number of participants, and some systematic errors in the majority of our analysed studies. New studies should especially investigate health-related quality of life. Surgeons' level of experience and treatment volume of surgical centres might also influence results.