Thymectomy is a therapeutic option in the management of treatment of patients with myasthenia gravis and positive anti-AchR Ab. However, its effectiveness has only been proven in a randomized controlled trial adopting sternotomic thymectomy among specific inclusion criteria: onset of MG 3 years before surgery, age of 18–65 years, a serum acetylcholine-receptor–antibody level of more than 1.00 nmol/l, and an MGFA score from II to IV [3]. Nevertheless, a substantial proportion of patients in real-world cohorts do not reach complete stable remission after thymectomy indicating that the underlying autoimmune process is sustained in the peripheral lymphatic organs [5,6,7]. With the significant changes in surgical practice and the increase of elderly population in good clinical condition, the inclusion of MG patients over 65 years to radical thymectomy is questionable and deserves more evidence-based studied. Data in literature already report good results for people aged less than 65, with both open and RATS approach, with some studies reporting a rate of CSR variable between 50 and 60% after surgery, in non-thymomatous patients affected by MG, but evidences are limited and still inconsistent [8,9,10,11].

In the present manuscript, we aim to add further data on the neurological efficacy of thymectomy in patients with MG older than 65, who presented with thymic epithelial tumour and for which surgery was indicated for oncological purpose mainly, with few cases in which it was indicated firstly for the neurological outcome (i.e. Osserman score preop 3 or 4).

Firstly, we observed that only a small percentage (10.5%) of patients was neurologically unchanged or had worsening after surgery, according to the MGFA-PIS. The greatest number presented with a minimal manifestation outcome after surgery (65.2%), with a reduction of the need of pharmacological treatment. An encouraging (but still to be consolidated) result also emerged, with a total of 15 patients (22.5%) having complete stable remission (#4) and pharmacological remission (#11).

To the best of our knowledge, not many studies in literature have focused on this particular population of thymoma patients aged over 65, affected with MG and treated with surgery. Romano and colleagues, in a recent study, analysed the neurological outcome after robotic thymectomy for thymoma in patients affected with MG [12]. They obtained improvement of the clinical conditions in 26 patients (76.5%) following the operation: complete stable remission was observed in 5 patients (14.7%), pharmacological remission in 10 (29.4%), and minimal manifestation in 11 (32.3%) [12]. Interestingly, their patients were similar to ours according to the neurological and oncological disease, but the series of Romano and colleagues was composed of patients with a mean age of 52.6 years. The results on neurological outcome are in line with ours, suggesting that surgery is still a good option for patients with these features, but they are still analysing patients under 65 years. Another interesting finding was from Jiao and coworkers, who studied the surgical safety in myasthenia gravis (MG) patients aged > 65 years in a cohort of 564 patients with MG who underwent surgery [13]. In this case, rather than the neurological outcome, they considered the surgical outcome, and concluded that surgical indications should be considered in each elderly MG patient on an individual base. Moreover, most elderly MG patients safely survive the perioperative period, suggesting a low morbidity/mortality rate correlated to MG exacerbation.

On the other hand, Otsuka and colleagues evaluated the long-term clinical outcomes after extended thymectomy in 30 MG patients with or without thymoma [14]. In their cohort, nine patients were over 65 years old. Overall, the symptoms of MG improved in four of the nine (44%) elderly patients only. None of the elderly patients achieved complete stable remission. They concluded that thymectomy can be an option even in elderly patients and suggested performing surgery in a short interval after the onset of MG, better if shorter than 1 year. The population studied by Otsuka and coworkers was very small, and even smaller was the number of patients over 65, so the results are far from being conclusive. In this framework, the present analysis, despite being limited in sample size, is one the biggest reported till now on this topic.

Cunha and coworkers analysed the effect of thymectomy both in patients affected and not affected by thymoma. Their results showed that the cohort affected with thymoma was older than the one of not affected patients (mostly older than 54 years), and they had a good neurological outcome, with a reduction in medication need. In particular, according to their findings, the better outcome was for the ones with an interval between the MG development and surgery shorter than 1 year [15].

Another interesting observation is from Tian and colleagues. In their paper, they analysed the impact of thymoma on neurological outcome in patients affected by thymoma and myastenia gravis. Surprisingly, they found out that thymectomy was associated with a better neurological outcome above all in patients older than 50 years. It is interesting to notice that according to this experience, surgery is associated with a better outcome if MG history before surgery is longer than 1 year, which is in contrast with the findings from Otsuka and Cunha [16].

This is an interesting observation; in particular, in our cohort the mean interval between the onset of MG and surgery was 1.7 years. According to our analysis, no statistical difference was found between patients operated within 12 months from the onset of MG and patients operated after 12 months.

We also tried to evaluate the possible features predicting the neurological outcome, but no statistical association was found when exploring all the clinical pre/postoperative variables and oncological characteristics. In particular, we found no association with the kind of surgical approach (minimally invasive vs open approach), the tumour dimension, the age of onset of the MG, the preoperative pharmacological treatment, and the preoperative Osserman score. These results may suggest that the neurological effect is comparable when performing radical thymectomy by open techniques (mostly sternotomy) or mini-invasive techniques (RATS and VATS) surgery. In this sense, mini-invasive surgery that has been reported to be linked to a better perioperative outcome [9] may be proposed as part of the treatment of MG and can be offered also to patients aged over 65, without a real selection based on other variables (a part from a general clinical selection before surgery). Indeed, if few years ago the surgical approach consisted mainly of standard open approach (sternotomy or thoracotomy), nowadays, the indications for robotic as well as thoracoscopic-assisted thymectomy are being studied [12]. Salahoru and coworkers, in their review, already concluded that minimally invasive approaches as videothoracoscopic surgery or robotic surgery led to a decrease in the length of hospital stay for these patients, with all the advantages related to a shorter stay in the hospital [17]. In particular, robotic thymectomy should improve cosmetic results, reduce postoperative pain, and allow accelerated recovery for patients with MG [18].

A really recent paper, from Nawojowska and colleagues, describes the videothoracoscopic approach in the treatment of myasthenia gravis to be non-inferior compared to the open approach,h offering all the additional benefits of less invasive surgery [19].

Furthermore, in the coming years, the average age of the population is growing, so patients aged over 65 will increase (increasing the number of patients potentially affected by MG in this age).

From a clinical prospective, there is a lack of evidence in this filed and, presently, the opportunity to perform a thymectomy after the clinical onset of MG in patients aged more than 65 years is very questionable and deserves more data for an evidence-based approach. Potentially, nowadays a radical thymectomy, performed by a mini-invasive approach (associated with a faster recovery with less complications compared to the open approach), could be an option also in patients aged over 65 affected with MG, if further analysis will suggest a neurological benefit as well as in the other classes of age. In support of this consideration, Bertoglio and colleagues reported that minimally invasive thymic surgery (both VATS and RATS), even if extended to more than one surrounding organ, is related to a lower incidence of postoperative complications and shorter postoperative length of stay, even in patients that require extended resections [20].

In our series, a superior age limit had not been posed as potentially, if the performance status is adequate, with all the preoperative evaluation confirming that surgery can be offered. Even if, as stated at the beginning, part of the population does not reach a CSR, no features, from our experience, seem to predict the neurological response. Probably, immunological factors, such as the anti-Ach Ab titre, are responsible for the different neurological responses [21, 22]. More oriented studies on the immunological response are necessary to define if a substratification of patients as candidates to surgery can be done.

The main limitation of our study is that our cohort was composed of patients candidate to surgery for oncological purpose and not for neurological reasons. Thus, the neurological outcome after surgery cannot be compared to the one of patients affected only with MG without thymoma, because the biology of the neurological disease could be potentially differentOur results seem to be an interesting starting point to analyse over 65 years old patients affected only with MG and so to extend the indication for surgery in elderly patients. Furthermore, another limitation is the small number of patients, the retrospective nature of our study, and the possible heterogeneity of our data due to the bicentric origin of our sample.