We report on a series of 14 SFT patients who relapsed after ≥10 years from initial diagnosis (median: 12 years) and were treated thereof at our institution. Their median OS from first diagnosis was 19 years and median OS from first relapse was 8 years. Most patients (70%) relapsed at the site of the primary tumor, with only 3 patients recurring at distant sites without evidence of local relapse. Six patients developed metastatic disease only as late recurrence. No patient was cured, even amongst those undergoing complete salvage surgery of their first local recurrence. However, median OS was 8 years from relapse for all patients, with no major difference between locally relapsing and metastatic patients.
SFT represents a very rare disease and few studies are available on the natural history of this tumor. In particular, few cases of late relapses have been reported [20–26]. They were mostly meningeal and pleural SFTs. Interestingly, none of our patients had a meningeal origin, due to the referral pattern of our institution, and some had other than pleural SFTs. Thus, we can conclude that late relapses are a feature of SFT as such, i.e. they are not confined to meningeal or pleural primary sites. This conclusion can be made even on a limited series of patients, picked up at a single institution on the basis of their unfavourable outcome: thus, selection biases should be taken into account when looking at this retrospective case series analysis.
It is well known that currently available pathologic criteria for defining SFT “malignancy” are not satisfactory. Our series confirms that SFTs can have an aggressive behaviour even in the absence of any morphologic evidence of malignancy at onset. Interestingly, all our patients showed signs of malignancy on relapse. This points to a pathologic evolution which takes place in relapsing SFTs, even when the relapse occurs late. In this sense, it is clear that we need to refine criteria for SFT classification, although available pathologic markers of malignancy clearly correspond to a malignant attitude, having being recorded in all our relapses.
However, aside from those rare cases in which a frank sarcomatous evolution is seen, the malignant features of SFT are consistent with a low-aggressiveness tumor. The clinical counterpart of this conclusion is the long OS of relapsing patients in our series, although the long previous disease-free interval is obviously a bias selecting more indolent cases.
The patterns of relapse we observed emphasize the inherent limitations of surgery in SFT, at least of some typical anatomical sites. In fact, most of our patients first recurred with a multinodular loco-regional relapse, and metastases appeared later on. As observed by many , high rates of local failure are found in epidural, pleural and pelvic/retroperitoneal SFT, while local failure are much rarer with SFT of soft tissues. In other words, SFT arising in the pleural space, or retroperitoneum, or meninges, may well tend to recur “locally” even when they have a benign aspect and are apparently resected in a complete manner, simply because of the inherent limitations of surgery in such anatomical areas. Furthermore, “local” relapse in the pleural space will inevitably lead to pleural dissemination, thus to a pattern of spread which is very similar to a “metastatic” extent. This explains why none of our patients have been cured by salvage treatments, although relapses was loco-regional only in 7. In part, this may also explain why pathologic prognostic criteria are unsatisfactory, the relapse being related to surgical inherent inadequacy much more than to the tumor inherent aggressiveness. On the other side, tumor relapse, whatever its cause, leads to the expression of pathologic markers of higher aggressiveness in all patients. As said above, this is all the more meaningful in our series, which selected late relapses.
Intriguingly, 3 out of 4 patients who were treated with adjuvant radiation therapy did not recur locally while experiencing late metastatic disease. The primary tumor arose from pleural site in 2 cases and from retroperitoneum in 1 case. The literature is inconclusive in regard of adjuvant RT in SFT [32–35]. In a series of 11 SFT treated with definitive RT without surgery, no patient had a local recurrence, and 9 were disease-free at 3 to 20 years from diagnosis . Of course, RT can be hardly advocated in a tumor which, at least retrospectively, is “benign” in 70-80% of cases. However, prospective studies on adjuvant RT in SFT could be conceived when wide surgery is not feasible, as in meningeal, retroperitoneal and pleural presentations, and pathologic signs of “malignancy” are present at the onset.
Our series suggests that late relapses can occur in SFTs, even outside the meningeal setting. However, overall, they seem to be relatively rare. Thus, a prolonged follow-up may be advisable. More importantly, clinicians should be aware that new neoplastic lesions in a patient with a history of SFT can represent a malignant relapse with aggressive disease course, even though the primary tumor displayed “benign” features on pathologic assessment. Current treatment strategies of relapse are clearly insufficient, though reports of activity of new targeted therapies are now available [36–39] so that the outlook of the limited number of SFT patients who relapse may be due to improve in the next future.