The Effect of Salvage Radiotherapy on Survival, Functional Outcomes and Quality of Life in Men with Persistent PSA after Robot-assisted Radical Prostatectomy; Which Patient Benefits More?- Beyond the Abstract

A significant number of men have persisting measurable prostate specific antigen (PSA) levels (>0.1ng/ml) after radical prostatectomy (RP), indicating a spectrum of prospect clinical courses of prostate cancer (PCa) after surgery; cancer in surgical site, understaged metastasis or circulating cancer cells.1 As salvage radiotherapy (sRT) is an excellent local treatment option for the first possibility aforementioned, the others are needed systemic treatments. Thus, patient selection for proper treatment options in this heterogeneous group takes place with great importance.


In this study, we aimed to depict the sRT outcomes in a broad aspect. Primary endpoint of the study was mid-term survival (median follow-up time of 4.5 years) along with important secondary outcomes; patient-reported functional outcomes and quality of life. More importantly, we pursued the answer that revealing subgroups that benefit more from sRT.

From our prospectively maintained institutional database, 313 patients with persistent PSA were included in the analysis. Patients who have persistent PSA were 9.2% of the overall robot-assisted RP cohort. With acceptable shrinking of sample size, 1:1 propensity score matching yielded 109 sRT+ versus 109 sRT- patients. We took pathological tumor stage (pT), lymph node involvement (pN), surgical margin status, and Gleason score into account as subgrouping variables.

Along with positive surgical margin, patients who have more advanced (higher pT and pN stage) disease had more survival benefits with sRT, suggesting these loco-regional features that picture resected tumor’s anatomy also surrogate the dosable residual cancer tissue in the surgical site. Even though these findings were in line with the largest study in the literature including a RT naive control group, Gleason score acted the other way around in our study.2 Patients with lower Gleason scores were more likely to have more survival benefits from sRT. Gleason score represents progression potential of tumor and probably it is associated with radiosensitivity of PCa. A gene study showed that microRNAs which has increased expression in higher Gleason score can promote radiation resistance.3 But still we need more data to support this finding clinically.

Bowel symptoms were observed more frequently in sRT+ patients compared to sRT- patients (34.3% versus 19.2%, p=0.01) especially when sRT administered <6 months postoperatively (p=0.03). Early sRT was also associated with bothering incontinence (p<0.001).

In conclusion, it seems that high Gleason scores not only increase the distant metastasis risk but also promote the radiation resistance of tumor cells. Even though they picture removed tumor’s anatomy, pT and pN stage are good surrogates of loco-regional residual disease after RP. sRT should be resorted to in patients with unfavourable loco-regional factors but a low Gleason score.

Written by: Oktay Özman, MD, Urologist, Fellow in Urooncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Netherlands

References:

  1. Cornford P, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. Eur Urol. 2021 Feb;79(2):263-282. doi: 10.1016/j.eururo.2020.09.046. Epub 2020 Oct 7. PMID: 33039206.
  2. Preisser F, Chun FKH, Pompe RS, Heinze A, Salomon G, Graefen M, Huland H, Tilki D. Persistent Prostate-Specific Antigen After Radical Prostatectomy and Its Impact on Oncologic Outcomes. Eur Urol. 2019 Jul;76(1):106-114.
  3. Ray J, Haughey C, Hoey C, et al. miR-191 promotes radiation resistance of prostate cancer through interaction with RXRA. Cancer Lett. 2020 Mar 31;473:107-117.
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