The findings of this study show that GS 10 PCa is highly aggressive, as evidenced by a recurrence rate of more than 40% among patients, particularly in the form of DM, emphasizing the importance of implementing effective treatment strategies and appropriate staging. The use of long-term ADT had a significant positive impact on all treatment outcome parameters, while the use of 68Ga-PSMA-PET/CT for staging resulted in a significant improvement in FFBF and PCSS. Moreover, implementation of the SIB technique resulted in a significant improvement in FFBF and DMFS, while not leading to a statistically significant increase in acute or late GI and GU toxicities.

The optimal management strategies and treatment outcomes for GS 10 PCa are not well established due to its rarity. Recent database trials involving a substantial number of GS 9 and 10 cancers have shown that both RT and RP yield similar treatment results [14,15,16]. However, the proportion of GS 10 PCa patients in these studies was less than 10% of the study cohort. Previous studies demonstrated differences in mortality between patients with biopsied GS 9 and 10 PCa treated with RP or external beam radiation therapy (EBRT), with the highest mortality observed in GS 10 PCa patients [2, 22]. Only a few studies have evaluated the outcomes of patients with GS 10 PCa treated with different modalities [17,18,19]. Mai et al. [18] found that the 5‑year DMFS, PCSS, and OS rates were 57%, 67%, and 57%, respectively, for 9 patients who underwent EBRT and long-term ADT. Inman et al. [17] conducted an analysis of 13 patients who had pathologically confirmed GS 10 disease after RP. They found that the 5‑year PCSS and OS rates were 77% and 66%, respectively. Sandler et al. [19] found that aggressive therapy with curative intent is warranted, as more than half of 112 GS 10 PCa patients treated with RP (26 patients), EBRT (48 patients), and EBRT with brachytherapy (BT) boost (38 patients) remained free of systemic disease 5 years after treatment. The current study confirms previous findings, despite nearly half of the patients having nodal metastases, a risk factor for poor survival. Several factors contribute to this result, such as the use of 68Ga-PSMA-PET/CT for staging in over 50% of patients, the implementation of pelvic lymph node RT, the application of a higher radiation dose, and the use of ADT in all patients.

Recent developments in imaging techniques have greatly enhanced the ability to detect DM, leading to improved clinical staging [12]. Moreover, 68Ga-PSMA-PET/CT is frequently used for RT planning in high-risk PCa patients. Multiple studies have demonstrated that the outcomes of 68Ga-PSMA-PET/CT often have a significant impact on the course of local RT [23, 24]. Approximately 60% of patients in the present study underwent 68Ga-PSMA-PET/CT for staging upon initial diagnosis, and the results obtained from 68Ga-PSMA-PET/CT were used to determine the RT plan. Furthermore, the findings of the univariate analysis indicated that the use of 68Ga-PSMA-PET/CT had a significant impact on both FFBF and PCSS. This can be attributed to the improved identification of DM during the initial diagnosis, thereby enabling effective treatment interventions. In addition, the multivariable analysis demonstrated a significant correlation between 68Ga-PSMA-PET/CT staging and improved FFBF outcomes, highlighting the significance of accurate staging.

The survival benefit of dose escalation, either through the SIB technique or BT boost, has been demonstrated in recent randomized trials for patients with intermediate- and high-risk PCa [7, 8]. In addition, recent database trials have shown that BT boost to EBRT yields better results compared to EBRT alone or RP in patients with GS 9–10 PCa. [14, 16, 22, 25, 26]. Finally, Sandler et al. [19] reported 5‑year PCSS rates of 87%, 75%, and 94% for RP, EBRT, and EBRT with BT boost groups, respectively, in GS 10 PCa patients. The 5‑year DMFS rates for the RP, EBRT, and EBRT-BT groups were 64%, 62%, and 87%, respectively. Our findings align with those of previous research [19], highlighting the significant improvement in patient outcomes when applying dose escalation with the SIB technique. This emphasizes the importance of local control for reducing DM and PCa mortality in this specific patient population.

Recent randomized trials have shown the advantages of long-term ADT in comparison to short-term ADT or no ADT in high-risk PCa patients [6, 27, 28]. The MARCAP consortium has shown that the advantages of incorporating or extending ADT in the treatment of localized PCa with RT outweigh the benefits of escalating the RT dose [5, 11]. The results of this study also show the survival advantage of long-term ADT compared to ADT with a duration of less than 18 months in a patient population with a relatively high risk. Nevertheless, it is worth noting that patients with GS 10 tumors are at a high risk of developing DM. It is likely that future studies utilizing androgen receptor-targeted agents will provide evidence of the advantages of implementing aggressive hormonal therapy for this specific patient group. The STAMPEDE trial presented findings that support the notion that the use of combination therapy, specifically abiraterone and ADT, is associated with significantly higher rates of metastasis-free survival in patients with high-risk nonmetastatic PCa in comparison to the use of ADT alone [29]. The ENZARAD trial aims to assess the effectiveness of enzalutamide in comparison to non-steroidal anti-androgens with LHRHA in men who are scheduled to undergo RT for localized high-risk or node-positive PCa (ClinicalTrials.gov identifier: NCT 02446444). The ATLAS trial aims to evaluate the impact of combining apalutamide with LHRHA on the survival rates of high-risk PCa patients undergoing primary RT (ClinicalTrials.gov identifier: NCT02531516).

This study has limitations due to its retrospective design and potential selection bias. Our study is limited by a small patient population, and the duration of ADT varied according to clinical practice. In addition, our findings primarily pertain to needle biopsy specimens, which may not accurately reflect the actual Gleason score determined from RP specimens. Finally, our study was conducted at a single institution and would benefit from further validation to ensure a more precise assessment of clinical outcomes. Despite these limitations, this study also offers several advantages. For instance, it boasts a large sample size compared to previous series. Additionally, the study focused on a homogeneous patient population, all of whom underwent ADT and pelvic nodal irradiation with modern RT techniques.