PURPOSE OF REVIEW: To summarize recent evidence on the role of radiotherapy in managing pelvic lymph node (PLN) recurrence following curative-intent primary therapy for prostate cancer (PCa), focusing on radiotherapy strategies, novel medical imaging, and oncological outcomes. RECENT FINDINGS: Prostate-specific membrane antigen PET (PSMA-PET) has improved accuracy of staging in patients with PCa; however, more often than not, it fails to correctly identify PLN metastases, and the impact on clinical outcomes of the patients is uncertain. Metastasis-directed therapies (MDT) combined with short-term androgen-deprivation therapy (ADT) in patients with PLN recurrence are associated with a significantly higher risk of recurrence compared to more comprehensive approaches. Emerging data support the role of elective nodal radiotherapy (ENRT) combined with short-term androgen deprivation therapy (ADT) and radiotherapy boost to the PLN metastases to enhance disease control. Notably, despite treating a more extensive pelvic region than MDT, ENRT does not appear to significantly increase acute toxicity or negatively impact quality of life (QoL). Recent evidence suggests a role for androgen receptor pathway inhibitors (ARPI), such as enzalutamide, in patients with high-risk biochemical recurrence, introducing a new treatment paradigm for patients ineligible for salvage radiotherapy. Ongoing prospective studies are refining the role of radiotherapy in combination with systemic treatments. SUMMARY: Despite PSMA-PET allowing for improved staging and better patient-tailored decisions, patients with PLN recurrence continue to benefit from comprehensive multimodal treatment approach. Elective PLN irradiation combined with radiotherapy boost and ADT lead to improved disease control, without compromising safety and toxicity. ARPI+ADT and ARPI-monotherapy emerge as alternatives for select patients.

• Keywords
• PET, local, neoplasm recurrence, pelvic radiotherapy, prostatic neoplasm, salvage therapy,
• MeSH
• Androgen Antagonists therapeutic use   MeSH
• Quality of Life MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * radiotherapy   MeSH
• Lymphatic Metastasis radiotherapy   MeSH
• Lymph Nodes * pathology   radiation effects   diagnostic imaging   MeSH
• Prostatic Neoplasms * pathology   therapy   radiotherapy   MeSH
• Lymphatic Irradiation * adverse effects   methods   MeSH
• Pelvis MeSH
• Neoplasm Staging MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Androgen Antagonists MeSH

PURPOSE OF REVIEW: We aimed to summarize the recent advancements in management of biochemical recurrence (BCR) after primary curative therapy for prostate cancer (PCa), and the role of advanced imaging technologies in guiding and improving treatment decisions. RECENT FINDINGS: Recent studies have reshaped the approach to managing BCR after primary treatment for PCa. A key shift is the preference for early salvage radiotherapy (sRT), which has proven to offer comparable or even superior outcomes to immediate adjuvant therapy when closely monitored for progression. PSA kinetics (PSA doubling time) continue to guide treatment decisions, together with the time to PSA rise, Gleason Grade of the original tumor, and PSMA-PET imaging at the time of recurrence. While PSMA-PET significantly enhances the precision of recurrence detection, its sensitivity for smaller pelvic lymph node metastases remains limited, underscoring the need for careful consideration of all factors together to develop a risk-based consulting for all individualized treatment plan integrating patient wishes and health. SUMMARY: Recent studies underscore the efficacy of early sRT in managing BCR, with PSA kinetics and ISUP score as a crucial factor in guiding treatment decisions. Furthermore, the integration of PSMA-PET imaging has improved the precision of recurrence detection, facilitating more tailored and effective treatment strategies for patients with BCR. We are finally entering the age of personalized, risk-based, patient-centred case delivery, where treatment of the primary tumor with curative intent is offered to patients with BCR.

• Keywords
• PSMA-PET, biochemical recurrence, prostate cancer, salvage therapy,
• MeSH
• Radiotherapy, Adjuvant MeSH
• Risk Assessment MeSH
• Clinical Decision-Making MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * therapy   blood   diagnosis   MeSH
• Prostatic Neoplasms * therapy   blood   pathology   diagnostic imaging   MeSH
• Positron-Emission Tomography MeSH
• Prostatectomy MeSH
• Prostate-Specific Antigen blood   MeSH
• Neoplasm Grading MeSH
• Treatment Outcome MeSH
• Salvage Therapy * methods   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Prostate-Specific Antigen MeSH

PURPOSE: [18F] Poly-ADP-ribose polymerase inhibitors (PARPi), a novel radiotracer, enables visualization of PARP1 upregulation by PET imaging. Here, we aimed to quantify PARPi uptake in tumor lesions of metastatic castration-resistant PCa (mCRPC) patients and perform a comparison with prostate specific membrane antigen (PSMA) expression using PET/CT scans. METHODS: Data from 22 male patients with mCRPC, who underwent [18F]PARPi and [68Ga]Ga-PSMA-11 PET/CT scans, were retrospectively quantified. Lesions with relevant PARPi uptake (higher than background) were delineated and correlated with their [68Ga]PSMA uptake using standardized uptake values (SUV). Additionally, a comparison was performed to investigate the effects of homologous recombination deficiency (HRD) alterations on PARPi tumor uptake. RESULTS: The majority of metastatic PCa lesions that exhibited PARPi uptake were located in the bones (n = 57), with mean SUVmax values of 4.9 ± 1.5 for PARPi and 30.9 ± 28.3 for [68Ga]PSMA. Additionally, 3 local prostate lesions, 14 lymph nodes and 4 further metastatic lesions were detected. Significant correlations were identified between PARPi- and [68Ga]PSMA uptake, as measured by SUVmean (r = 0.48, p < 0.001), SUVpeak (r = 0.48, p < 0.001) and SUVmax (r = 0.43, p < 0.001) of the osseous metastatic lesions and SUVpeak (r = 0.49, p = 0.04) of extraosseous lesions. No significant differences were found between PARPi uptake of metastatic lesions in patients with or without HRD alterations (all p > 0.05). CONCLUSION: Results showed a considerable uptake of [18F]PARPi in mCRPC patients and indicated a correlation between PARPi uptake and PSMA expression, suggesting the potential of using [18F]PARPi as a diagnostic imaging tool in mCRPC patients. More studies are needed to evaluate the clinical benefit of this innovative radiotracer.

• Keywords
• 18F-PARPi, PET/CT, PSMA, Prostate cancer, mCRPC,
• Publication type
• Journal Article MeSH

Prostate cancer remains a leading cause of cancer-related mortality in men, with advanced stages posing significant treatment challenges due to high morbidity and mortality. Among genetic alterations, TP53 mutations are among the most prevalent in cancers and are strongly associated with poor clinical outcomes and therapeutic resistance. This review investigates the role of TP53 mutations in prostate cancer progression, prognosis, and therapeutic development. A comprehensive analysis of preclinical and clinical studies was conducted to elucidate the molecular mechanisms, clinical implications, and potential therapeutic approaches associated with TP53 alterations in prostate cancer. TP53 mutations are highly prevalent in advanced stages, contributing to genomic instability, aggressive tumor phenotypes, and resistance to standard treatments. Emerging evidence supports the utility of liquid biopsy techniques, such as circulating tumor DNA analysis, for detecting TP53 mutations, providing prognostic value and facilitating early intervention strategies. Novel therapeutic approaches targeting TP53 have shown promise in preclinical settings, but their clinical efficacy requires further validation. Overall, TP53 mutations represent a critical biomarker for disease progression and therapeutic response in prostate cancer. Advances in detection methods and targeted therapies hold significant potential to improve outcomes for patients with TP53-mutated prostate cancer. Further research is essential to integrate TP53-based strategies into routine clinical practice.

• Keywords
• TP53 alteration, castration-resistant prostate cancer (CRPC), genetics, metastatic hormone-sensitive prostate cancer (mHSPC), prostate cancer (PCa),
• Publication type
• Journal Article MeSH
• Review MeSH

Between 25% and 33% of patients after radical prostatectomy experience a relapse of the disease. The risk of relapse increases in patients with risk factors up to 50%-80%. For a long time, adjuvant radiotherapy has been considered the standard of care. Four large prospective trials, that compared adjuvant and salvage radiotherapy in patients with biochemical relapse, showed the superiority of the adjuvant approach in biochemical and local relapse-free survival, but no consistent benefit in long-term endpoints (i.e., metastasis-free survival, overall survival, or carcinoma-specific survival) at the expense of increased urinary and bowel toxicity. Three large international studies comparing adjuvant and salvage radiotherapy paved the way toward early salvage radiotherapy. However, the optimal threshold of the PSA level (range of 0.2-0.5 ng/mL) for initiating early salvage radiotherapy remains unresolved and still poses a challenge in everyday clinical practice when balancing the need for early radiotherapy and the associated toxicity. Imprecise stratification of biochemical relaps patients according to the risk of clinical relapse drives efforts to find additional molecular biomarkers that would improve the timing of the salvage therapy.

• Keywords
• biochemical relapse, high risk, prostate cancer, salvage radiotherapy, timing,
• Publication type
• Journal Article MeSH
• Review MeSH

PURPOSE: Hypofractionated radiotherapy for prostate cancer is well established for definitive treatment, but not well defined in the postoperative setting. The purpose of this analysis was to assess oncologic outcomes and toxicity in a large cohort of patients treated with conventionally fractionated three-dimensional (3D) conformal radiotherapy (CF) and hypofractionated volumetric modulated arc therapy (HF) after radical prostatectomy. METHODS: Between 1994 and 2019, a total of 855 patients with prostate carcinoma were treated by postoperative radiotherapy using CF (total dose 65-72 Gy, single fraction 1.8-2 Gy) in 572 patients and HF (total dose 62.5-63.75 Gy, single fraction 2.5-2.55 Gy) in 283 patients. The association of treatment modality with biochemical control, overall survival (OS), and gastrointestinal (GI) and genitourinary (GU) toxicity was assessed using logistic and Cox regression analysis. RESULTS: There was no difference between the two modalities regarding biochemical control rates (77% versus 81%, respectively, for HF and CF at 24 months and 58% and 64% at 60 months; p = 0.20). OS estimates after 5 years: 95% versus 93% (p = 0.72). Patients undergoing HF had less frequent grade 2 or higher acute GI or GU side effects (p = 0.03 and p = 0.005, respectively). There were no differences in late GI side effects between modalities (hazard ratio 0.99). Median follow-up was 23 months for HF and 72 months for CF (p < 0.001). CONCLUSION: For radiation therapy of resected prostate cancer, our analysis of this largest single-centre cohort (n = 283) treated with hypofractionation with advanced treatment techniques compared with conventional fractionation did not yield different outcomes in terms of biochemical control and toxicities. Prospective investigating of HF is merited.

• Keywords
• Biochemical control, Gastrointestinal toxicity, Genitourinary toxicity, Postoperative, bNED,
• MeSH
• Radiation Dose Hypofractionation MeSH
• Humans MeSH
• Prostatic Neoplasms * pathology   radiotherapy   surgery   MeSH
• Prospective Studies MeSH
• Prostate pathology   MeSH
• Prostatectomy MeSH
• Radiotherapy, Intensity-Modulated * methods   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

PURPOSE: To examine the predictive and prognostic value of preoperative Systemic Immune-inflammation Index (SII) in patients with radio-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP). MATERIALS AND METHODS: This multicenter retrospective study included 214 patients with radio-recurrent PCa, treated with SRP between 2007 and 2015. SII was measured preoperatively (neutrophils × platelets/lymphocytes) and the cohort was stratified using optimal cut-off. Uni- and multivariable logistic and Cox regression analyses were performed to evaluate the predictive and prognostic value of SII as a preoperative biomarker. RESULTS: A total of 81 patients had high preoperative SII (≥ 730). On multivariable logistic regression modeling, high SII was predictive for lymph node metastases (OR 3.32, 95% CI 1.45-7.90, p = 0.005), and non-organ confined disease (OR 2.55, 95% CI 1.33-4.97, p = 0.005). In preoperative regression analysis, high preoperative SII was an independent prognostic factor for cancer-specific survival (CSS; HR 10.7, 95% CI 1.12-103, p = 0.039) and overall survival (OS; HR 8.57, 95% CI 2.70-27.2, p < 0.001). Similarly, in postoperative multivariable models, SII was associated with worse CSS (HR 22.11, 95% CI 1.23-398.12, p = 0.036) and OS (HR 5.98, 95% CI 1.67-21.44, p = 0.006). Notably, the addition of SII to preoperative reference models improved the C-index for the prognosis of CSS (89.5 vs. 80.5) and OS (85.1 vs 77.1). CONCLUSIONS: In radio-recurrent PCa patients, high SII was associated with adverse pathological features at SRP and survival after SRP. Preoperative SII could help identify patients who might benefit from novel imaging modalities, multimodal therapy or a closer posttreatment surveillance.

• Keywords
• Biomarkers, Prostate cancer, SII, Salvage radical prostatectomy, Survival,
• MeSH
• Brachytherapy MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local immunology   mortality   pathology   surgery   MeSH
• Lymph Nodes pathology   MeSH
• Lymphocytes * MeSH
• Survival Rate MeSH
• Multivariate Analysis MeSH
• Prostatic Neoplasms immunology   mortality   pathology   surgery   MeSH
• Neutrophils * MeSH
• Leukocyte Count MeSH
• Lymphocyte Count MeSH
• Platelet Count MeSH
• Preoperative Period MeSH
• Prognosis MeSH
• Proportional Hazards Models MeSH
• Prostatectomy * MeSH
• Radiotherapy, Intensity-Modulated MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Blood Platelets * MeSH
• Salvage Therapy * MeSH
• Inflammation blood   immunology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH

PURPOSE: To examine the effect of lymph node dissection on the outcomes of patients who underwent salvage radical prostatectomy (SRP). MATERIAL AND METHODS: We retrospectively reviewed data from radiation-recurrent patients with prostate cancer (PCa) who underwent SRP from 2000-2016. None of the patients had clinical lymph node involvement before SRP. The effect of the number of removed lymph nodes (RLNs) and the number of positive lymph nodes (PLNs) on biochemical recurrence (BCR)-free survival, metastases free survival, and overall survival (OS) was tested in multivariable Cox regression analyses. RESULTS: About 334 patients underwent SRP and pelvic lymph node dissection (PLND). Lymph node involvement was associated with increased risk of BCR (p < .001), metastasis (p < .001), and overall mortality (p = .006). In a multivariable Cox regression analysis, an increased number of RLNs significantly lowered the risk of BCR (hazard ratio [HR] 0.96, p = .01). In patients with positive lymph nodes, a higher number of RLNs and a lower number of PLNs were associated with improved freedom from BCR (HR 0.89, p = .001 and HR 1.34, p = .008, respectively). At a median follow-up of 23.9 months (interquartile range, 4.7-37.7), neither the number of RLNs nor the number of PLNs were associated with OS (p = .69 and p = .34, respectively). CONCLUSION: Pathologic lymph node involvement increased the risk of BCR, metastasis and overall mortality in radiation-recurrent PCa patients undergoing SRP. The risk of BCR decreased steadily with a higher number of RLNs during SRP. Further research is needed to support this conclusion and develop a precise therapeutic adjuvant strategy based on the number of RLNs and PLNs.

• Keywords
• BCR, localized, lymphadenectomy, metastasis,
• Publication type
• Journal Article MeSH