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BackgroundDue to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed therapy (MDT). There are two types of radiation based MDT applied when treating oligometastatic disease: (1) stereotactic body radiation therapy (SBRT) generally used for bone metastases; or (2) SBRT for isolated nodal oligometastases combined with prophylactic elective nodal radiotherapy. This review aims to summarize current evidence data, which may shed light on the optimal management of this heterogeneous group of patients.MethodsA systematic review of the Medline database through PubMed was performed according to PRISMA guidelines. All relevant studies published up to November 2020 were identified and screened. Fifty-six titles were included. Besides outcome parameters, different prognostic and predictive factors were assessed, including site of metastases, time between primary treatment and MDT, use of systemic therapies, hormone sensitivity, as well as pattern of recurrence.FindingsEvidence consists largely of retrospective case series and no consistent precise definition of oligometastasis exists, however, most investigators seem to acknowledge the need to distinguish between patients presenting with what is frequently called "synchronous" versus "metachronous" oligometastatic disease. Available data on radiotherapy as MDT demonstrate high local control rates and a small but relevant proportion of patients without progressive disease after 2 years. This holds true for both hormone sensitive and castration resistant prostate cancer diseases. The use of 68Ga-PSMA PET/CT for staging increased dramatically. Radiation doses and field sizes varied considerably among the studies. The search for relevant prognostic and predictive factors is ongoing.ConclusionsTo our best knowledge this review on oligometastatic prostate cancer included the largest number of original articles. It demonstrates the therapeutic potential and challenges of MDT for oligometastatic prostate cancer. Prospective studies are under way and will provide further high-level evidence.

Purpose or Objective: To provide a comprehensive recurrence and toxicity analysis of patients treated with radiotherapy alone for stage I/II (Ann‐Arbor classification) indolent orbital lymphoma. Material and Methods: We retrospectively reviewed the medical charts of 46 patients (and 51 orbits) treated at our centre with radiotherapy between 1995 and 2012 for biopsy‐proven stage I/IIE primary orbital lymphomas. We evaluated treatment response and performed a comprehensive toxicity analysis with correlation to delivered radiation dose. Results: At diagnosis, the median age was 63.5 years (range: 20–92). At initial diagnosis 43 and 3 patients had unilateral, synchronous bilateral involvement while there were 2 cases of contralateral metachronous failure. The predominant histological subtype was extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue in 42 (91.3%), follicular in 1 (2.2%), lymphoplasmacytic lymphoma in 1 (2.2%) and other indolent histology in 2 (4.3%) patients. Most lymphomas were located in the conjunctiva (18/35.3%) or eyelids (18/35.3%). Thirty‐eight (82.6%) patients presented with stage I while 8/46 (17.4%) with stage II disease. The median radiation dose was 39.6 Gy (range: 21.6–48.6 Gy) delivered in 1.8–2 Gy single fractions. At a median follow‐up of 83 months (range: 7–258 months), the complete remission rate was 98%. A local relapse was observed in 2/51 (3.9%) orbits and 4/46 (8.7%) patients had systemic relapse. The 5‐ and 10‐year PFS rates were 79.2% (95% CI: 73.0%–85.4%) and 67.6% (95% CI: 59.4%–75.8%); 5‐ and 10‐year OS was 83.6% (95% CI: 77.9%–89.3%) and 76.5% (95% CI: 69.4%–83.6%), respectively. In total, 66 acute toxicity events (all‐grade) were observed: 5/51 (9.8%) ≥G2 acute conjunctivitis, 2/51 (3.9%) cases of G2 acute keratitis, 1/51 (2%) cases of ≥G2 ophthalmagia and 12/51 (23.5%) cases of ≥G2 xerophthalmia. Furthermore, 45 chronic adverse events were observed in 34/51 (66.7%) irradiated orbits with 30 late adverse events attributed to cataract. Conclusion: Our analysis confirms the role of radiotherapy alone at lower doses in the treatment of indolent orbital lymphomas. Further research is required to assess the efficacy of ultra‐low‐dose radiotherapy and anti‐CD20 monoclonal antibodies to further mitigate long‐term sequelae. [ABSTRACT FROM AUTHOR]

Purpose: Nodal recurrent prostate cancer (PCa) represents a common state of disease, amenable to local therapy. PSMA-PET/CT detects PCa recurrence at low PSA levels. The aim of this study was to evaluate the outcome of PSMA-PET/CT-based salvage radiotherapy (sRT) for lymph node (LN) recurrence. Methods: A total of 100 consecutive patients treated with PSMA-PET/CT-based salvage elective nodal radiotherapy (sENRT) for LN recurrence were retrospectively examined. Patients underwent PSMA-PET/CT scan due to biochemical persistence (bcP, 76%) or biochemical recurrence (bcR, 24%) after radical prostatectomy (RP). Biochemical recurrence-free survival (BRFS) defined as PSA < post-RT nadir + 0.2 ng/ml and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method and uni- and multivariate analysis was performed. Results: Median follow-up was 37 months. Median PSA at PSMA-PET/CT was 1.7 ng/ml (range 0.1–40.1) in patients with bcP and 1.4 ng/ml (range 0.3–5.1) in patients with bcR. PSMA-PET/CT detected 1, 2, and 3 or more LN metastases in 35%, 23%, and 42%, respectively. Eighty-three percent had only pelvic, 2% had only paraaortic, and 15% had pelvic and paraaortic LN metastases. Cumulatively, a total dose converted to EQD21.5 Gy of 66 Gy (60–70 Gy) was delivered to the prostatic fossa, 70 Gy (66–72 Gy) to the local recurrence, if present, 65.1 Gy (56–66 Gy) to PET-positive lymph nodes, and 47.5 Gy (42.4–50.9 Gy) to the lymphatic pathways. Concomitant androgen deprivation therapy (ADT) was administered in 83% of patients. One-, 2-, and 3-year BRFS was 80.7%, 71.6%, and 65.8%, respectively. One-, 2-, and 3-year DMFS was 91.6%, 79.1%, and 66.4%, respectively. In multivariate analysis, concomitant ADT, longer ADT duration (≥ 12 vs. < 12 months) and LN localization (pelvic vs. paraaortic) were associated with improved BRFS and concomitant ADT and lower PSA value before sRT (< 1 vs. > 1 ng/ml) with improved DMFS, respectively. No such association was seen for the number of affected lymph nodes. Conclusions: Overall, the present analysis shows that the so far, unmatched sensitivity and specificity of PSMA-PET/CT translates in comparably high BRFS and DMFS after PSMA-PET/CT-based sENRT for patients with PCa LN recurrence. Concomitant ADT, duration of ADT, PSA value before sRT, and localization of LN metastases were significant factors for improved outcome. [ABSTRACT FROM AUTHOR]

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Purpose: The optimal timing of radiotherapy (RT) after radical prostatectomy (RP) remains controversial with unknown impact on health-related quality of life (HRQOL). We aimed to compare the influence of early RT (eRT) and deferred RT (dRT) on HRQOL. Materials and Methods: A total of 4,511 patients were analyzed. Inclusion criteria encompassed: ≥pT3, International Society of Urological Pathology grade ≥4, or positive surgical margin. A 1:4 propensity score-matched-analysis of 1,599 patients was conducted (307: eRT, -6 months after RP; 1,292: dRT, >6 months after RP). Primary end point was general HRQOL (based on European Organisation for Research and Treatment of Cancer QLQ-C30). Pearson correlation and binary logistic regression models were used to estimate the impact of timing of RT on HRQOL. Functional outcome was assessed using the International Consultation on Incontinence Questionnaire, short form (ICIQ-SF) and International Index of Erectile Function (IIEF-5) questionnaires. Results: Median followup was 38 months. At 12 months and 24 months followup, general HRQOL scores were significantly higher for dRT (52.7 vs 35.5; p[0.001; 45.8 vs 37.3; p[0.026). ICIQ-SF scores were higher (8.5 vs 6.1; p[0.001; 8.4 vs 7.3; p[0.038), and IIEF-5 scores were lower (1.8 vs 4.2; p[0.001; 2.2 vs 4.4; p[0.005) for eRT at 12 months and 24 months. On multivariate-analysis, dRT was associated with superior general HRQOL at 12 months (OR 0.59, 95% CI 0.37e0.94, p[0.027) and 24 months (OR 0.64, 95% CI 0.39e0.99, p[0.043), respectively. A longer time interval between RP and RT was associated with improved general HRQOL (OR 1.09, 95% CI 1.038e1.143; p <0.001). Conclusions: dRT yields improved short-term HRQOL compared to eRT. Since longer time intervals between RP and RT predict better short-term HRQOL, our data provide further support for the concept of deferred RT at low prostate specific antigen recurrence. [ABSTRACT FROM AUTHOR]

Introduction: 68Ga-PSMA PET/CT is associated with unprecedented sensitivity for localization of biochemically recurrent prostate cancer at low PSA levels prior to radiotherapy. Aim of the present analysis is to examine whether patients undergoing postoperative, salvage radiotherapy (sRT) of the prostatic fossa with no known nodal or distant metastases on conventional imaging (CT and/or MRI) and on positron emission tomography/computed tomography (68Ga-PSMA PET/CT) will have an improved biochemical recurrence-free survival (BRFS) compared to patients with no known nodal or distant metastases on conventional imaging only. Material and Methods: This retrospective analysis is based on 459 patients (95 with and 364 without 68Ga-PSMA PET/CT). BRFS (PSA < post-sRT Nadir + 0.2 ng/ml) was the primary study endpoint. This was first analysed by Kaplan-Meier and uni- and multivariate Cox regression analysis for the entire cohort and then again after matched-pair analysis using tumor stage, Gleason score, PSA at time of sRT and radiation dose as matching parameters. Results: Median follow-up was 77.5 months for patients without and 33 months for patients with 68Ga-PSMA PET/CT. For the entire cohort, tumor stage (pT2 vs. pT3-4; p= <0.001), Gleason score (GS ≤ 7 vs. GS8-10; p=0.003), pre-sRT PSA (<0.5 vs. ≥0.5ng/ml; p<0.001) and sRT dose (<70 vs. ≥70Gy; p<0.001) were the only factors significantly associated with improved BRFS. This was not seen for the use of 68Ga-PSMA PET/CT prior to sRT (p=0.789). Matched-pair analysis consisted of 95 pairs of PCa patients with or without PET/CT and no significant difference in BRFS based on the use of PET/CT was evident (p=0.884). Conclusion: This analysis did not show an improvement in BRFS using 68Ga-PSMA PET/CT prior to sRT neither for the entire cohort nor after matched-pair analysis after excluding patients with PET-positive lymph node or distant metastases a priori. As no improved BRFS resulted with implementation of 68Ga-PSMA PET in sRT planning, sRT should not be deferred until the best "diagnostic window" for 68Ga-PSMA PET/CT. [ABSTRACT FROM AUTHOR]

In the article, the authors present their study on the potential clinical pathway for treatment in inoperable node-positive stage III non-small cell lung cancer (NSCLC) patients with poor prognostic factors and limited pulmonary reserve. Other topics are the standard of care for said patients like concurrent platinum-based chemoradiation (CRT), and the use of positron emission tomography/computed tomography (PET/CT)-based moderate-hypofractionated radiotherapy in said patients.

Background: In case of oligo-recurrent prostate cancer (PC) following prostatectomy, 68Ga-PSMA-PET/CT can be used to detect a specific site of recurrence and to initiate metastasis-directed radiation therapy (MDT). However, large heterogeneities exist concerning doses, treatment fields and radiation techniques, with some studies reporting focal radiotherapy (RT) to PSMA-PET/CT positive lesions only and other studies using elective RT strategies. We aimed to compare oncological outcomes and toxicity between PET/CT-directed RT (PDRT) and PDRT plus elective RT (eRT; i.e. prostate bed, pelvic or paraaortal nodes) in a large retrospective multicenter study. Methods: Data of 394 patients with oligo-recurrent 68Ga-PSMA-PET/CT-positive PC treated between 04/2013 and 01/2018 in six different academic institutions were evaluated. Primary endpoint was biochemical-recurrence-free survival (bRFS). bRFS was analyzed using Kaplan–Meier survival curves and log rank testing. Uni- and multivariate analyses were performed to determine influence of treatment parameters. Results: In 204 patients (51.8%) RT was directed only to lesions seen on 68Ga-PSMA-PET/CT (PDRT), 190 patients (48.2%) received PDRT plus eRT. PDRT plus eRT was associated with a significantly improved 3-year bRFS compared to PDRT alone (53 vs. 37%; p = 0.001) and remained an independent factor in multivariate analysis (p = 0.006, HR 0.29, 95% CI 0.12–0.68). This effect was more pronounced in the subgroup of patients who were treated with PDRT and elective prostate bed radiotherapy (ePBRT) with a 3-year bRFS of 61% versus 22% (p <0.001). Acute and late toxicity grade ≥3 was 0.8% and 3% after PDRT plus eRT versus no toxicity grade ≥3 after PDRT alone. Conclusions: In this large cohort of patients with oligo-recurrent prostate cancer, elective irradiation of the pelvic lymphatics and the prostatic bed significantly improved bRFS when added to 68Ga-PSMA-PET/CT-guided focal radiotherapy. These findings need to be evaluated in a randomized controlled trial. [ABSTRACT FROM AUTHOR]

Background: To determine the potential role of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in radiotherapy (RT) planning for prostate cancer (PCa).Methods: One hundred twenty-nine patients (pts) with 68Ga-PSMA PET/CT were retrospectively analysed. Potentially influencing factors (androgen deprivation therapy, amount of 68Ga-PSMA-HBED-CC, PSA doubling time ≤/> 10 months, PSA before PET/CT, T-/N-category and Gleason score) were evaluated by logistic regression analysis. The detection rate of PSMA PET/CT was compared to contrast enhanced CT and its impact on RT management analysed.Results: One hundred twenty-nine patients (pts) (20 at initial diagnosis, 49 with PSA relapse and 60 with PSA persistence after radical prostatectomy) received PSMA PET/CT prior to RT. The majority of pts. (71.3%) had PET-positive findings (55.1% of pts. with PSA recurrence, 75% of pts. with PSA persistence and 100% of newly diagnosed pts). Median PSA before PET/CT in pts. with pathological findings (n = 92) was 1.90 ng/ml and without (n = 37) 0.30 ng/ml. PSA level at time of PET/CT was the only factor associated with PET-positivity. In pts. with a PSA ≤ 0.2 ng/ml, the detection rate of any lesion was 33.3%, with a PSA of 0.21-0.5 ng/ml 41.2% and with a PSA of 0.51-1.0 ng/ml 69.2%, respectively. Regarding the anatomic distribution of lesions, 42.2% and 14.7% of pts. with relapse or persistence had pelvic lymph node and distant metastases. In pts. at initial diagnosis the detection rate of pelvic lymph nodes and distant metastases was 20% and 10%. 68Ga-PSMA PET/CT had a high detection rate of PCa recurrence outside the prostatic fossa in pts. being considered for salvage RT (22.4% PET-positive pelvic lymph nodes and 4.1% distant metastases). Compared to CT, PSMA PET/CT had a significantly higher sensitivity in diagnosing rates of local recurrence/primary tumour (10.1% vs. 38%), lymph nodes (15.5% vs. 38.8%) and distant metastases (5.4% vs. 14.0%). This resulted in a modification of RT treatment in 56.6% of pts.Conclusions: The detection of PCa is strongly associated with PSA level at time of 68Ga-PSMA PET/CT. PSMA PET/CT differentiates between local, regional and distant metastatic disease with implications for disease management. PSMA PET/CT allows for tumour detection in post-prostatectomy pts. with PSA ≤ 0.5 ng/ml considered for salvage RT. [ABSTRACT FROM AUTHOR]

• ESTRO/ACROP recommendations for the use of androgen deprivation therapy in the various indications of external-beam radiotherapy. • Highlights use of androgen deprivation therapy in the primary as well as postoperative setting of radiotherapy. • Androgen deprivation therapy use during moderate or extremely hypofractionated radiotherapy also addressed. There is no consensus concerning the appropriate use of androgen deprivation therapy (ADT) during primary and postoperative external-beam radiotherapy (EBRT) in the management of prostate cancer (PCa). Thus, the European Society for Radiotherapy and Oncology (ESTRO) Advisory Committee for Radiation Oncology Practice (ACROP) guidelines seeks to present current recommendations for the clinical use of ADT in the various indications of EBRT. A literature search was conducted in MEDLINE PubMed that evaluated EBRT and ADT in prostate cancer. The search focused on randomized, Phase II and III trials published in English from January 2000 to May 2022. In case topics were addressed in the absence of Phase II or III trials, recommendations were labelled accordingly based on the limited body of evidence. Localized PCa was classified according to D'Amico et al. classification in low-, intermediate and high risk PCa. The ACROP clinical committee identified 13 European experts who discussed and analyzed the body of evidence concerning the use of ADT with EBRT for prostate cancer. Key issues were identified and are discussed: It was concluded that no additional ADT is recommended for low-risk prostate cancer patients, whereas for intermediate- and high-risk patients four to six months and two to three years of ADT are recommended. Likewise, patients with locally advanced prostate cancer are recommended to receive ADT for two to three years and when ≥ 2 high-risk factors (cT3-4, ISUP grade ≥ 4 or PSA ≥ 40 ng/ml) or cN1 is present ADT for three years plus additional Abiraterone for two years is recommended. For postoperative patients no ADT is recommended for adjuvant EBRT in pN0 patients whereas for pN1 patients adjuvant EBRT with long-term ADT is performed for at least 24 to 36 months. In the setting of salvage EBRT ADT is performed in biochemically persistent PCa patients with no evidence of metastatic disease. Long-term ADT (24 months) is recommended in pN0 patients with high risk of further progression (PSA ≥ 0.7 ng/ml and ISUP grade group ≥ 4) and a life expectancy of over ten years, whereas short-term ADT (6 months) is recommended in pN0 patients with lower risk profile (PSA < 0.7 ng/ml and ISUP grade group 4). Patients considered for ultra-hypofractionated EBRT as well as patients with image based local recurrence within the prostatic fossa or lymph node recurrence should participate in appropriate clinical trials evaluating the role of additional ADT. These ESTRO-ACROP recommendations are evidence-based and relevant to the use of ADT in combination with EBRT in PCa for the most common clinical settings. [ABSTRACT FROM AUTHOR]

Simple Summary: In this bi-institutional analysis including 421 patients, we report an overall high biochemical-recurrence free survival rate (58% after three years) after positron-emission tomography (PET)-based salvage radiotherapy (sRT). Additionally, the strong prognostic effect of prostate specific antigen (PSA) level prior to sRT in this patient cohort was observed in multivariate regression analyses. Finally, patients who received staging with two different PET tracers for sRT guidance (cholin vs. prostate specific membrane antigen (PSMA) PET) were compared via propensity score matching and no significant differences in biochemical-recurrent free survival BRFS between the two tracers were observed. The purpose of this analysis was primarily to analyze biochemical-recurrence free survival (BRFS) after positron emission tomography (PET)-guided salvage radiotherapy (sRT) in a large cohort, and to further compare BRFS after PSMA vs. choline PET/ computer tomography (CT)-based sRT. This retrospective analysis is based on 421 patients referred for PSMA or choline PET/CT after radical prostatectomy due to biochemically recurrent or persistent disease. BRFS (PSA: 0.2 ng/mL) was defined as the study endpoint. Cox regression analyses were performed to assess the impact of different clinical parameters on BRFS. Additionally, propensity score matching was performed to adjust patient cohorts (PSMA vs. choline PET/CT-based sRT). The median follow-up time was 30 months. BRFS at three years after sRT was 58%. In the multivariate analysis, only PSA before PET imaging and PSA before sRT were significantly associated with BRFS (p < 0.05). After propensity score matching, 272 patients were further analyzed; there was no significant difference in three-year BRFS between patients with PSMA PET-based vs. choline PET-based sRT (55% vs. 63%, p = 0.197). The present analysis confirmed the overall high BRFS rates after PET-based sRT and the strong prognostic effect of PSA level prior to sRT. PSMA PET-based sRT did not have superior BRFS rates when compared with choline PET-based sRT. [ABSTRACT FROM AUTHOR]