Elective nodal radiotherapy in prostate cancer

In patients with prostate cancer who have a high risk of pelvic nodal disease, the use of elective whole pelvis radiotherapy is still controversial. Two large, randomised, controlled trials (RTOG 9413 and GETUG-01) did not show a benefit of elective whole pelvis radiotherapy over prostate-only radiotherapy. In 2020, the POP-RT trial established the role of elective whole pelvis radiotherapy in patients who have more than a 35% risk of lymph node invasion (known as the Roach formula). POP-RT stressed the importance of patient selection. In patients with cN1 (clinically node positive) disease or pN1 (pathologically node positive) disease, the addition of whole pelvis radiotherapy to androgen deprivation therapy significantly improved survival compared with androgen deprivation therapy alone, as shown in large, retrospective studies. This patient population might increase in the future because use of the more sensitive prostate-specific membrane antigen PET-CT will become the standard staging procedure. Additionally, the SPORTT trial suggested a benefit of whole pelvis radiotherapy in biochemical recurrence-free survival in the salvage setting. A correct definition of the upper field border, which should include the bifurcation of the abdominal aorta, is key in the use of pelvic radiotherapy. As a result of using modern radiotherapy technology, severe late urinary and intestinal toxic effects are rare and do not seem to increase compared with prostate-only radiotherapy

Oligorecurrent nodal prostate cancer: radiotherapy quality assurance of the randomized PEACE V-STORM phase II trial.

PURPOSE Aim of this study is to report the results of the radiotherapy quality assurance program of the PEACE V-STORM randomized phase II trial for pelvic nodal oligorecurrent prostate cancer (PCa). MATERIAL AND METHODS A benchmark case (BC) consisting of a postoperative case with 2 nodal recurrences was used for both stereotactic body radiotherapy (SBRT, 30 Gy/3 fx) and whole pelvic radiotherapy (WPRT, 45 Gy/25 fx + SIB boost to 65 Gy). RESULTS BC of 24 centers were analyzed. The overall grading for delineation variation of the 1st BC was rated as 'UV' (Unacceptable Variation) or 'AV' (Acceptable Variation) for 1 and 7 centers for SBRT (33%), and 3 and 8 centers for WPRT (46%), respectively. An inadequate upper limit of the WPRT CTV (n=2), a missing delineation of the prostate bed (n=1), and a missing nodal target volume (n=1 for SBRT and WPRT) constituted the observed 'UV'. With the 2nd BC (n=11), the overall delineation review showed 2 and 8 'AV' for SBRT and WPRT, respectively, with no 'UV'. For the plan review of the 2nd BC, all treatment plans were per protocol for WPRT. SBRT plans showed variability in dose normalization (Median D90% = 30.1 Gy, range 22.9-33.2Gy and 30.6 Gy, range 26.8-34.2Gy for nodes 1 and 2 respectively). CONCLUSIONS Up to 46% of protocol deviations were observed in delineation of WPRT for nodal oligorecurrent PCa, while dosimetric results of SBRT showed the greatest disparities between centers. Repeated BC resulted in an improved adherence to the protocol, translating in an overall acceptable contouring and planning compliance rate among participating centers

Extended field radiotherapy measurements in a single shot using a BaFBr-based OSL-film

This work evaluated the use of a class solution specific calibration for an extra-large BaFBr-based optically stimulated luminescence film (OSL; 43  ×  35 cm2; Z eff  =  4.55). The clinical need for such large dosimeters follows from the increased use of extended-field radiation therapy (EFRT). E.g. for prostate cancer EFRT is currently used in the first prospective trial investigating the benefit of adding elective irradiation of the para-aortic lymph nodes in pN1 prostate cancer. The full extent of these EFRT dose distributions is not covered by the well-established standard sized radiochromic film or 2D detector arrays. Here we investigate an OSL calibration methodology, that tackles BaFBr-based OSL's inherent energy dependence by a class solution specific calibration. 10 EFRT treatment plans used in the PART trial were investigated. One plan was used to build a class solution specific bilinear calibration model, that distinguishes between in-field and penumbra dose contributions. The effect of this calibration was evaluated with respect to a standard linear calibration, using standard IMRT patterns, the nine remaining patient plans, and to smaller prostate treatment plans. A single OSL-dosimeter could be reused for all measurements. The dosimeter captured the full extent of the dose distributions (maximum EFRT field size  =  33.5 cm). The bilinear correction reduced the residual dose differences from above 10% to an average of 0.7% (max 3.6%) in comparison with a Monte Carlo simulation. Consequently global gamma agreement scores (3%-3 mm) of 95.5%  ±  2.7% were reached. A more strict local evaluation resulted in an average gamma-agreement score of 93.3%  ±  3.2%. The BaFBr-based OSL film, with reduced Z eff requires a class-solution specific correction. The current work shows that such a correction can be as simple as a bilinear residual dose correction driven by the measured signal. As far as we know this is the first 2D dosimeter combining reusability, a sub-mm resolution, and a size covering the typical EFRT treatment plans.status: publishe

The Use of Soy Isoflavones in the Treatment of Prostate Cancer: A Focus on the Cellular Effects

A possible link between diet and cancer has long been considered, with growing interest in phytochemicals. Soy isoflavones have been associated with a reduced risk of prostate cancer in Asian populations. Of the soy isoflavones, genistein and daidzein, in particular, have been studied, but recently, equol as a derivative has gained interest because it is more biologically potent. Different mechanisms of action have already been studied for the different isoflavones in multiple conditions, such as breast, gastrointestinal, and urogenital cancers. Many of these mechanisms of action could also be demonstrated in the prostate, both in vitro and in vivo. This review focuses on the known mechanisms of action at the cellular level and compares them between genistein, daidzein, and equol. These include androgen- and estrogen-mediated pathways, regulation of the cell cycle and cell proliferation, apoptosis, angiogenesis, and metastasis. In addition, antioxidant and anti-inflammatory effects and epigenetics are addressed

Radiotherapie bij primaire prostaatkanker: als minder meer wordt

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Metastasis-directed therapy for oligometastatic urological tumours: still no second-hand news

For patients presenting with limited metastatic disease burden, known as the oligometastatic state of disease, a more aggressive treatment approach targeting the new or progressive metastatic lesions might improve patient outcome, with no or only limited toxicity to be expected from the treatment. This review provides an overview of the existing evidence and on-going trials on oligometastatic disease and metastasis-directed therapy in the field of renal, bladder and prostate cancer.status: publishe

Long- versus short-term androgen deprivation therapy with high-dose radiotherapy for biochemical failure after radical prostatectomy: a randomized controlled trial.

Radical prostatectomy is a well-established treatment option in the management of localized and locally advanced prostate cancer. An extended lymphadenectomy is performed in case of substantial risk for lymph node involvement. When biochemical recurrence (BCR) occurs, salvage radiotherapy (SRT) is performed. The benefit in terms of BCR-free survival (FS) and metastasis-FS by adding 6 months of androgen deprivation therapy (ADT) compared with SRT only has already been established. Retrospective evidence suggests that a longer schedule of ADT may be more beneficial compared with 6 months. This multicenter open-label randomized trial will include patients who need SRT after experiencing BCR post-radical prostatectomy with lymphadenectomy and pN0-status. Patients will be randomized for ADT duration (6 vs 24 months). Primary end point is distant metastasis-FS. Clinical Trial Registration: NCT04242017 (ClinicalTrials.gov).status: publishe

Progression-directed Therapy for Oligoprogression in Castration-refractory Prostate Cancer.

In metastatic castration-refractory prostate cancer (mCRPC), state-of-the-art treatment consists of androgen biosynthesis inhibition (abiraterone), inhibition of the androgen receptor (enzalutamide), chemotherapy, or radium-223 in combination with androgen deprivation therapy (ADT). A subgroup of these patients show oligoprogression, with the progression of only a limited number of metastatic spots, while all other metastases remain controlled by ongoing systemic therapy. In a bi-institutional retrospective study, we tested the hypothesis that progression-directed therapy (PDT) targeting oligoprogressive lesions might defer the initiation of next-line systemic treatment (NEST). A total of 30 patients were diagnosed with mCRPC and experienced oligoprogression, defined as a total of three or fewer progressive lesions either at known metastatic sites and/or the appearance of new metastasis and/or local recurrence. All patients were under active ADT with or without second-line systemic treatment. All patients received PDT targeting the oligoprogressive lesions, while ongoing systemic treatment was maintained. There was median NEST-free survival of 16mo (95% confidence interval [CI] 10-22) and progression-free survival of 10mo (95% CI 6-15) with only minor radiotherapy- or surgery-related toxicity. These findings encourage further prospective trials. PATIENT SUMMARY: In patients with metastatic castration-refractory prostate cancer, surgical treatment or high-dose radiation therapy directed to only the limited number of progressive metastatic spots, while all other metastases remained controlled by ongoing systemic therapy, led to substantial postponement of next-line systemic treatment in our study.status: Published onlin