Multi-institutional Evaluation of Elective Nodal Irradiation and/or Androgen Deprivation Therapy with Postprostatectomy Salvage Radiotherapy for Prostate Cancer

Ramey, Stephen J.; Agrawal, Shree; Abramowitz, Matthew C.; Moghanaki, Drew; Pisansky, Thomas M.; Efstathiou, Jason A.; Michalski, Jeff M.; Spratt, Daniel E.; Hearn, Jason W.D.; Koontz, Bridget F.; Liauw, Stanley L.; Pollack, Alan; Anscher, Mitchell S.; Den, Robert B.; Stephans, Kevin L.; Zietman, Anthony L.; Lee, William R.; Stephenson, Andrew J.; Tendulkar, Rahul D.

doi:10.1016/j.eururo.2017.10.009

Cited by 29 publications

(30 citation statements)

References 37 publications

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“…There is no level 1 evidence to demonstrate superiority in survival benefits in patients receiving WPRT compared with prostate bed irradiation, although WPRT was reported to improve bPFS in some retrospective studies. 17,18 In addition, there is a significant concern of treatment-related toxicities in patients receiving WPRT, especially after pelvic nodal dissection, compared with prostate bed irradiation. Despite these concerns, postoperative WPRT is commonly used to treat patients with prostate cancer with high-risk factors, although the definition of these risk factors varies among institutions.…”

Section: Discussionmentioning

confidence: 99%

Toxicity and Biochemical Outcomes of Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Results of a Randomized Phase III Trial

Gao

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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Purpose: Our purpose was to compare toxicity and biochemical control in postprostatectomy patients treated with conventional (66 Gy) or dose-intensified (72 Gy) radiation therapy. Methods and Materials: Patients who had stage pT3-4, positive surgical margins, or rising prostate-specific antigen 0.2 ng/mL after radical prostatectomy were randomly assigned to receive either 66 Gy in 33 fractions or 72 Gy in 36 fractions. A primary endpoint was to assess the difference in biochemical progression-free survival (bPFS) between these 2 cohorts, and secondary endpoints were to assess differences in genitourinary (GU), gastrointestinal (GI), and hematologic toxicities between these 2 cohorts. bPFS was estimated by the KaplaneMeier method and toxicities were compared using the c 2 test.Results: Between September 2011 and November 2016, 144 patients were enrolled: 71 patients to the 66 Gy cohort and 73 patients to the 72 Gy cohort. The median follow-up time was 48.5 months (range, 14-79 months). There was no difference in 4-year bPFS between the 66 Gy and 72 Gy cohorts (75.9% vs 82.6%; P Z .299). However, in patients with a higher Gleason score (8-10), the 72 Gy cohort had statistically significant improvement in bPFS compared with the 66 Gy cohort (79.7% vs 55.7%; P Z .049). Toxicity analysis showed no difference in 2 acute or late GI or GU toxicities between these 2 cohorts. A total of 48 patients were scored as urinary incontinence before radiation therapy, of which 39 (81.3%) reported incontinence recovery or stable at 1-year follow-up, and only 9 (18.8%) patients reported worsening. There was no difference between the 2 cohorts in urinary incontinence either at baseline or at 1-year follow-up.Conclusions: Dose escalation (72 Gy) demonstrated no improvement in 4-year bPFS compared with the 66 Gy regimen. However, the dose escalation was not associated with greater acute or late GU or GI toxicities and did not increase urinary incontinence. Ó 2019 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Volume 106 Number 2 2020Postoperative RT for prostate cancer 283Abbreviations: ART Z adjuvant radiation therapy; ISUP Z International Society of Urologic Pathology; PSA Z prostate-specific antigen; PUFH Z Peking University First Hospital; RP Z radical prostatectomy; RT Z radiation therapy; SRT Z salvage radiation therapy; WPRT Z whole pelvic radiation therapy. Note: P values were calculated by Mann-Whitney U test or c 2 test where appropriate.

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Section: Discussionmentioning

confidence: 99%

Toxicity and Biochemical Outcomes of Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Results of a Randomized Phase III Trial

Gao

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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“…Several retrospective studies reported that elective pelvic lymph node irradiation (i.e. WPRT) improved biochemical control in selected patients 37,38 . With limited available evidence, WPRT is currently an option for patients with adverse features such as pathological nodal metastasis and Gleason score ≥8 30 .…”

Section: Discussionmentioning

confidence: 99%

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy

Tomita

Uchiyama

Mizuno

et al. 2020

Sci Rep

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The safety and efficacy of dose-escalated radiotherapy with intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) remain unclear in salvage radiotherapy (SRT) after radical prostatectomy. We examined the impact of these advanced radiotherapy techniques and dose intensification on the toxicity of SRT. This multi-institutional retrospective study included 421 patients who underwent SRT at the median dose of 66 Gy in 2-Gy fractions. IMRT and IGRT were used for 225 (53%) and 321 (76%) patients, respectively. At the median follow-up of 50 months, the cumulative incidence of late grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicities was 4.8% and 24%, respectively. Multivariate analysis revealed that the non-use of either IMRT or IGRT, or both (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.8-5.4, p < 0.001) and use of whole-pelvic radiotherapy (HR 7.6, CI 1.0-56, p = 0.048) were associated with late GI toxicity, whereas a higher dose ≥68 Gy was the only factor associated with GU toxicities (HR 3.1, CI 1.3-7.4, p = 0.012). This study suggested that the incidence of GI toxicities can be reduced by IMRT and IGRT in SRT, whereas dose intensification may increase GU toxicity even with these advanced techniques.Prostate cancer patients with biochemical recurrence (BCR) after radical prostatectomy (RP) have a risk of metastasis and cancer death 1 . Approximately 30% of patients with an adverse feature, such as high Gleason score, develop BCR after RP 2 . Salvage radiotherapy (SRT) is the only curative option for these patients 3,4 . The target volume of SRT is the prostate bed with or without the seminal vesicle 5 , which is situated precisely between the bladder and rectum. In a dosimetric study using consensus guidelines for target volume delineations of SRT, intensity-modulated radiation therapy (IMRT) enabled dose increase within acceptable dose constraints of the organs at risk (OARs) such as the bladder and rectum 6 . Regarding definitive radiotherapy (RT) without RP, the ratio of IMRT markedly increased in the 2000s 7 due to benefits of high-dose prescription 8 . As systematic reviews and meta-analyses revealed that dose escalation improved biochemical control even in SRT 9,10 , dose escalation with IMRT has been employed for patients with BCR after RP [11][12][13] . However, dose-escalated RT, even with the IMRT technique, may increase toxicity. Image-guided radiation therapy (IGRT) enables more accurate setup by computed tomography (CT) immediately before treatment. IGRT is also one of the recent advanced RT techniques, as is IMRT, and is used more commonly with IMRT. However, the safety and efficacy of dose-escalated RT with IMRT and IGRT remain unclear. In addition, whether IMRT and IGRT reduce toxicity in SRT is still unknown. Thus, we examined the impact of advanced RT techniques and dose intensification on the toxicity of SRT after RP. Methods patient selection. We identified 421 patients who received SRT for BCR after RP between 2005 and 2017 at 15 institutions....

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“…Ramey et al showed that adding whole pelvic radiation therapy had a potential to suppress relapse again. 23 New diagnostic techniques such as 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA-11) positron emission/computed tomography (CT) may enable detection of micrometastases that have been difficult to find, and this may have an impact on the selection of treatment methods for salvage therapy including SBRT. 24 …”

Section: Prostate Cancermentioning

confidence: 99%

Stereotactic Radiotherapy for Oligometastases in Lymph Nodes—A Review

Matsushita

Jingu

Umezawa

et al. 2018

Technol Cancer Res Treat

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In recent years, the concept of oligometastases has become accepted and reports on stereotactic body radiotherapy as a treatment method have been published. Lesions in the brain, lung, and liver have been reported as target lesions. However, lymph node oligometastases could be a good candidate for stereotactic body radiotherapy as well. In this study, the usability of stereotactic body radiotherapy for oligometastases to lymph nodes is assessed by researching for each primary site. As a result, we could consider that stereotactic body radiotherapy could be almost well applied for lymph node oligometastases from the breast, gynecological organs, and prostate. However, doubts remain concerning the usefulness of stereotactic body radiotherapy for cervical node metastases from head and neck cancer or for mediastinal node metastases from lung or esophageal cancer since late toxicities have occurred with a large radiation dose at hypofractionation to major vessels or the central respiratory tract, especially in patients with irradiation histories. In addition, high-dose irradiation is required to control lymph node metastases from colorectal cancer due to its radioresistance, and severe late adverse events would therefore occur in adjacent organs such as the gastrointestinal tract. In cases of lymph node oligometastases with a primary tumor in the stomach or esophagus, stereotactic body radiotherapy should be used limitedly at present because this patient population is not so large and these metastases are often located close to organs at risk. Because of the varied status of recurrence and varied conditions of patients, it is difficult to determine the optimal dose for tumor control. It might be reasonable to determine the treatment dose individually based on dose constraints of adjacent organs. The oligometastatic state is becoming more frequently identified with more sensitive methods of detecting such oligometastases. In addition, there seems to be another type of oligometastases, so-called induced oligometastases, following successful systemic treatment. To determine the optimal indication of stereotactic body radiotherapy for lymph node oligometastases, further investigation about the mechanisms of oligometastases and further clinical studies including a phase III study are needed.

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Multi-institutional Evaluation of Elective Nodal Irradiation and/or Androgen Deprivation Therapy with Postprostatectomy Salvage Radiotherapy for Prostate Cancer

Cited by 29 publications

References 37 publications

Toxicity and Biochemical Outcomes of Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Results of a Randomized Phase III Trial

Toxicity and Biochemical Outcomes of Dose-Intensified Postoperative Radiation Therapy for Prostate Cancer: Results of a Randomized Phase III Trial

Impact of advanced radiotherapy techniques and dose intensification on toxicity of salvage radiotherapy after radical prostatectomy

Stereotactic Radiotherapy for Oligometastases in Lymph Nodes—A Review

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