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Contemporary role of postoperative radiotherapy for prostate cancer.

ABSTRACT: While radical prostatectomy (RP) has provided long-term disease control for the majority of patients with localized prostate cancer (CaP), nearly 30% of all surgical patients have disease progression. For high-risk patients, more than half of men experience disease recurrence within 10 years. Postoperative radiotherapy is the only known potentially curative treatment for a large number of patients following prostatectomy. Lately, there have been several advances with the potential to improve outcomes for patients undergoing postoperative radiotherapy. This article will give an overview of the existing literature and current controversies on: (I) timing of postoperative radiation; (II) use of concomitant androgen deprivation therapy; (III) optimal dose to the prostate bed; (IV) use of hypofractionation; (V) elective treatment of the pelvic lymph nodes; (VI) novel imaging modalities, and (VII) genomic biomarkers.

SUBMITTER: Dal Pra A

PROVIDER: S-EPMC6043752 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Contemporary role of postoperative radiotherapy for prostate cancer.

Dal Pra Alan A Abramowitz Matthew C MC Stoyanova Radka R Pollack Alan A

Translational andrology and urology 20180601 3

While radical prostatectomy (RP) has provided long-term disease control for the majority of patients with localized prostate cancer (CaP), nearly 30% of all surgical patients have disease progression. For high-risk patients, more than half of men experience disease recurrence within 10 years. Postoperative radiotherapy is the only known potentially curative treatment for a large number of patients following prostatectomy. Lately, there have been several advances with the potential to improve out ...[more]

PMID: 30050800

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Project description:ContextAndrogen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk-benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease.ObjectiveReview the published experience with currently available ADT approaches in various contemporary clinical settings of PCa and reported serious treatment-related adverse events. This review addresses the level of evidence associated with the use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this paper discusses evolving approaches targeting androgen receptor signaling pathways and emerging evidence from clinical trials with newer compounds.Evidence acquisitionA comprehensive review of the literature was performed, focusing on data from the last 10 yr (January 2000 to July 2011) and using the terms androgen deprivation, hormone treatment, prostate cancer and adverse effects. Abstracts from trials reported at international conferences held in 2010 and 2011 were also evaluated.Evidence synthesisData from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone-releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality.ConclusionsAlthough ADT is an effective treatment of PCa, consistent long-term benefits in terms of quality and quantity of life are predominantly evident in patients with advanced/metastatic disease or when ADT is used in combination with RT (<72Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk-benefit ratio.

Project description:ContextRadiotherapy (RT) is a valid adjuvant treatment for men with high-risk pathological features after radical prostatectomy and a salvage treatment for biochemical recurrence. A major inconvenience is that RT takes course over 7-8 wk in these settings, which has been shown to limit its use. Retrospective and pilot prospective investigations suggest that hypofractionation may provide noninferior outcomes but report variable results regarding toxicities. Additionally, our evolving understanding of prostate cancer radiobiology suggests that hypofractionated regimens may not increase toxicity.ObjectiveWe examine and review the rationale and clinical evidence of hypofractionated RT in the adjuvant and salvage settings for prostate cancer.Evidence acquisitionWe reviewed relevant literature, with a particular focus on recent studies employing hypofractionated RT.Evidence synthesisHypofractionated RT in the adjuvant or salvage setting is not a standard option for prostate cancer RT outside of an investigational trial. While smaller studies show conflicting data regarding toxicity, initial evidence from larger clinical trials appears to demonstrate that hypofractionated postoperative RT is as effective and safe as conventionally fractionated courses.ConclusionsWith the growing acceptance of hypofractionation across other cancer sites and the rise of extreme hypofractionation for definitive prostate cancer treatment, hypofractionated postoperative therapy for prostate cancer is poised to become an option, as it may reduce the burden on men and treatment centers while maintaining clinical efficacy and safety. Prospective trials are currently ongoing to address efficacy and safety concerns.Patient summaryPostoperative radiotherapy is a potentially curative treatment for patients with high-risk disease or recurrence after surgery. Shortening of the treatment regimen with the availability of modern treatment delivery techniques in conjunction with the integration of molecular imaging information to refine treatment volumes may improve therapeutic benefit without increasing toxicity.

Project description:BACKGROUND:Adjuvant (ART) and salvage radiotherapy (SRT) are two common concepts to enhance biochemical relapse free survival (BCRFS) in patients with prostate cancer (PC). We analyzed differences in outcome between ART and SRT in patients with steep decline of PSA-levels after surgery to compare outcome. METHODS:We evaluated 253 patients treated with postoperative RT with a median age of 66?years (range 42-85?years) treated between 2004 and 2014. Patients with additive radiotherapy due to PSA persistence and patients in the SRT group, who did not achieve a postoperative PSA level?<0.1?ng/mL were excluded. Hence, data of 179 patients was evaluated. We used propensity score matching to build homogenous groups. A Cox regression model was used to determine differences between treatment options. Median follow-up was 32.5?months (range 1.4-128.0?months). RESULTS:Early SRT at PSA levels <0.3?ng/mL was associated with significant longer BCRFS than late SRT (HR: 0.32, 95%-CI: 0.14-0.75, p =?0.009). Multiple Cox regression showed pre-RT PSA level, tumor stage, and Gleason score as predictive factors for biochemical relapse. In the overall group, patients treated with either ART or early SRT showed no significant difference in BCRFS (HR: 0.17, 95%-CI: 0.02-1.44, p =?0.1). In patients with locally advanced PC (pT3/4) BCRFS was similar in both groups as well (HR: 0.21, 95%-CI:0.02-1.79, p =?0.15). CONCLUSION:For patients with PSA-triggered follow-up, close observation is essential and early initiation of local treatment at low PSA levels (<0.3?ng/mL) is beneficial. Our data suggest, that SRT administered at early PSA rise might be equieffective to postoperative ART in patients with locally advanced PC. However, the individual treatment decision must be based on any adverse risk factors and the patients' postoperative clinical condition. STUDY REGISTRATION:The present work is approved by the Ethics Commission of the Technical University of Munich (TUM) and is registered with the project number 320/14.

Project description:BACKGROUND:Despite increasing utilization of proton-beam therapy (PBT) in the postprostatectomy setting, no data exist regarding toxicity outcomes relative to intensity-modulated radiotherapy (IMRT). The authors compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicity outcomes in patients with prostate cancer (PC) who received treatment with postprostatectomy IMRT versus PBT. METHODS:With institutional review board approval, patients with PC who received adjuvant or salvage IMRT or PBT (70.2 gray with an endorectal balloon) after prostatectomy from 2009 through 2017 were reviewed. Factors including combined IMRT and PBT and/or concurrent malignancies prompted exclusion. A case-matched cohort analysis was performed using nearest-neighbor 3-to-1 matching by age and GU/GI disorder history. Logistic and Cox regressions were used to identify univariate and multivariate associations between toxicities and cohort/dosimetric characteristics. Toxicity-free survival (TFS) was assessed using the Kaplan-Meier method. RESULTS:Three hundred seven men (mean ± SD age, 59.7 ± 6.3 years; IMRT, n = 237; PBT, n = 70) were identified, generating 70 matched pairs. The median follow-up was 48.6 and 46.1 months for the IMRT and PBT groups, respectively. Although PBT was superior at reducing low-range (volumes receiving 10% to 40% of the dose, respectively) bladder and rectal doses (all P ? .01), treatment modality was not associated with differences in clinician-reported acute or late GU/GI toxicities (all P ? .05). Five-year grade ?2 GU and grade ?1 GI TFS was 61.1% and 73.7% for IMRT, respectively, and 70.7% and 75.3% for PBT, respectively; and 5-year grade ?3 GU and GI TFS was >95% for both groups (all P ? .05). CONCLUSIONS:Postprostatectomy PBT minimized low-range bladder and rectal doses relative to IMRT; however, treatment modality was not associated with clinician-reported GU/GI toxicities. Future prospective investigation and ongoing follow-up will determine whether dosimetric differences between IMRT and PBT confer clinically meaningful differences in long-term outcomes.

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Contemporary role of postoperative radiotherapy for prostate cancer.

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Contemporary role of postoperative radiotherapy for prostate cancer.

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