Prognostic impact of prostate-specific membrane antigen positron emission tomography (PSMA PET) staging for clinically node-positive prostate cancer.

INTRODUCTION: In the current American Joint Committee on Cancer staging system, patients with pelvic nodal metastases are considered stage IV prostate cancer. This study aims to investigate whether men with prostate-specific membrane antigen positron emission tomography (PSMA PET)-detected pelvic node-positive prostate cancer at diagnosis have a better outcome compared to men with node-positive disease identified on conventional imaging. METHODS: This is a retrospective cohort study comparing the outcomes of men with node-positive prostate cancer and disease confined to the pelvis, staged with conventional versus PSMA PET imaging. Men had to be treated definitively with a combination of androgen deprivation therapy and radiation treatment to the prostate and pelvic lymph nodes. Kaplan-Meier and Cox regression analysis was used to compare biochemical failure-free survival (BFFS) and overall survival (OS). RESULTS: Seventy-six men with nodal metastases confined to the pelvis were identified. Fifty-one were detected with PSMA PET while 25 were staged with conventional imaging. PSMA PET staged patients had a lower proportion of Gleason 8-10 disease (78% vs. 96%) as well as a lower median prostate-specific antigen (11 ng/mL vs. 26 ng/mL). BFFS at 4 years was 72% with PSMA PET-detected node-positive disease vs. 38% with conventionally detected node-positive disease. Four-year OS was 93% with PSMA PET staged patients vs. 76% with conventionally staged patients. On multivariate analysis, the PSMA PET staged group was associated with improved BFFS (Adjusted HR = 3.00, 95% CI 1.43, 6.29, P = 0.004) and OS (Adjusted HR = 5.81, 95% CI 1.43, 23.7, P = 0.007). CONCLUSION: Men with PSMA PET-detected node-positive prostate cancer confined to the pelvis have significantly better biochemical control and survival compared to those with node-positive pelvic disease identified through conventional staging.

Decision Regret and Bother With the Addition of Androgen Deprivation Therapy to Definitive Radiation Treatment for Localized Prostate Cancer.

PURPOSE: Androgen deprivation therapy (ADT) combined with radiation treatment (RT) is recommended by the National Comprehensive Cancer Network guidelines for unfavorable intermediate and high-risk localized prostate cancer. Although there is a variable survival benefit conferred by ADT, there are potential side effects to consider for patient decision-making. We aimed to assess the side effects and bother of adding ADT to RT, the degree of regret, and what overall survival (OS) benefit men would want to justify adding or extending the duration of ADT, after their experience with this treatment. METHODS AND MATERIALS: Men receiving ADT with definitive RT completed a questionnaire asking about the side effects and degree of bother from ADT using a 4-point scale. They were also asked about regret, and what survival benefit would warrant ADT. RESULTS: In the study, 846 patients received definitive RT, of whom 356 received ADT and were asked about their experience with ADT. Of these, 234 responded (66%). In 54%, ADT caused some bother, most commonly hot flushes (32%), fatigue (29%), and sexual problems (29%). Five percent regretted receiving ADT "quite a lot" or "very much." Approximately one-third of men deemed a 1% OS benefit from ADT worthwhile, whereas one-third (34%) would want a >10% OS benefit enough to justify choosing ADT again. In addition, 49% of patients who received short-term ADT would accept longer duration ADT for a 6% OS benefit. CONCLUSIONS: Significant regret for ADT was low (5%). There was a clear dichotomy between those who deemed any OS benefit from ADT worthwhile versus those who needed a significant survival benefit to justify the side effects. Given that some men may change their opinion on the relative value of ADT after experiencing its effects, this study emphasizes the importance of revisiting patients after 6 months to given patients an opportunity to renegotiate their treatment.

Radiotherapy for node-positive prostate cancer: 2019 Recommendations of the Australian and New Zealand Radiation Oncology Genito-Urinary group.

The management of node-positive prostate cancer is highly variable, with both locoregional and systemic treatment options available. With the increasing use of novel imaging techniques such as PSMA-PET and MRI, combined with the increasing use of surgery for high-risk prostate cancer, clinical and pathological regional nodal disease is being detected at a higher rate and at an earlier stage than previously. This creates a window for a potentially curative management approach. The role of radiotherapy including optimal radiation target volumes and dose, as well as the timing and duration of accompanying systemic therapy remains uncertain. At a workshop in 2017, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified variations in the management of node-positive prostate cancer identified on primary staging or on histopathology at radical prostatectomy. FROGG reviewed the literature and developed a set of evidence-based recommendations on the appropriate investigation and management of clinically and pathologically node-positive prostate cancer. These recommendations encompass imaging techniques, radiation treatment target volumes and doses, as well as the use of androgen deprivation therapy.

Radiotherapy for recurrent prostate cancer: 2018 Recommendations of the Australian and New Zealand Radiation Oncology Genito-Urinary group.

The management of patients with biochemical, local, nodal, or oligometastatic relapsed prostate cancer has become more challenging and controversial. Novel imaging modalities designed to detect recurrence are increasingly used, particularly PSMA-PET scans in Australia, New Zealand and some European countries. Imaging techniques such as MRI and PET scans using other prostate cancer-specific tracers are also being utilised across the world. The optimal timing for commencing salvage treatment, and the role of local and/or systemic therapies remains controversial. Through surveys of the membership, the Australian and New Zealand Faculty of Radiation Oncology Genito-Urinary Group (FROGG) identified wide variation in the management of recurrent prostate cancer. Following a workshop conducted in April 2017, the FROGG management committee reviewed the literature and developed a set of recommendations based on available evidence and expert opinion, for the appropriate investigation and management of recurrent prostate cancer. These recommendations cover the role and timing of post-prostatectomy radiotherapy, the management of regional nodal metastases and oligometastases, as well as the management of local prostate recurrence after definitive radiotherapy.

Recommendations for followup of stage I and II seminoma: The Princess Margaret Cancer Centre approach.

Testicular seminoma most commonly affects young men and is associated with favourable prognosis. Various followup schedules and imaging protocols for testicular seminoma have been described without overall consensus. We reviewed the literature together with our experience at the Princess Margaret Cancer Centre and present an evidence-based followup approach for patients with stage I and II seminoma.

Testicular seminoma: Scattered radiation dose to the contralateral testis in the modern era.

PURPOSE: Limited data exist on testicular dose measurements using modern radiation treatment techniques and volumes for testicular seminoma. The aim of this study was to report the testicular dose using in vivo measurements in men with testicular seminoma receiving abdominopelvic radiation therapy (APRT) and a modified dog-leg field with and without gonadal shielding. METHODS AND MATERIALS: Men with histologically confirmed testicular seminoma, either newly diagnosed stage II disease or isolated retroperitoneal relapse on surveillance for stage I disease, treated with APRT had testicular dose measurements recorded using MOSFET dosimeters. Those patients wishing to preserve fertility underwent radiation treatment with daily gonadal shielding. Factors that may influence testicular dose including field size, distance of the remaining testis from the radiation field, and patient separation, were also measured. RESULTS: Measurements were performed for 16 men; 10 with gonadal shielding and 6 without. The mean measured dose to the testis in the patients with gonadal shielding was 2.6 cGy (standard error, 0.75; range, 0-13) compared with 28.6 cGy (standard error, 12.6; range, 0-86) in the unshielded group for a 20-fraction treatment. CONCLUSIONS: The use of gonadal shielding during APRT with a modified dog-leg technique results in a low testicular dose that is below the likely threshold for impaired spermatogenesis. In those men wishing to preserve fertility, we recommend the use of gonadal shielding, even with the use of modern radiation therapy techniques.

Long-term outcomes of a phase II trial of moderate hypofractionated image-guided intensity modulated radiotherapy (IG-IMRT) for localized prostate cancer.

PURPOSE: To evaluate long-term radiation toxicity and biochemical control of two moderately hypofractionated radiotherapy regimens for prostate cancer. MATERIAL AND METHODS: Eligible men with localized prostate cancer received image-guided intensity modulated radiotherapy (IG-IMRT) to a dose of 60 or 66Gy in 3Gy fractions in a phase II trial. Endpoints included late gastrointestinal (GI) and genitourinary (GU) toxicity and biochemical failure (FFBF). RESULTS: Ninety-six men received 60Gy and 27 received 66Gy. Accrual to the 66Gy cohort terminated early due to excessive Grade 3-4 late toxicity. Median follow-up was 128months (60Gy) and 108months (66Gy). In the 60Gy cohort, cumulative late Grade ⩾2 GI and GU toxicity at 8years was 4% and 12% respectively. In the 66Gy cohort, late Grade ⩾2 GI and GU toxicity was 21% and 4% respectively at 8years. The 5- and 8-year FFBF for 60Gy was 81% and 66%, and for 66Gy was 88% and 80%. CONCLUSIONS: Moderate hypofractionation with IG-IMRT to 60Gy was associated with favorable late toxicity although late urinary toxicity and biochemical failures were observed beyond 5years. Dose escalation to 66Gy was associated with significantly worse late toxicity.

Important prognostic significance of lymph node density in patients with node positive oral tongue cancer.

BACKGROUND: Lymph node density (LND) has been described as a prognostic factor for survival in patients with head and neck squamous cell carcinoma, particularly of the oral cavity. The aim of this study was to determine the prognostic significance of LND in patients with node positive oral tongue squamous cell carcinoma (OTSCC). METHODS: Patients with pathological node positive OTSCC were identified in a retrospective review of prospectively collected data. The optimal cut-point for LND was determined using the minimum P-value method and the log-rank test. The impact of this LND cut-point on time to disease progression and overall survival was determined. RESULTS: In 72 patients with OTSCC, an LND of 14.3% was found to have the greatest separation using the log-rank test (P < 0.001). LND ≤14.3% was predicted for longer time to disease progression with a median time of 73 months compared to 9.4 months in patients with an LND >14.3% (hazard ratio: 3.43; 95% confidence interval: 1.76-6.70; P < 0.001). LND was also a significant predictor of overall survival with a median overall survival with LND ≤14.3% of 82.3 months, compared with 14.7 months in patients with an LND >14.3% (hazard ratio: 3.28; 95% confidence interval: 1.61-6.68; P = 0.001). Patients with an LND >14.3% experienced a higher rate of regional recurrence. CONCLUSION: Our findings confirm the prognostic significance of LND in patients with node positive OTSCC, with a similar LND cut-point value to other published series. Improving regional control in these high-risk patients may improve outcome.