Pre-treatment nomogram for biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for clinically localised prostate cancer

Parker, Christopher; Norman, A.; Huddart, Robert; Horwich, A.; Dearnaley, David P.

doi:10.1038/sj.bjc.6600160

Cited by 14 publications

(4 citation statements)

References 34 publications

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“…The 5-year PSA control rates were 69 and 79%, respectively (P ¼ 0.06). This trial included patients with better prognostic features (for example, median PSA 8 ng ml À1 compared to 14 ng ml À1 in our current study) (Shipley et al, 1999;Parker et al, 2002). Subgroup analysis of the 106 men with presenting PSA levels greater than 10 ng ml À1 showed biochemical control rates of 48 and 75% (P ¼ 0.01) for the 70 and 78 Gy groups, respectively.…”

Section: Discussionmentioning

confidence: 99%

Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects

et al. 2005

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Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3 -6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58 -81%) in the 74 Gy group vs 59% (95% CI 45 -70%) in the 64 Gy group. There were 23 failures in the 74Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38 -1.10, P ¼ 0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53 -77% vs 63%, 95% CI 50 -74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50 -1.86, P ¼ 0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men had persistent XGrade 1 bowel or bladder side effects, respectively. Statistically significant increases in acute bladder side effects were seen after treatment in the men receiving 74 Gy (P ¼ 0.006), and increases in both acute bowel side effects during treatment (P ¼ 0.05) and acute bladder sequelae (P ¼ 0.002) were recorded for men in the 1.5 cm margin group. While statistically significant, these differences were of short duration and of doubtful clinical importance. Late bowel side effects (RTOGX2) were seen more commonly in the 74 Gy and 1.5 cm margin groups (P ¼ 0.02 and P ¼ 0.05, respectively) in the first 2 years after randomisation. Similar results were found using the LENT SOM assessments. No significant differences in late bladder side effects were seen between the randomised groups using the RTOG scoring system. Using the LENT SOM instrument, a higher proportion of men treated in the 74 Gy group had Grade X3 urinary frequency at 6 and 12 months. Compared to baseline scores, bladder symptoms improved after 6 months or more follow-up in all groups. Sexual function d...

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Section: Discussionmentioning

confidence: 99%

Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects

et al. 2005

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“…In the UK, contemporary surgical series from tertiary centres have identified that up to 13% of men will have high‐grade disease [2]. In published UK and USA EBRT series, high‐risk disease has been reported in 17–19% of men [3,4]. In our own institution a recent review identified 10% of men treated by RP and 16% of men treated by EBRT have high‐risk disease ([5] and unpublished data).…”

Section: Introductionmentioning

confidence: 97%

The role of surgery in high‐risk localised prostate cancer

et al. 2011

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The optimal management of high‐risk localised prostate cancer is a major challenge for urologists and oncologists. It is clear that multimodal therapy including radical local treatment is needed in these men to achieve the best outcomes. External beam radiotherapy (EBRT) is an essential component of therapy either as a primary or adjuvant treatment. However, the role of radical prostatectomy (RP) is more controversial. Both methods are currently valid therapy options. There have been many individual studies of EBRT and RP in high‐risk disease, but no good quality large prospective randomized trials. In EBRT, combination with neoadjuvant plus long‐term adjuvant androgen‐deprivation therapy (ADT) has been conclusively shown to improve outcomes and is widely considered the standard of care. However, the role of RP has achieved recent prominence with several important studies. Published data from prospective randomized trials in patients after RP have shown that in men with adverse pathological features at surgery, the addition of adjuvant RT improves biochemical‐free and progression‐free survival. More recently, studies from large‐volume centres comparing EBRT and RP have provided intriguing suggestions of better outcomes with RP as the primary treatment. An important question therefore, is which of the two methods provides the best outcome in men with localised high‐risk disease. Crucially, does the combination of RP and selective adjuvant EBRT provide clinically significant better outcomes compared with EBRT alone? In this review we discuss the current evidence for the role of RP for high‐risk localised prostate cancer and define the parameters and urgent need for a prospective trial to test the role of surgery for this group of patients.

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“…Nomograms addressing biochemical and/or survival outcomes in prostate cancer have been published for patients receiving EBRT alone [ 4 - 5 , 7 , 10 - 17 ], one of RP or EBRT [ 18 - 20 ], RP or RP followed by salvage EBRT [ 21 - 28 ], and for LDR brachytherapy or LDR brachytherapy followed by EBRT [ 29 - 31 ], each reporting variable rates of ADT utilization. Similarly, the majority of published nomograms incorporate the same set of three key prognostic factors as reported in risk stratification systems (pre-treatment PSA, T stage and Gleason score), with some exceptions in studies reporting on RP or EBRT alone [ 10 , 18 ] or RP with EBRT salvage [ 21 , 23 - 28 ].…”

Section: Introductionmentioning

confidence: 99%

Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer

Warner

Pickles

Crook

et al. 2015

Cureus

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Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II “Phoenix” definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database.Methods and Materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy (n=822). Multivariable Cox regression analysis for BFFS was performed separately for each cohort and used to generate clinical nomograms predictive of 5-year BFFS. Nomograms were validated using calibration plots of nomogram predicted probability versus observed probability via Kaplan-Meier estimates.Results: Patients receiving LDR brachytherapy had a mean age of 64 ± 7 years, a mean baseline PSA of 6.3 ± 3.0 ng/mL, 75% had a Gleason 6, and 15% had a Gleason 7, whereas patients receiving EBRT had a mean age of 70 ± 6 years, a mean baseline PSA of 11.6 ± 10.7 ng/mL, 30% had a Gleason 6, 55% had a Gleason 7, and 14% had a Gleason 8-10. Nomograms for 5-year BFFS included age, use and duration of androgen deprivation therapy (ADT), baseline PSA, T stage, and Gleason score for LDR brachytherapy and an ADT (months), baseline PSA, Gleason score, and biological effective dose (Gy) for EBRT.Conclusions: Clinical nomograms examining 5-year BFFS were developed for patients receiving either LDR brachytherapy or conventionally fractionated EBRT and may assist clinicians in predicting an outcome. Future work should be directed at examining the role of additional prognostic factors, comorbidities, and toxicity in predicting survival outcomes.

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Pre-treatment nomogram for biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for clinically localised prostate cancer

Cited by 14 publications

References 34 publications

Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects

Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects

The role of surgery in high‐risk localised prostate cancer

Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer

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