DOI: https://doi.org/https://doi.org/10.57187/smw.2023.40108
Prostate cancer remains the most common cancer diagnosed in men and a major cause of cancer deaths in Switzerland, with around 6,500 men newly diagnosed and 1,400 men dying from prostate cancer every year (www.krebs.bfs.admin.ch). In recent years, several new diagnostic options and treatment strategies have emerged (figure 1). These are broadly summarized in various international guidelines, but there is much room for interpretation, and several important questions remain debated. To enhance patient management and outcomes, a Swiss consensus meeting was held to promote the coordinated use of innovative diagnostic and therapeutic approaches on a national scale. The consensus discussion focused on the current most important areas of uncertainty, including the staging and treatment of high-risk localized disease, treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and use of new options to treat metastatic castration-resistant prostate cancer (mCRPC).
Figure 1The therapy landscape for prostate cancer, 2023. ADT, androgen deprivation (with LHRH agonist or antagonist or bilateral orchiectomy); ARPI, androgen receptor pathway inhibitor (i.e. abiraterone, apalutamide, enzalutamide); PLND, pelvic lymph node dissection; M0, no evidence of distant metastases; M1 evidence of distant metastases; MDT, metastasis directed therapy. Please refer to https://www.swissmedicinfo.ch for approved indications.
The meeting took place in Bern on November 24, 2022. Most questions were selected from the 2022 international Advanced Prostate Cancer Consensus Conference (APCCC) [1], but some questions were reformulated to facilitate discussion, and some new questions were formulated by the corresponding authors. All questions were circulated to all experts before the meeting to allow participants to prepare. All questions were discussed and subsequently voted on. All votes were submitted electronically and anonymously. Consensus was defined as at least 80% of votes favouring a specific answer. This article summarizes the discussion and voting results and is intended to serve as guidance for the formulation of recommendations by institutional multidisciplinary tumour boards and as a basis for discussion with individual patients. However, these recommendations are not compulsory regulations and cannot replace careful and interdisciplinary shared decision making with patients while considering important individual-specific factors (figure 2).
Figure 2Considerations for individual decisions regarding the treatment of metastatic hormone-sensitive prostate cancer.
The Swiss Group for Clinical Cancer Research (SAKK) invited a total of 22 Swiss prostate cancer experts from different specialties, including urology, radiation oncology, nuclear medicine, pathology and medical oncology, to join the panel. Experts were identified using the network of the SAKK project group for urogenital tumours. Fifteen experts were able to participate in person at the meeting. Participants were permitted to vote on all questions presented, regardless of possible conflicts of interest (e.g., authorship of scientific work discussed).
The co-authors Irene A. Burger, Daniel Eberli, Stefanie Fischer, Silke Gillessen, Guillaume Nicolas, Stephanie Kroeze, Niklaus Schaefer, Thomas Zilli, and Daniel Zwahlen could not attend the consensus meeting in person.
In the first part of the consensus meeting, questions involving modern imaging (i.e., PSMA [prostate-specific membrane antigen] PET/CT and whole-body MRI) as staging modalities in localized prostate cancer were addressed. The possibility of staging at diagnosis using PSMA PET/CT was the centre of the discussion. There was consensus (86%) that staging with PSMA PET/CT is indicated in cases of very high-risk or high-risk localized disease, according to NCCN (National Comprehensive Cancer Network) definitions (table 1), and one-third of panellists also recommended this method of staging in cases of unfavourable intermediate risk.
Table 1 Risk stratification according to the National Comprehensive Cancer Network (NCCN).
| Risk group | Clinical/pathological features | |||
| Very low | Has all of the following: | cT1c | ||
| Gleason 6 (ISUP Grade Group 1) | ||||
| PSA <10 ng/ml | ||||
| <3 prostate biopsy fragments/cores positive, ≤50% cancer in each fragment/core | ||||
| PSA density <0.15 ng/ml/g | ||||
| Low | Has all of the following but does not qualify for very low risk: | cT1–cT2a | ||
| Gleason 6 (ISUP Grade Group 1) | ||||
| PSA <10 ng/ml | ||||
| Intermediate | Has all of the following: | No high-risk group features | ||
| No very high-risk group features | ||||
| Has one or more intermediate risk factors: | cT2b–cT2c | |||
| Gleason 7 (7a = 3 + 4 or 7b = 4 + 3) (ISUP Grade Group 2 or 3) | ||||
| PSA 10–20 ng/ml | ||||
| Favourable intermediate | Has all of the following: | 1 intermediate-risk feature | ||
| Gleason 6 or 7a (ISUP Grade Group 1 or 2) | ||||
| <50% biopsy cores positive (e.g., <6 of 12 cores) | ||||
| Unfavourable intermediate | Has one or more of the following: | 2 or 3 intermediate-risk features | ||
| Gleason 7b (ISUP Grade Group 3) | ||||
| ≥50% biopsy cores positive (e.g., ≥6 of 12 cores) | ||||
| High | Has no very high-risk features and has exactly one high-risk feature: | cT3a OR | ||
| Gleason 8–10 (ISUP Grade Group 4 or 5) OR | ||||
| PSA >20 ng/ml | ||||
| Very high | Has at least one of the following: | cT3b–cT4 | ||
| Primary Gleason pattern 5 | ||||
| 2 or 3 high-risk features | ||||
| >4 cores with Gleason 8–10 (ISUP Grade Group 4 or 5) | ||||
The discussion highlighted that the problem of balancing false positive or ambiguous findings on one hand and sensitivity for locoregional lymph node metastasis (cN1) and/or distant metastases (cM1) on the other hand is difficult given that these findings prompt the determination of a curative versus palliative treatment strategy. Based on the available literature, the sensitivity and specificity of 18F-PSMA-1007 PET/CT (the tracer most often used in Swiss institutions) for detection of locoregional lymph node metastases are 54% and 97%, respectively [2]. A comparative study of conventional staging, both whole-body MRI and 18F-PSMA-1007 PET/CT showed a higher sensitivity and better inter-reader agreement for staging prostate cancer, despite the known limitation of unspecific bone uptake (UBU) [3, 4]. There are very limited data on the comparison of 18F-PSMA-1007 and 68Ga-PSMA-11, and both radiotracers are used in routine clinical practice.
The panel discussed how to proceed in patients with high-risk prostate cancer for whom radical local treatment (radical prostatectomy or radiotherapy) of the primary tumour is planned and who have up to three lesions in the bone with low uptake (as defined by the institution) evident on an upfront 18F-PSMA PET/CT without a correlate on the CT component. The majority of experts (71%) felt that, in general, no further investigations are needed in this case. The rationale is to avoid undertreatment in the case of false positive findings (i.e., inadequate local treatment in the case of wrongly assuming distant metastatic disease). In fact, a recent PSMA PET/CT–guided biopsy study confirmed that the majority of such lesions are caused by false positive uptake [5]. In contrast, in the case of intense uptake (as defined by the institution), only 13% of experts considered this approach appropriate, whereas two-thirds recommended correlative imaging (usually targeted MRI), and 20% recommended a biopsy. There was consensus (93%) not to use whole-body MRI instead of PSMA PET/CT for initial staging.
Active treatment with curative intent encompasses radical prostatectomy or external beam radiation in combination with androgen deprivation therapy. A recent report from the STAMPEDE platform protocol [6] found that the addition of abiraterone/prednisone (for 2 years) and androgen deprivation therapy (for 3 years) to local radiotherapy led to a 9% increase in the 6-year absolute survival rate in men with locally advanced disease (definition according to STAMPEDE protocol: cN1 cM0 disease; or cN0 cM0 disease with at least two of the following: clinical stage T3 or T4, Gleason score 8–10 and prostate-specific antigen [PSA] concentration ≥40 ng/ml). When asked about the relative preference of surgery versus radiotherapy plus androgen deprivation therapy and abiraterone in men with cN0 disease with at least two high-risk criteria, experts showed no preference (40% for both options). If these patients are treated surgically, experts recommended that this be considered a first step of a multimodal approach with a high likelihood that postoperative radiation therapy will be required. In the case of radiotherapy, there was consensus (87%) to include pelvic lymph nodes in the radiation volume. For men with cN1 cM0 disease detectable by modern imaging, a majority of experts (60%) favoured radiotherapy with androgen deprivation therapy and abiraterone, whereas 40% opted for surgery with or without radiotherapy. Notably, three out of four urologists present preferred the combination of radiotherapy, androgen deprivation therapy and abiraterone in this situation, possibly reflecting the perceptions that this treatment is best supported by data and that cN1 likely reflects systemic disease that requires both local and systemic treatment.
In the prostate cancer community, there is some controversy regarding further management in the case of proven lymph node involvement (pN1) following radical prostatectomy and undetectable PSA. In the absence of high-risk features (i.e., Gleason 8–10, positive margins [R1] or pT3), there was consensus (92%) to monitor PSA and only initiate salvage radiotherapy to the prostate bed and pelvic lymph node drainage area in cases of PSA increase. In the case of the presence of two or three of these high-risk features, however, only 43% of experts opted for monitoring and salvage radiotherapy in cases of PSA increase, whereas 57% were in favour of adjuvant radiotherapy, and a minority (21%) of those experts suggested radiotherapy in combination with androgen deprivation therapy. In the case of three or more positive lymph nodes, the latter approach was favoured by 50% of experts in the absence and 67% in the presence of high-risk features. When asked specifically about management of patients following radical prostatectomy (R0) and extended pelvic lymph node dissection without lymph node involvement (pN0) and an undetectable postoperative PSA with a high risk of relapse (i.e., both Gleason 8–10 and pT3b/4 but negative margins [R0]), the majority of experts (72%) opted for monitoring and early salvage radiotherapy with or without androgen deprivation therapy in cases of rising PSA. In a similar scenario but with R1, 53% of the participants opted for adjuvant radiotherapy with or without androgen deprivation therapy as soon as the patient has regained continence after surgery. Generally, in cases of monitoring, restaging should be performed with PSMA PET/CT early, i.e., before PSA rises >0.5ng/ml. For patients treated with radiotherapy after surgery (adjuvant/additive or salvage), 47% of experts advocated the use of androgen deprivation therapy for 6 months, 33% for 12–24 months and 20% not at all. This result reflects a pragmatic interpretation of somewhat conflicting results from the RADICALS-HD trial, which found that, in men receiving postoperative radiotherapy after radical prostatectomy, 24 months of androgen deprivation therapy improved metastasis-free survival (MFS) compared to 6 months of androgen deprivation therapy, while 6 months of androgen deprivation therapy did not improve MFS compared to no androgen deprivation therapy [7]. Treatment recommendations should therefore be individualized based on patient-specific risk factors. The results of the clinically most relevant votes are summarized in figure 3.
Figure 3Staging and treatment of (very) high-risk localized and locally advanced disease (no distant metastasis), with percentages indicating the voting results. ADT, androgen deprivation therapy; cM0, no distant metastases; cN0, no locoregional lymph node metastases; CT, computed tomography; PSA, prostate-specific antigen; PET, positron emission tomography; PSMA, prostate-specific membrane antigen; RT, radiotherapy. Please refer to https://www.swissmedicinfo.ch for approved indications.
Around 5–10% of men with prostate cancer are found to have metastatic disease at first presentation, i.e., have synchronous or de novo metastatic (M1) disease [8]. This initial presentation with M1 disease contrasts with metastatic disease recurring after prior local therapy of the prostate, i.e., metachronous metastatic disease. The latter presents a more favourable prognosis than synchronous metastatic disease [9]. Furthermore, the extent of metastatic disease, namely the presence of visceral disease (e.g., metastases in the liver), and the number and localization of bone metastases are prognostic factors [10]. As a result, in 2015 high volume disease was defined as the presence of visceral metastatic disease and/or the presence of at least four bone metastases, of which at least one was not in the spine or pelvis (with low volume disease representing all situations in which this high volume definition is not met) [10]. However, it should be noted that volume definitions are based on conventional imaging and may be adjusted in the future with the use of novel imaging (such as PSMA-PET or whole-body MRI). Median overall survival in cases of synchronous high volume mHSPC is around 3 years, while median overall survival in cases of metachronous low volume disease is around 8 years [9, 11]. In recent years, early treatment intensification, with the addition of any of the novel androgen receptor pathway inhibitors (ARPI: abiraterone, apalutamide or enzalutamide) or of docetaxel to androgen deprivation therapy, has become the standard of care for most men with mHSPC, depending on the timing of diagnosis and extent of disease [12]. In 2022, two randomized phase 3 studies investigated a triple combination of androgen deprivation therapy, docetaxel and an ARPI (abiraterone in the PEACE-1 study [13] and darolutamide in the ARASENS study [14]). Most men in these studies had de novo mHSPC (all in PEACE-1 and 86% in ARASENS). The addition of either abiraterone or darolutamide to androgen deprivation therapy and docetaxel was associated with longer survival; in the PEACE-1 study this result was restricted to men with high volume disease, for whom median overall survival was prolonged by approximately 1.6 years [13]. A post hoc analysis of the ARASENS study also demonstrated an increased benefit for high volume patients [15]. The panel voted on the question of treatment recommendations for men with synchronous high volume mHSPC: 60% were in favour of a triplet therapy, and 33% recommended doublet therapy (i.e., androgen deprivation therapy plus docetaxel or ARPI). In cases of synchronous low volume disease, there was consensus (80%) for the use of androgen deprivation therapy plus ARPI (while 20% of experts recommended androgen deprivation therapy plus docetaxel or ARPI). For men with metachronous high volume mHSPC, 47% of experts recommended triplet therapy, 27% androgen deprivation therapy plus ARPI and 27% androgen deprivation therapy plus docetaxel or ARPI. For men with metachronous low volume mHSPC, experts reached consensus (93%) for the use of androgen deprivation therapy plus ARPI. In the latter situation, 50% were in favour of treatment until progression (as in the pivotal studies), whereas 29% opted for holding both androgen deprivation therapy and ARPI in the case of a favourable response (i.e., PSA <0.2 ng/ml) after 2 years with rechallenge upon progression (21% recommended discontinuing the ARPI only with rechallenge at progression). In the case of triplet therapy, 40% and 20% of experts were in favour of using darolutamide and abiraterone, respectively, while the remaining 40% had no preference.
Low volume mHSPC (defined as up to four bone metastases) has been shown to be predictive of benefits from local radiotherapy of the prostate, with an 8% gain in absolute overall survival after 3 years [16]. However, none of the participants in this trial had received an ARPI, so it remains uncertain whether a combination of both modalities is needed. Of all Swiss panellists, 47% recommended radiation therapy of the primary tumour in addition to ARPI for the majority of patients, while 47% recommended this approach only in select patients (e.g., younger patients), and 7% did not recommend radiation of the prostate in addition to ARPI.
A majority of experts (73%) agreed that treatment recommendations for MDT should not be based on conventional imaging (i.e., CT plus a bone scan) only. In cases of synchronous low volume mHSPC with one to three bone lesions on PSMA PET/CT, 57% of panellists favoured systemic therapy plus local treatment of the primary tumour plus MDT, while 36% voted for systemic therapy plus local treatment of the primary tumour only. In a similar scenario with metachronous disease, 53% of experts recommended systemic therapy plus MDT, while 27% favoured MDT without systemic treatment, and 20% favoured systemic treatment alone. Clear consensus (93%) was reached regarding the type of MDT, namely radiotherapy. For men with synchronous low volume mHSPC and one to three PSMA PET/CT–positive retroperitoneal lymph nodes, there was no preference (47% of the votes each) for systemic therapy plus local treatment of the primary tumour or systemic therapy plus local treatment of the primary tumour plus MDT. The results of relevant votes are summarized in figure 4. Importantly, the evidence for the effectiveness of MDT in these patients is currently based on small phase 2 trials and is not supported by large trials showing improvement of relevant oncological outcomes.
Figure 4Treatment of metastatic hormone-sensitive prostate cancer (mHSPC), with percentages indicating the voting results. High volume: visceral disease and/or at least 4 bone metastasis of which at least one outside the pelvis and vertebral column. Low volume: high volume criteria not met. ADT, androgendeprivation therapy; ARPI, androgen receptor pathway inhibitor (abiraterone, enzalutamide, apalutamide, darolutamide); CT, computed tomography; MTD, metastasis directed therapy; PET, positron emission tomography; PSA, prostate-specific antigen; PSMA, prostate-specific membrane antigen; RT, radiotherapy. Please refer to https://www.swissmedicinfo.ch for approved indications.
There was consensus (87%) that molecular tests (i.e., next-generation sequencing) would not influence the decision of the first-line treatment for mHSPC, even if available without restrictions. Given the lack of high-quality data on follow-up modalities and intervals during the treatment of mHSPC, the following questions were discussed. In the absence of symptoms, 47% of experts recommended regular imaging, e.g., every 6–12 months, regardless of PSA, while 33% recommended imaging after about 6–12 months and then no more imaging until confirmed PSA progression, and 20% recommended imaging prompted only by rising PSA. As for imaging modality, 53% of panellists opted for conventional imaging (CT with or without a bone scan), whereas 27% and 13% favoured PET/CT and whole-body MRI, respectively. Again, there is very limited evidence for how to interpret, e.g., PSMA PET/CT in patients responding to systemic therapy, and, in fact, in Switzerland PSMA PET/CT is not approved or reimbursed in this situation.
In the absence of alterations of DNA damage response and repair (DDR) genes, all experts (100%) recommended an ARPI as a first-line therapy for mCRPC in men who received androgen deprivation therapy as monotherapy for mHSPC. In cases of time to castration resistance of less than 6 months (i.e., progression within 6 months of the start of androgen deprivation therapy), the use of ARPI or chemotherapy was considered adequate (both options were recommended by 47% of experts). For men treated with an ARPI in the case of mHSPC, all panellists (100%) recommend a switch to chemotherapy, irrespective of time to castration resistance.
Most experts (64%) did not recommend a switch to another ARPI therapy in the majority of patients who have received one line of ARPI and then have progressed. By contrast, 29% deemed a switch appropriate in select patients who had a prior response to abiraterone and subsequently progressed. The basis for the latter recommendation is a study showing a PSA response rate of 19% in this situation [17], while, e.g., abiraterone after enzalutamide was associated with a very low PSA response rate of around 1% [18].
In around 10% of mCRPC cases, tumours harbour a pathogenic BRCA1/2 alteration (around half of which is germ line) [19, 20] that is predictive of benefits from PARP inhibition. Recently, studies combining new endocrine therapies (e.g., abiraterone or enzalutamide) with PARP inhibitors (e.g., olaparib, niraparib or talazoparib) have reported longer radiographic progression-free survival with the combination, irrespective of DDR status, at the cost of increased toxicity and no improvement in overall survival for unselected populations [21–23]. In all these studies, in most cases castration resistance had occurred in patients receiving androgen deprivation therapy as monotherapy. There was consensus (93%) not to combine ARPI with a PARP inhibitor as first-line therapy for mCRPC, irrespective of DDR status. However, for men with mCRPC with a pathogenic BRCA1/2 alteration who developed castration resistance during androgen deprivation therapy and an ARPI (with or without docetaxel), 38% of experts recommended a switch to PARP inhibitor monotherapy, whereas others favoured a switch to chemotherapy (31%) or the addition of a PARP inhibitor to continued ARPI (31%). In cases of other (i.e., not BRCA1/2) pathogenic DNA repair gene alterations, there was consensus (86%) to switch to chemotherapy.
The use of 177Lu-PSMA has led to an overall survival benefit in patients with mCRPC and pretreatment with ARPI and docetaxel if PSMA avidity has been demonstrated on a staging PSMA PET/CT [24]. In men with symptomatic mCRPC who met criteria for treatment with both 223Ra and 177Lu-PSMA, there was consensus (80%) in favour of using 177Lu-PSMA, while 13% of experts had no preference. Furthermore, there was consensus (93%) to recommend 177Lu-PSMA after prior treatment with docetaxel and an ARPI.
The majority of the panel (73%) recommended imaging every 3–6 months for men being treated for mCRPC, regardless of PSA and in the absence of new symptoms. In terms of imaging modality, 47% of panellists favoured CT scans (with or without a bone scan), while 29%, 14% and 7% opted for a CT scan plus a bone scan, whole-body MRI and PET/CT, respectively.
The results of relevant votes are summarized in figure 5.
Figure 5Treatment and staging of metastatic castration-resistant prostate cancer (mCRPC), with percentages indicating the voting results. ADT, androgendeprivation therapy; AR, androgen receptor; ARPI, androgen receptor pathway inhibitor; BRCA, breast cancer gene; DDR, DNA Damage Response and Repair; Lu, Lutetium; mHSPC, metastatic hormone sensitive prostate cancer; CT, computed tomography; MRI, magnet resonance imaging; PARP, Poly ADP-Ribose Polymerase; PET, positron emission tomography; PSA, prostate-specific antigen; PSMA, prostate-specific membrane antigen. Please refer to https://www.swissmedicinfo.ch for approved indications.
Concerns about the availability and costs of modern therapies were prevalent among the participants in the consensus meeting. When asked whether financial cost to the health care system should be considered when making treatment decisions or recommendations, 89% of experts responded “yes, absolutely” and 11% “no, not at all”. It remains to be determined how this can be achieved in daily practice while ensuring optimal treatment for all our patients. First steps might be using generic drugs, if available; de-escalation strategies; and strict adherence to the principle that diagnostic procedures must have a therapeutic consequence.
The authors would like to thank Fabienne Trattner from Medtoday Switzerland and Nadja Burri from the Swiss Group of Clinical Cancer Research (SAKK) in Bern for their great administrative support in organizing the meeting.
The consensus meeting was supported financially by Bayer (Gold Sponsor), Astellas, Bristol Meyers Squibb, AstraZeneca, MSD, Janssen (Silver Sponsors) and Advanced Accelerator Applications (Bronze Sponsor). Neither of the companies was involved in defining the question the panel voted on, and had no role in interpreting the results, or writing the manuscript.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Arnoud J. Templeton has received consulting fees Roche (I) and Bayer (I); he has received honoraria from Astellas (P, I), Janssen (P, I), MSD (I), SAKK (P); he has participated in advisory boards from MSD (P, I), Sanofi (I), Roche (I), Janssen (I), Bayer (I), Pfizer (I), Ipsen (I), Sandoz (I), BMS (I); he has received conference/travel support from Roche (P). – Aurelius Omlin has received consulting fees from Astra Zeneca (I), Astellas (I), Bayer (I), Janssen (I), Molecular Partners (I), MSD (I), Myriad (I), Pfizer (I), Roche (I), Sanofi Aventis (I) and from Novartis (P), Janssen (P), Bayer (P), MSD (P), AstraZeneca (P), Merck (P), Astellas (P); honorary for Speakers Bureau from Astellas (I), Bayer (I), Janssen (I); payment for expert testimony from Astellas (I), Novartis (I), MSD/AstraZeneca (I); travel support from Astellas, Bayer, Janssen, Sanofi Aventis. – Dominik Berthold has received consulting fees from Bayer (I), MSD (I) and BMS (I) and honorary from Astellas (I), Janssen (I) and Astra-Zeneca (I); travel support from Janssen (I), Ipsen (I). – Jörg Beyer has received honorary from Astellas, Bayer, Ispen, Janssen, Merck, Pfizer, Roche. – Irene A. Burger has no conflicts of interest to declare. – Daniel Eberli has received grants from Novartis-Foundation, Astellas, Sutter Söttner Foundation, Angela Reiffer Foundation, Hitz Sprenger Foundation, Julias Müller Foundation, Niermaier Foundation, Meddiscovery, SNF. He has received honoraria from FomF, Taiwan Urological Association, Janssen Cilag, Intuitive Surgical, Debiopharm. Travel support from Bayer. He has participated in advisory boards from Myriad, Bayer, Janssen Cilag, Astellas, Intuitive Surgical. He reports stocks from Muvon therapeutics and OnTrack Diagnostics. – Daniel Engeler has received financial support from Bayer, Astellas, Bristol Meyers Squibb, AstraZeneca, MSD, Janssen and Advanced Accelerator Applications for support of Expert Meeting; Honorary from Janssen, travel support from Debiopharm, and has participated in advisory boards from MSD, Ipsen and Janssen. – Christian Fankhauser has no conflicts of interest to declare. – Stefanie Fischer has received honorary for Speakers bureau from Janssen (I) and har participated in an advisory board for Ipsen (I). – Silke Gillessen has received consulting fees from Tolremo (I); honorary as speaker from Silvio Grasso Consulting(I), WebMD-Medscape (I), ESMO (P, I), Orikata (P), SAKK (P,I), Beijing United Family Hospital and Clinics(P), DESO (P), SAMO (P), Cold Spring Harbour Laboratory NY (I), ASCO GU (I); Travel support from Proteomedix (P), AstraZeneca (P); Patent: WO2009138392; Advisory boards from Janssen (I), MSD (I, P), Bayer (I), Roche (I), Astellas (I), Pfizer (I), Telixpharma (I), Britol-Myers Squibb (I), AAA International (I), Orion (I), Novartis (I), Modra Pharmaceuticals (I), AstraZeneca (I), Myriad genetic (I), Amgen (P, I); she has a leadeship role in the scientific committee Pfizer Forschungspreis (I). – Guillaume Nicolas has received honorary from Janssen-Cilag. – Stephanie Kroeze has received support for attending meetings from EAU 2023, ESTRO 2023, ESTRO/ACROP and participates in the followin scientific committees unpaid: European Multidisciplinary Congress on urological cancers 2021-2023, Scientific Association of Swiss Radiation Oncology, 2023, and Swiss Society of Radiation Oncology Weiterbildungkommission. – Anja Lorch has received consulting fees from Astellas, Astra Zeneca, Bayer, BMS, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer and Roche and has participated in advisory boards from Astellas, Astra Zeneca, Bayer, BMS, Ipsen, Janssen, Merck, MSD, Novartis, Pfizer and Roche; she received travel support from Ipsen. She is a member of following committees: SAKK, EAU, DGHO, ESMO and DKG. – Michael Müntener has received honorary from Janssen (P). – Alexandros Papachristofilou has received an honorary from Debiopharm, Janssen, Merck and Sanofi and travel support from Bayer, Astellas and AstraZeneca. He is a member of "Rising Tide Foundation for Clinical Cancer Research" and" Swiss Group for Clinical Cancer research". – Niklaus Schaefer has no conflicts of interest to declare. – Daniel Seiler has no conflicts of interest to declare. – Frank Stenner has received consulting fees from Roche, MSD, BMS, Astellas and Takeda, an honorary from Takeda, and travel support from Roche, BMS and Gilead. – Petros Tsantoulis has received consulting fees from Novartis (I) and Janssen (I), honorary from SAKK (I) and MSD (I), payment for expert testimony from Pfizer (I) and Novartis (I), travel support from Sanofi (I), Lilly (I), Janssen, and has participated in an advisory board from Roche (I), Sanofi (I), Astellas (I), MSD (I), Bayer (I), BMS (I), Pfizer (I), Janssen (I), Ipsen (I), Novartis (I). – Tatjana Vlajnic has received honorary from Janssen. – Thomas Zilli has received a grant or contract of entity from Varian/Debiopharm (I), an honorary from Janssen, Telix and Astellas and a travel grant from Debiopharm. – Daniel Zwahlen has no conflicts of interest to declare. – Richard Cathomas has received consulting fees from Astellas (I), Janssen (P), Bayer (I), Sanofi (I)MSD (I), BMS (I), Roche (I), Pfizer (I), Astra Zeneca (I), Merck (P), Ipsen (I) and an honorary from Astellas (I), Janssen (P), Merck (P), Sandoz (I), Ipsen(I). He has received travel support from Ipsen (I) and is a member of the SAKK board (I).
P, personal compensation; I, compensation to institution
1. Gillessen S, Bossi A, Davis ID, de Bono J, Fizazi K, James ND, et al. Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022. Eur Urol. 2022.
2. Ingvar J, Hvittfeldt E, Trägårdh E, Simoulis A, Bjartell A. Assessing the accuracy of [18F]PSMA-1007 PET/CT for primary staging of lymph node metastases in intermediate- and high-risk prostate cancer patients. EJNMMI Res. 2022 Aug;12(1):48. 10.1186/s13550-022-00918-7
3. Anttinen M, Ettala O, Malaspina S, Jambor I, Sandell M, Kajander S, et al. A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE). Eur Urol Oncol. 2021 Aug;4(4):635–44. 10.1016/j.euo.2020.06.012
4. Grünig H, Maurer A, Thali Y, Kovacs Z, Strobel K, Burger IA, et al. Focal unspecific bone uptake on [18F]-PSMA-1007 PET: a multicenter retrospective evaluation of the distribution, frequency, and quantitative parameters of a potential pitfall in prostate cancer imaging. Eur J Nucl Med Mol Imaging. 2021 Dec;48(13):4483–94. 10.1007/s00259-021-05424-x
5. Vollnberg B, Alberts I, Genitsch V, Rominger A, Afshar-Oromieh A. Assessment of malignancy and PSMA expression of uncertain bone foci in [18F]PSMA-1007 PET/CT for prostate cancer-a single-centre experience of PET-guided biopsies. Eur J Nucl Med Mol Imaging. 2022 Sep;49(11):3910–6. 10.1007/s00259-022-05745-5
6. Attard G, Murphy L, Clarke NW, Cross W, Jones RJ, Parker CC, et al.; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022 Jan;399(10323):447–60. 10.1016/S0140-6736(21)02437-5
7. Parker CC, Clarke N, Cook A, Catton C, Cross WR, Kynaston H, et al. Duration of androgen deprivation therapy (ADT) with post-operative radiotherapy (RT) for prostate cancer: First results of the RADICALS-HD trial (ISRCTN40814031). Annals of Oncology 2022;33 (suppl_7):S808-S69. (LBA 9).
8. Rebello RJ, Oing C, Knudsen KE, Loeb S, Johnson DC, Reiter RE, et al. Prostate cancer. Nat Rev Dis Primers. 2021 Feb;7(1):9. 10.1038/s41572-020-00243-0
9. Francini E, Gray KP, Xie W, Shaw GK, Valença L, Bernard B, et al. Time of metastatic disease presentation and volume of disease are prognostic for metastatic hormone sensitive prostate cancer (mHSPC). Prostate. 2018 Sep;78(12):889–95. 10.1002/pros.23645
10. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015 Aug;373(8):737–46. 10.1056/NEJMoa1503747
11. Gravis G, Boher JM, Chen YH, Liu G, Fizazi K, Carducci MA, et al. Burden of Metastatic Castrate Naive Prostate Cancer Patients, to Identify Men More Likely to Benefit from Early Docetaxel: Further Analyses of CHAARTED and GETUG-AFU15 Studies. Eur Urol. 2018 Jun;73(6):847–55. 10.1016/j.eururo.2018.02.001
12. Cornford P, van den Bergh RC, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II-2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. Eur Urol. 2021 Feb;79(2):263–82. 10.1016/j.eururo.2020.09.046
13. Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Fléchon A, et al.; PEACE-1 investigators. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2×2 factorial design. Lancet. 2022 Apr;399(10336):1695–707. 10.1016/S0140-6736(22)00367-1
14. Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, et al.; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar;386(12):1132–42. 10.1056/NEJMoa2119115
15. Hussain M, Tombal B, Saad F, Fizazi K, Sternberg CN, Crawford ED, et al. Darolutamide Plus Androgen-Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer by Disease Volume and Risk Subgroups in the Phase III ARASENS Trial. J Clin Oncol. 2023 Jul;41(20):3595–607. 10.1200/JCO.23.00041
16. Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al.; Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018 Dec;392(10162):2353–66. 10.1016/S0140-6736(18)32486-3
17. de Bono JS, Chowdhury S, Feyerabend S, Elliott T, Grande E, Melhem-Bertrandt A, et al. Antitumour Activity and Safety of Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Abiraterone Acetate Plus Prednisone for ≥24 weeks in Europe. Eur Urol. 2018 Jul;74(1):37–45. 10.1016/j.eururo.2017.07.035
18. Attard G, Borre M, Gurney H, Loriot Y, Andresen-Daniil C, Kalleda R, et al.; PLATO collaborators. Abiraterone Alone or in Combination With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer With Rising Prostate-Specific Antigen During Enzalutamide Treatment. J Clin Oncol. 2018 Sep;36(25):2639–46. 10.1200/JCO.2018.77.9827
19. Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015 May;161(5):1215–28. 10.1016/j.cell.2015.05.001
20. de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May;382(22):2091–102. 10.1056/NEJMoa1911440
21. Clarke NW, Armstrong AJ, Thiery-Vuillemin A, Oya M, Shore N, Loredo E, et al. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evid. 2022;2022(9):1. 10.1056/EVIDoa2200043
22. Chi KN, Rathkopf DE, Smith MR, Efstathiou E, Attard G, Olmos D, et al. Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. Journal/ASCO GU abstract #12 2022;
23. Pfizer. Pfizer Announces Positive Topline Results from Phase 3 TALAPRO-2 Trial 2022 (Press release on Oct 4);
24. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, et al.; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep;385(12):1091–103. 10.1056/NEJMoa2107322