Introduction
Prostate cancer is the most common malignancy in men and a leading cause of cancer deaths in Switzerland with around 7800 men newly diagnosed and 1360 dying from prostate cancer every year (1). Ongoing global efforts to improve outcomes for men with prostate cancer lead to an ever-growing body of evidence from clinical trials resulting in an increasing number of diagnostic and therapeutic strategies (Fig. 1). While in many cases treatment decisions may seem quite straight forward to those with a clinical focus on prostate cancer, this may be less so for those more involved in other areas of oncology and medicine. Furthermore, there remain several areas of uncertainty and debatable interpretation of data and their application to individual patients is not necessarily represented in clinical studies. To provide guidance for daily practice, the corresponding authors of this article organized a consensus meeting, which took place on August 15, 2024 in Bern, Switzerland. During this meeting, 63 pre-defined questions were discussed and voted on. The majority of these questions were selected from the international Advanced Prostate Consensus Conference (APCCC) 2024 (2), some were reformulated or adjusted to Swiss conditions to facilitate discussion, and some were newly added by the corresponding authors. All questions were circulated beforehand for preparation to all attending experts. The questions were discussed at the meeting and subsequently voted on. All votes were done electronically and anonymously. Consensus was defined if at least 75 % of all votes favored a specific answer; strong consensus needed an agreement of at least 90 % of votes. In cases of conflicts of interest or when not feeling adequately qualified to answer a question, it was recommended to vote “abstain”. Such votes were excluded for calculation of the percentages for the distribution of other answers. Assumptions applicable to all questions unless stated otherwise and the definitions of terms and treatment options can be found in the Supplementary Appendix online.
The questions were grouped in 5 main categories
1. high-risk localized and locally advanced prostate cancer (Q 1–11)
2. PSA persistence and biochemical recurrence (Q 12–27),
3. metastatic hormone-sensitive prostate cancer (mHSPC) (Q 28–43)
4. metastatic castration-resistant prostate cancer (mCRPC) (Q 44–58)
5. selected miscellaneous topics (Q 59–63).
As in a previous version of this Swiss consensus statement (3), this article summarizes the discussion and voting results and is intended to serve as guidance for formulating recommendations during institutional multidisciplinary tumor boards and as basis for discussion with individual patients. As such, these recommendations are not imperative regulations and cannot replace careful and interdisciplinary shared decision making with patients considering important individual factors. This Swiss consensus is intended to complement the views of the APCCC 2024 views from a local perspective in Switzerland; we strongly encourage to consult the original publication for the complete voting results of the international expert panel (2).
Composition of the panel
In total, 23 Swiss prostate cancer experts from different specialties including medical oncology, radiation oncology, urology, nuclear medicine, and pathology were invited by the corresponding authors. They were identified through the network of the Swiss group for clinical cancer research (SAKK) project group for genitourinary tumors. Three experts were unable to participate in person at the meeting and cast their vote electronically.
High-risk localized and locally advanced prostate cancer
Staging of localized prostate cancer
In localized prostate cancer, the T-stage influences the risk category and thus, in case of radiotherapy, the recommended duration of concurrent androgen deprivation therapy (ADT). Traditionally, staging of the primary tumor is assessed clinically by palpation of the prostate and this approach is reinforced in contemporary guidelines (4). However, with the advent of modern imaging, namely multi parametric MRI and PSMA-PET/CT as staging modalities, discrepancies may occur, e.g. a non-palpable tumor (T1c) may show extracapsular extension (imaging T3a) or seminal vesical infiltration (imaging T3b). Among the panelists, there was consensus (86 %) to treat the primary as T3 in case of clear evidence of T3 disease on MRI and/or PSMA-PET/CT in the majority of men with localized ISUP grade group >2 prostate cancer and clinically T1 or T2 disease, i.e. regardless of stage on digital rectal examination (Fig. 2).
Another challenge with PSMA PET/CT imaging relates to the problem of false positive or ambiguous findings since misclassification of lesions as distant spread (cM1 disease) may trigger palliative treatment decisions rather than a curative approach. The panel emphasized that reports must contain accurate declaration of PSMA ligands used for PET/CT and standardized reporting (PSMA-RADS) and subsequently discussed how to proceed in patients with high-risk localized or locally advanced prostate cancer and one PSMA PET-positive bone lesion without a correlate on the CT component of the PSMA PET/CT. A slight majority of the experts (57 %) recommended no further investigation, i.e. to treat the patient in curative intent (as cM0) while the others (43 %) recommended correlative imaging, e.g. MRI.
Treatment of high-risk localized prostate cancer
Active treatment with curative intention encompasses radical prostatectomy (RP) or external beam radiation therapy (RT) in combination with androgen deprivation therapy (ADT). When proceeding with radical prostatectomy, there are different approaches with regard to lymph node dissection. While it is generally accepted that extended pelvic lymph node dissection (ePLND) improves staging, the oncological benefit of the procedure remains without level 1 evidence. In patients with negative staging PSMA PET (cN0 cM0), that misses up to 60 % lymph nodes that are found to be positive after surgery (5, 6), there was a consensus to recommend ePLND in high-risk disease (100 %), while 50 % also recommend ePLND in intermediate risk disease for patients with a calculated 2012 or 2019 Briganti lymph node involvement (LNI) risk-score of > 5 % or > 7 %, respectively (7). In case of ePLND and pathologically involved pelvic lymph nodes (pN+) in the histological workup, there is consensus (87 %) in case of 1–2 positive nodes to monitor patients with regular PSA testing and to treat with salvage RT (SRT) only if PSA rises. For patients with 3 or more positive pelvic lymph nodes, the panel favored adjuvant radiotherapy (65 %), while a minority considered monitoring and early salvage therapy (35 %). With radiotherapy, 74 % opted for the addition of ADT (for 6 months (40 %) or for 24 months (34 %)). Of note, in the RADICAS-HD study, the addition of ADT for 24 months improved metastasis-free survival (MFS) compared to 6 months of ADT (8) while 6 months of ADT did not improve MFS compared to radiotherapy alone (9).
When radiotherapy to the prostate is chosen, there was a strong consensus (100 %) to use moderate hypofractionation (i.e. 2.5–3.0 Gy per fraction). Regarding the question of the inclusion of the pelvic lymph nodes in the radiation field in patients with high-risk localized/locally advanced disease and negative PSMA PET, which may result in better outcomes (10), 47 % voted in favor of RT to the pelvic lymph nodes, while 42 % only recommended this in selected patients based on risk factors (presence of multiple high-risk criteria), and 11 % did not recommend RT to the pelvic lymph nodes. A large prospective study (STAMPEDE) involving 1974 men with high-risk non-metastatic prostate cancer (defined as cN1 cM0 or cN0 cM0 with at least two of the following: clinical stage T3 or T4, Gleason score 8–10 (ISUP grade 4 or 5), prostate-specific antigen (PSA) concentration ≥ 40 ng/ml) investigated the role of adding two years of abiraterone/prednisone to the treatment with radiotherapy plus 3 years of ADT. A significant 9 % absolute increase in 6-year-survival rate was reported in the meta-analysis of two trials of the STAMPEDE platform protocol (11). Asked about the relative preference of surgery as part of a multimodality approach versus radiotherapy plus long-term ADT versus the latter combined with two years of abiraterone in men with cN0 disease on PSMA PET/CT with 2 or 3 of the 3 risk factors mentioned above, there was a strong consensus (96 %) to treat with radiotherapy plus ADT for three years plus abiraterone/prednisone for 2 years. Of note, in the previous Swiss consensus meeting held in 2022, there was no preference for radiotherapy plus intensified endocrine treatment over surgery (3). The same approach was recommended by most (87 %) for men with cN1 on PSMA PET/CT but no distant lesions (cM0). 81 % of the panelists indicated that it is appropriate to substitute abiraterone by another androgen receptor pathway inhibitor (ARPI), i.e. apalutamide, enzalutamide or darolutamide in men who are not eligible for abiraterone. Likewise, a majority (71 %) voted in favor of discontinuing the ADT together with abiraterone after two years (instead of three years) even in the absence of relevant toxicity, while 24 % only voted in favor of this option in selected patients, e. g. those with a relevant cardiovascular history.
PSA persistence and biochemical recurrence
PSA persistence after radical prostatectomy
The PSA is expected to drop to < 0.1 ng/ml following radical prostatectomy. When this level is not achieved, it is perceived that treatment decisions should be based on the absolute PSA level and on the presence of risk factors (R1, pT3, ISUP grade group 4–5). In a patient after radical prostatectomy and ePLND (pN0) with a negative postoperative PSMA PET and a PSA of around 0.2 ng/ml and no risk factors, the majority (93 %) would continue to monitor PSA. However, in the same patient but with a PSA level of around 0.7 ng/ml two-thirds of panelists would recommend immediate therapy, whereas one-third would monitor first. If a therapy is recommended, there is no consensus whatsoever regarding the extent of the radiotherapy (prostate bed only or including whole pelvis) nor whether to add ADT at all, for short (i.e. 6 months) or for long (i.e. 24 months) term (Fig. 2). In contrast, when two or more of the risk factors (R1, pT3, ISUP grade group 4–5) are present, there is consensus to recommend immediate therapy (83 %), whereas 65 % recommended radiotherapy to the prostate bed and pelvis and 80 % recommended adding short-term ADT for 6 months (Fig. 2).
PSA recurrence after curative local therapy
After radical prostatectomy, the current EAU guidelines on prostate cancer suggest that “wait and see” remains an option in men with “low-risk” biochemical relapse (defined as PSA doubling time (PSA-DT) > 1 year and ISUP grade group <4) following prostatectomy (4). At our meeting, there was a consensus (82 %) in case of “EAU low-risk” PSA recurrence and a negative PSMA-PET, to measure PSA every 6 months and repeat PSMA-PET if PSA-DT shortens to <1 year. In case of relapse with “EAU high-risk” PSA recurrence (i.e. PSA-DT <1 year and/or ISUP 4–5) and negative PSMA PET however, there was a strong consensus (100 %) in favor of salvage radiotherapy (SRT). There was consensus (76 %) that SRT should include the prostate bed only. Together with SRT 36 %, 41 %, and 23 % recommended addition of none, 6, or 24 months of ADT, respectively. There was also a consensus (77 %) not to use molecular classifiers (e.g. Decipher) to inform the timing of adjuvant radiotherapy versus early SRT in the majority of patients – even though some data suggest that this could be an option (12).
After local radiotherapy and systemic therapy (ADT +/– ARPI) PSA recurrence is defined differently. The classical definition of a PSA rise of > 2.0 ng/ml above nadir (< 0.2 ng/ml) has been discussed controversially more recently. The panel was in consensus that PSA needs to rise > 1.0 ng/ml and over 40 % were in favor of a rise > 2.0 ng/ml before recommending modern imaging. In case of confirmed local recurrence within the prostate and no evidence of distant metastases on PSMA PET (time to biochemical recurrence < 18 months, and/or ISUP grade 4–5 and PSA-DT ≤ 9 months), 57 % recommend local therapy (+/– systemic therapy), whereas 30 % recommend systemic treatment alone. If local therapy is applied, 69 % favor re-irradiation, whereas 19 % opted for salvage prostatectomy and 12 % for other local treatments (e.g. HIFU or irreversible electroporation IRE) after multidisciplinary discussion.
For patients with rising PSA after local therapy (RP and SRT, RP alone, EBRT/ADT alone) with PSA-DT ≤ 9 months, a PSA level of ≥ 1 ng/ml (after RP or RP plus SRT) or ≥ 2 ng/ml (after local EBRT) and no detectable metastases on conventional imaging (pelvic lymph nodes up to 20 mm allowed), the recently published trial EMBARK demonstrated that intermittent therapy with ADT and enzalutamide is associated with an 87 % rate of metastases-free survival at 5 years (13). In case of high-risk non-metastatic HSPC (nmHSPC, according to the definition used in EMBARK, i.e. biochemical relapse with a PSA doubling time of < 9 months after local therapies) and a negative PSMA PET, there was consensus (87 %) to recommend systemic therapy, with 73 % opting for intermittent ADT plus enzalutamide, i.e. hold treatment after around 9 months when PSA is < 0.2 ng/ml. In case of PSMA PET avid lymph nodes in the pelvis and/or retroperitoneum (< 10 mm) 26 % would use metastases directed therapy (MDT) in case of ≤ 5 metastases, 22 % would use systemic therapy alone, and 52 % the combination of systemic therapy and MDT. In case of systemic therapy there was consensus to use intermittent ADT plus enzalutamide (80 %). The flow diagram for localized disease is shown in (Fig. 2).
Metastatic hormone-sensitive prostate cancer (mHSPC)
Use of intensified triplet therapy (ADT plus docetaxel plus ARPI)
Two trials have demonstrated improved overall survival for the triplet combination of ADT plus docetaxel plus ARPI compared to the doublet of ADT plus docetaxel alone (14,15). There is, however, no randomized trial comparing the triplet combination with a doublet of ADT plus ARPI. Nevertheless, the use of triplet is encouraged by the guidelines, especially in case of synchronous high-burden disease. Subgroup analyses of ARASENS have also demonstrated benefit for triplet therapy in men with metachronous as well as low-burden disease (16). There was strong consensus (91 %) at our meeting that the burden of disease represents the most important clinical factor for decisions regarding the use of triplet therapy. In patients with low tumor burden, there is strong consensus (95 %) not to use triple therapy in the metachronous setting, and almost consensus (73 %) not to use it in the synchronous setting. Since many patients today have a PSMA PET for staging instead of conventional imaging, we asked the question if high tumor burden in PSMA PET should be equally treated as high tumor burden on conventional imaging. While 29 % accept PSMA PET results unequivocally, the majority (71 %) requests that high tumor burden in PSMA PET is only equal if morphological correlates for bone metastases (+/– visceral metastases) are detectable on conventional CT. Apart from disease burden, the timepoint of occurrence of metastatic disease (synchronous vs. metachronous) is also accepted as a possible risk factor since there is consensus (86 %) to apply triplet therapy in synchronous high-burden disease in the majority of patients, whereas only 36 % recommend this in metachronous high-burden patients, and 59 % would only apply triplet in selected patients in this situation.
Radiotherapy to primary tumor in the prostate in synchronous mHSPC
Several years ago, the STAMPEDE trial demonstrated that radiotherapy to the prostate was associated with a significant overall survival benefit in the subgroup of low volume synchronous mHSPC (17). Further analyses revealed that low volume was defined as up to 3 bone metastases and/or lymph node metastases only on conventional imaging (18). The population in the STAMPEDE study accrued before the use of ARPI in mHSPC was standard of care, questioning the contemporary value of this result. The study PEACE-1 also asked the question of radiotherapy to the primary prostate cancer, but in this study the ARPI abiraterone was also used (19). PEACE-1 could not replicate the overall survival benefit for low-burden mHSPC, but the results are controversially discussed due to the complex design of the study. At our meeting there was near consensus (74 %) to use radiotherapy to the prostate in addition to ADT plus ARPI therapy in patients with synchronous low-burden mHSPC on PSMA PET, whereas 13 % would opt for ADT plus ARPI, 9 % for RT plus ADT and 4 % for RT of the prostate alone. This is an interesting voting result both since clear data of a benefit for radiation to the primary tumor in the context of ADT plus an additional ARPI is lacking and also none of the trials have so far used PSMA PET for staging in this context.
Metastases directed therapy (MDT) in low-burden mHSPC
In men with low disease burden, the question often arises whether or not to use metastasis-directed therapy with surgery and/or stereotactic ablative body radiotherapy (SABR). So far there is still very scarce data for such an approach and no randomized data at all, nevertheless it is widely used also in Switzerland. Only two single randomized phase II studies (ORIOLE (20) and STOMP (21)) have been published, and they reported a benefit for using MDT in the metachronous setting for patients with up to 3 metastases with an improved progression free survival and delayed start of ADT therapy. At our meeting there was consensus (78 %) to use MDT in patients with synchronous low-burden mHSPC as found in a PSMA PET in addition to the standard therapy discussed above: 48 % would use MDT in patients with up to five metastases (bone and/or lymph node), 26 % in patients with up to three metastases (bone and/or lymph node) and 4 % in up to five lymph node metastases, while 22 % would not recommend MDT. In the situation of metachronous low-burden mHSPC on PSMA PET there was consensus (85 %) to administer ADT plus ARPI as systemic therapy and also consensus (87 %) to add some form of MDT in addition to the standard therapy: 61 % would apply MDT in case of up to five metastases (bone and/or lymph node), 22 % in up to three metastases (bone and/or lymph node) and 4 % in up to five lymph node metastases only, while 13 % do not routinely recommend MDT in this situation.
De-escalation strategies in mHSPC
The introduction of highly effective systemic therapy with ADT in combination with ARPI (abiraterone, enzalutamide, apalutamide, darolutamide) in the setting of mHSPC even in patients with very good prognosis on ADT alone (e.g. low-burden metachronous mHSPC) has led to discussions about the need for continued doublet therapy until progression to metastatic castration resistant prostate cancer (mCRPC) which in many cases results in year-long therapy associated with side effects and high cost. There are to date no published trials comparing continuous versus intermittent doublet therapy but the EORTC has recently set up a very large multinational randomized study investigating this question (EORTC 2238 De-escalate/PEACE-6 (22)). In clinical practice, many experts already use some form of intermittent therapy, often on patients’ request. The Swiss experts at our meeting reached a consensus (80 %) that an interruption of systemic therapy can be discussed at some point if patients achieve a deep remission, with PSA < 0.2 ng/ml: 25 % would discuss this option after a treatment period of 6–12 months, 50 % after 12–24 months and 5 % after 36 months of therapy. The main reason not to consider treatment interruption are features of aggressive prostate cancer (65 %, i.e. high-burden disease with low PSA levels at presentation, liver and/or osteolytic bone metastases, neuroendocrine features) or generally high-burden disease at presentation (13 %) whereas high level of PSA at presentation (0 %) or ISUP grade 4–5 (4 %) appear not relevant to the expert panel. In case of interruption the vast majority (89 %) would suspend systemic therapy entirely (i.e. ADT and ARPI) and there was strong consensus (90 %) to monitor the course clinically with PSA measurement and only recommend imaging in case of clear PSA dynamics (e.g. PSA-DT ≤ 3 months or PSA rise to > 5 ng/ml) and not on a regular schedule. Of note, the concept of treatment interruption has not yet been formally evaluated in randomized studies comparing this approach with the current standard of continuous combined therapy. A flow diagram for mHSPC is shown in (Fig. 3).
Metastatic castration-resistant prostate cancer (mCRPC)
Next generation sequencing (NGS) analysis and genetic counseling in patients with advanced prostate cancer
The choice of therapy in the mCRPC setting may depend on some molecular factors including DNA deficiency repair (DDR) alterations (including but not limited to BRCA1, BRCA2, ATM, PALB2, RAD51, CDK12, CHEK2, FANCA mutations), microsatellite instability (MSI) and potentially other rare molecular alterations. All panel members recommend NGS testing for advanced prostate cancer, 5 % already in case of high-risk localized disease, 45 % at diagnosis of mHSPC and 50 % at diagnosis of mCRPC. International guidelines recommend genetic counseling (and subsequent germline testing) for all patients with high-risk localized or metastatic prostate cancer (e.g. NCCN updated guideline 2024 (23). Testing should be done preferably on a biopsy from a metastasis, including lymph node biopsies from patients with N1 disease. When a metastatic biopsy is unsafe or unfeasible, a plasma circulating tumor DNA assay is an option, preferably collected during biochemical and/or radiographic progression in order to maximize the diagnostic yield. The majority of the Swiss expert panel (65 %) would recommend genetic counseling in case of pathogenic somatic mutations found in the NGS, 15 % would recommend it for all high-risk localized patient and 10 % each for mHSPC and mCRPC, respectively. This is in line with the Swiss guideline from 2021 (24).
First-line therapy in mCRPC without BRCA mutations
The choice of first-line therapy in patients with progression to mCRPC clearly depends on the previous systemic treatment that patients have received while being hormone-sensitive (mHSPC) and whether there is presence or absence of DDR alterations. In regard to DDR alterations, there was strong consensus (95 %) amongst the Swiss panel that only the presence of pathogenic BRCA mutations would qualify for specific targeted treatment with a PARP inhibitor. Therefore, the discussion of treatment selection in mCRPC will focus on the two groups of patients without or with BRCA mutations.
Some patients are still treated with ADT alone (+/– docetaxel) in the mHSPC setting, albeit likely a minority in Switzerland. There is strong consensus (95 %) that these patients should receive an ARPI when the tumor becomes castration resistant. In patients having received ADT plus ARPI in the mHSPC setting, there is strong consensus (91 %) to recommend docetaxel as first-line mCRPC treatment, only 9 % would opt for radionuclide therapy with 177Lu-PSMA. The latter recommendation is endorsed by the PSMAfore trial results that demonstrated improved radiographic PFS (rPFS) but not OS for 177Lu-PSMA in the mCRPC first-line setting in comparison to ARPI switch therapy in taxane-naïve men and is an option for men who are not fit for chemotherapy (25). In case patients received triplet therapy (ADT + ARPI + docetaxel) in the mHSPC setting the majority of experts (87 %) favor 177Lu-PSMA as first-line mCRPC therapy.
Therapy of mCRPC with BRCA mutations
As mentioned above, only the presence of BRCA mutations but not any other DDR alteration is considered relevant for treatment selection by the panel members. For patients with mCRPC who have not received an APRI in the mHSPC setting, all panel members agree (100 %) that the best first-line therapy consists of the combination of ARPI plus PARP inhibitor. This is based on three randomized clinical trials demonstrating clear benefit in this situation (26–28). All these trials did, however, only include a non-substantial number of patients being pretreated with ARPI making translation into a modern setting difficult. Indeed, when patients have received ARPI in the mHSPC setting, the panel reached a consensus (81 %) that single-agent PARP inhibitor therapy is the treatment of choice when progressing to mCRPC while only 14 % would add the PARP inhibitor to ongoing ARPI therapy and nobody is in favor of switching ARPI and adding a PARP inhibitor. In case of prior triplet therapy all panel members (100 %) recommend single agent PARP inhibitor as treatment of choice.
Use of radionuclide therapy with 177Lu-PSMA
A randomized phase 3 trial in patients with mCRPC and pretreatment with both ARPI and taxane demonstrated overall survival benefit for the use of LuPSMA using the compound 177Lu-PSMA-617 (29). Based on these data, there is strong consensus (95 %) to recommend 177Lu-PSMA in case of mCRPC with prior ARPI and taxane therapy meeting PSMA PET criteria for radionuclide therapy. The panel recommends (consensus 76 %) to monitor treatment effect of 177Lu-PSMA therapy with post-treatment SPECT and not to perform regular other imaging. In case of signs of response (clinical, PSA, imaging) after 2 cycles, the panels strongly recommend (94 %) to continue for a total of up to 6 cycles of 177Lu-PSMA provided that PSMA-based imaging shows remaining significant uptake, whereas a majority (70 %) would stop after 2 cycles if no remaining uptake is found. With regard to the use of PSMA radionuclide ligands other than 177Lu-PSMA-617 (used in the studies PSMAfore (25) and VISION (29)), the panel is in consensus (84 %) that other compounds (namely PSMA-I&T, 67 %) should be considered equivalent. Finally, 177Lu-PSMA has thus far only demonstrated advantage in the setting of mCRPC. While trials are ongoing using 177Lu-PSMA in earlier settings, there is strong consensus (94 %) to not recommend the use of 177Lu-PSMA in mHSPC outside of clinical trials. Fig. 4 shows the flow diagram of mCRPC therapy.
Selected miscellaneous topics
Choice of androgen deprivation therapy (ADT)
It is well known that androgen deprivation can lead to increased morbidity and mortality from cardiovascular events, especially in the first 6 months after starting ADT. There is evidence from subgroup analyses that LHRH antagonists (degarelix and relugolix) might be associated with a lower risk of major adverse cardiovascular events (MACE) including myocardial infarction, stroke, or death from any cause. However, patients with a recent history of MACE are generally excluded from clinical trials limiting the evidence. A recent trial using the oral LHRH antagonist relugolix (HERO (30)) demonstrated a lower incidence of MACE with relugolix compared to leuprolide (2.9 % vs. 6.2 %; hazard ratio HR 0.46) in a preplanned analysis, while a prospective randomized trial comparing degarelix to leuprolide (PRONOUNCE (31)) failed to show any difference in the primary endpoint of MACE. Nevertheless, 86 % of panel members would recommend using a LHRH antagonist instead of an agonist for patients with a recent history of MACE.
Management of ADT-induced hot flushes
Almost all men undergoing testosterone-ablative therapy (irrespective of method) experience some degree of hot flushes. These can be very cumbersome for some men, and sometimes even debilitating. Some non-medical lifestyle interventions have proven to be beneficial, including regular exercise and acupuncture. Such non-medical interventions are also recommended by the Swiss experts with 16 % favoring acupuncture, 21 % exercise and 63 % recommending both options. Cyproterone acetate appears to be the most used medical intervention against hot flushes with two-thirds of panel members (67 %) indicating experience, whereas one-third prefers venlafaxine (33 %). The novel agent fezolinetant (neurokinin-3 antagonist), that has a meaningful impact in the treatment of hot flushes in women, is so far not yet in use, but trials with this agent are ongoing.
Bone health for men on androgen deprivation therapy
It is well established that ADT significantly reduces bone mineral density, and many elderly men already have osteopenia or even osteoporosis before starting treatment. Guidelines therefore recommend checking for pre-existing bone mineral density loss using osteodensitometry and/or to assess risk of bone fracture using the FRAX-score. As discussed and published in a former Swiss consensus meeting (32) antiresorptive therapy to prevent or treat osteoporosis and its associated complications is indicated in men undergoing ADT (indications: T-score < –1.5, FRAX-score > 20 % or risk for hip fracture > 3 %). The antiresorptive therapy can be done by either using denosumab 60mg every 6 months (recommended by 82 %), once a year with zoldedronic acid (recommended by 18 %) or using an oral weekly bisphosphonate. The planned duration of ADT or possible intermittent schedules should be considered when choosing the antiresorptive therapy since for denosumab a rebound effect has been described leading to increased risk of osteoporotic fractures in case of stopping it. Guidelines therefore recommend administering one or two doses of zoledronic acid to prevent rebound-associated fractures before discontinuation of denosumab (33). Two-thirds (67 %) of the Swiss panel also follow this recommendation (55 % for the majority and 12 % for selected patients).
Arnoud J. Templeton 1, Vérane Achard 2, Dilara Akhoundova 3, Irene A. Burger 4, Daniel Eberli 5, Daniel Engeler 6, Andreas Erdmann 7, *Stefanie Fischer 8, Rainer Grobholz 9, *Anja Lorch 10, Philip Niederberger 11, Aurelius Omlin 12, Alexandros Papachristofilou 13, Lukas Prause 14, Katharina Reichel 15, Cyrill A. Rentsch 16, Mohamed Shelan 17, Frank Stenner 18, Petros Tsantoulis 19, *Ursula Vogl 20, Deborah Zihler 21, Daniel Zwahlen 22, Richard Cathomas 23
* These co-authors could not attend the consensus meeting in person.
1 Medical Oncology, St. Claraspital, Basel, Switzerland, St. Clara Research Ltd., Basel, Switzerland, and Faculty of Medicine, University of Basel, Basel, Switzerland
2 Department of Radiotherapy, Institut Bergonié, Bordeaux, France and University of Geneva, Geneva, Switzerland
3 Department of Medical Oncology, Inselspital, Universitätsspital, University of Bern, Bern, Switzerland
4 Department of Nuclear Medicine, Kantonsspital Baden, affiliated Hospital for Research and Teaching of the Faculty of Medicine
of the University of Zurich, Baden, Switzerland
5 Department of Urology, Universitätsspital Zürich, Zurich, Switzerland
6 Department of Urology, Kantonsspital St. Gallen, St. Gallen, Switzerland
7 Department of Urology, Luzerner Kantonsspital, Luzern, Switzerland
8 Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland
9 Department of Pathology, Kantonsspital Aarau, Aarau, Switzerland and Faculty of Medicine, University of Zurich, Zurich, Switzerland
10 Medical Oncology and Hematology, Universitätsspital Zürich, Zurich, Switzerland
11 Department of Oncology, Luzerner Kantonsspital, Luzern, Switzerland
12 Onkozentrum Zurich, University of Zurich and Tumorzentrum Hirslanden Zurich, Switzerland
13 Department of Radiation Oncology, Universitätsspital Basel, Basel, Switzerland
14 Department of Urology, Kantonsspital Aarau, Aarau, Switzerland
15 Department of Oncology, Stadtspital Triemli, Zurich, Switzerland
16 Department of Urology, Universitätsspital Basel, Basel, Switzerland
17 Department of Radiation Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
18 Medical Oncology and Hematology, Universitätsspital Basel, Basel, Switzerland
19 Medical Oncology and Hematology, Hôpital Universitaire de Genève, Geneva, Switzerland
20 Oncology Institute of Southern Switzerland (IOSI), EOC, Bellinzona, Switzerland
21 Tumor- und Brustzentrum Ostschweiz, Rapperswil-Jona, Switzerland
22 Department of Radio-Oncology, Kantonsspital Winterthur, Winterthur, Switzerland
23 Division of Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland
History
Manuscript received: 06.02.2025
Accepted after revision: 11.03.2025
Medical Oncology
Claraspital Basel
4058 Basel
arnoud.templeton@claraspital.ch
Division of Oncology/Hematology
Kantonsspital Graubünden
7000 Chur
richard.cathomas@ksgr.ch
P, personal compensation; I, compensation to institution
Arnoud J. Templeton has received has received honoraria for consulting or participation in advisory boards from Astellas (I), Bayer (I), BMS (I), Janssen (I), Ipsen (I), Merck (P), MSD (P, I), Pfizer (I), Sandoz (I), and SAKK (P); he has received honoraria for lectures and presentation from Bayer (I), and Janssen (P); he has received conference/travel support from Roche (P), and Orion Pharma (P).
Vérane Achard has no conflicts of interest.
Dilara Akhoundova has received honoraria for lectures and presentations from BMS (I), Janssen (I), and Bayer (I); she has received conference/travel support from Janssen (P), Ipsen (P), and Bayer (P).
Irene A. Burger has received research grants and speaker honoraria from GE Healthcare (I, P) and Bayer (I), research grants from Swiss Life (I), Vontobel foundation (I) and speaker honoraria from Novartis (I, P), Janssen (I) and Astellas Pharma AG (I). She has participated in advisory boards for GE Healthcare (I), Novartis (I) and Bayer (I) and received conference/travel support from Bayer (P) and Novartis (P).
Daniel Eberli has no conflicts of interest.
Daniel Engeler has no conflicts of interest.
Andreas Erdmann has no conflicts of interest.
Stefanie Fischer has received honoraria from Johnson&Johnson (I), Conference/Travel support from Bayer (P), Research support from Astelllas (I) and MSD (I) and consulting fees from Amgen (I)
Rainer Grobholz has no conflicts of interest.
Anja Lorch has received honoraria for consulting or participation in advisory boards from Astellas (P), Astra Zeneca (P), Bayer (P), BMS (P), Eisai (P), Ipsen (P), Janssen (P), Merck (P), MSD (P), Novartis (P), Pfizer (P), Roche (P). She has received conference/travel support from Ipsen (P), Janssen (P), and Bayer (P).
Philip Niederberger has no conflicts of interest.
Aurelius Omlin has received consulting fees from: Abbvie (I), Accord (I), Advanced accelerator applications (AAA) (I), Astra Zeneca (I), Astellas (I), Bayer (I), Janssen (I), Monrol (I), Merck (I), MSD (I), Myriad (I), Novartis (I), Pfizer (I), Roche (I); he has received travel support from Astellas (P), Bayer (P), Janssen (P).
Alexandros Papachristofilou has no conflicts of interest.
Lukas Prause has received consulting fees from Astellas (I), Janssen (I), Bayer (I), Astra Zeneca (I); he has received travel support from Bayer (I).
Katharina Reichel has received consulting fees from Astellas (P), Bayer (P), BMS (P), Janssen (P), Merck (P), MSD (P), and Novartis (P); she has received travel grants from Bayer (P), Janssen (P), and Ipsen (P).
Cyrill Rentsch has no conflicts of interest.
Mohamed Shelan has no conflicts of interest.
Frank Stenner has received fees from Bayer (I), BMS (I), Janssen (I), Merck (I), MSD (I); he has received travel grants from BMS (P), and Roche (P).
Petros Tsantoulis has received fees from Roche (P), Sanofi (P), MSD (P), Bayer (P), Astellas (P), BMS (P), Pfizer (P), Johnson & Johnson (P), Ipsen (P), Novartis (P), and Merck (P); he has received conference/travel support from Lilly (P), Ipsen (P), Johnson & Johnson (P), Bayer (P), and Sanofi (P).
Ursula Vogl has received speaker or consultancy honoraria from Astellas (I, P), Astra Zeneca (I), Bayer (I), Institutional , European School of Oncology (ESO) (I) The hHealthb Book Times (I, P) Janssen Cielag (I), Merck (I), MSD (I), Novartis AAA (I), Oncology Compass (I), SAKK (I), SAMO (I, P), travel grants from Astra Zeneca, Janssen, Merck and Ipsen (P), Grant Funding from Fond’Action Research Grant (I). She is SAKK PG UG president and Editor in Chief of the Health Book Times.
Deborah Zihler has received fees for consulting or advisory roles from Astellas (P), Bristol Myers Squibb (P), Merck & Co. (P), Kenilworth , NJ ((P), Novartis (P), Orion Pharma (P), Merck KGaA (P). She has received medical education support from Janssen-Cilag (P).
Daniel Zwahlen has no conflicts of interest.
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 honoraria 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).
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